Dose-limiting Toxicity Research Articles

Abstract CT089: A phase 1 multi-center, open label, dose escalation study to evaluate the safety, pharmacokinetics (PK) and anti-tumor activity of T-1301, a novel small molecular multi-target kinase inhibitor, in patients with advanced solid tumors

Abstract Background: T-1301 is a novel small molecule multi-target kinase inhibitor, it also exhibited potent inhibitory activity against both wild type and mutant forms of various kinases, i.e., ABL1, FLT3, c-KIT, PDFGRA, RET, and TRKA. In in vitro studies, T-1301 effectively inhibited growth of acute myeloid leukemia (AML) as well as gastrointestinal stromal tumor (GIST) cells carrying mutations that are resistant to KIT-targeting tyrosine kinase inhibitors (TKIs) in clinical use. In animal studies, tumor regressions were observed in AML and GIST xenograft models, while growth inhibition were observed in various other types of solid tumor models. Method: This is an open label, multi-centered Phase 1 dose escalating study (NCT05156203). The primary objectives are to establish the maximal tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to assess the safety and tolerability of T-1301. The secondary objectives are to evaluate the pharmacokinetics (PK) and therapeutic response after receiving treatment. Eligible Patient should have histologically and cytologically confirmed advanced solid tumors (including lymphoma) with measurable or evaluable target lesion(s) per RICEST v1.1 and refractory to or without standard treatments, ECOG performance status 0-1, and adequate organ function. The dose escalation begins with accelerated titration and switch to the Bayesian Optimal Interval (BOIN) design when either one of the following events is observed in Cycle 1: the first instance of DLT, or any Grade 2 or higher drug-related adverse event (AE) in any patient. Then, at least 2 additional subjects are treated at the current dose level and the dose escalation will follow the Bayesian Optimal Interval (BOIN) design with cohorts of size 3-6.T-1301 is orally administered daily in a 28-day cycle (a 21-day consecutive dosing followed by a 7-day rest). The dosing schedule is once daily (QD) at the initial dose level and could be QD or twice daily starting with the second dose level according to the safety review committee (SRC) decision after reviewing the safety and PK data from each dose level. AEs are assessed according to CTCAE v5.0 and occurrence of dose limiting toxicity (DLT) is determined during the first cycle of treatment. The safety findings are reviewed by the SRC, which will determine the MTD and RP2D. Tumor response evaluation is performed after 2 cycles of treatment and assessed according to RECIST v1.1 criteria. For those who benefit from the study medication after 2 treatment cycles, intra-subject dose escalation for multiple times is allowed in extension study period. Patient recruitment began in December 2021 and is ongoing in Taiwan. Citation Format: Jen-Shi Chen, Ming-Huang Chen, Yi-Chang Liu, Wen-Chi Chou, Nai-Jung Chiang, Hui-Ching Wang, Ta-Sen Yeh, Shih-Feng Cho, Cheng-Hsu Wang, I-Fang Lee, Li-Tzong Chen. A phase 1 multi-center, open label, dose escalation study to evaluate the safety, pharmacokinetics (PK) and anti-tumor activity of T-1301, a novel small molecular multi-target kinase inhibitor, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT089.

Abstract CT136: Phase Ib study of siltuximab and spartalizumab in advanced pancreatic cancer

Abstract Background: Pancreatic adenocarcinoma (PDAC) is an aggressive malignancy with dismal prognosis. Most patients present with advanced stages. Heightened levels of serum interleukin-6 (IL-6) are associated with carcinogenesis, immune suppression, and poor prognosis in PDAC. Preclinical data of dual inhibition of IL-6 and programmed death ligand-1 (PD-L1) facilitates CD8+ T-cell migration into pancreatic tumors and was effective in controlling tumor growth in syngeneic and genetically engineered PDAC mouse models. Siltuximab (Sil) is a chimeric monoclonal antibody which targets the IL-6 molecule specifically. Spartalizumab (Sparta) is a high-affinity ligand-blocking humanized IgG4 antibody against the PD-1 receptor. We developed a phase Ib/II trial to evaluate the safety, immunogenicity and preliminary antitumor activity of Sil and Sparta in metastatic PDAC (mPDAC). Methods: Patients (pts) with mPDAC who have progressed on at least one line of systemic chemotherapy were eligible for the trial. Other selected inclusion criteria were ≥18 years of age, ECOG PS 0-1 and measurable disease per RECIST v1.1. The phase Ib trial design is standard 3+3, with a primary endpoint of recommended phase II dose (RP2D). An additional 24 patients were planned for an expansion cohort. Sil was administered at escalating dose levels of 6 mg/kg (DL1) and 11 mg/kg (DL2), in combination with Sparta at 300 mg IV on day 1 of each 21-day cycle. Key secondary endpoints included overall response rate (ORR = CR + PR), progression-free survival (PFS) and overall survival (OS). Results: We enrolled 4 patients on DL1 and escalated to DL2/RP2D in the absence of a dose limiting toxicity (DLT). A total of 31 patients were subsequently treated at the RP2D (escalation + expansion). The median age was 68 years, 42% were male. Majority were White (63%) and 20% were Black. About 43% had head of pancreas primary tumors and 86% had liver involvement. The median number of lines of prior therapy was 3 (range 1-4). There was no objective response among the 4 patients on DL1; 1 had stable disease (SD) for 11 weeks as best response. 17 of 31 patients on RP2D had only a baseline assessment and came off study for progression of disease, prior to follow-up imaging assessment for response evaluation. Of the 14 RP2D patients with a follow-up assessment, ORR was 0% (3 were SD and 11 had progression of disease (PD) as best response), mPFS - 2.2 mos (95% CI: 1.9, 2.6), mOS - 5.5mos (95% CI: 2.8, 6.5). Treatment related adverse events (TRAEs) of any grade included fatigue (23%), anemia (18%), and increased liver enzymes (9.5%). There were no grade 4-5 TRAEs. Conclusions: The combination Sil/Sparta had an acceptable safety profile but did not elicit responses in advanced PDAC pts. Correlative studies using paired biopsies and blood are ongoing to determine how dual IL-6/PD-1 blockade impacts stromal and immune biomarkers in relationship to the clinical outcome measures. Funding and medications for the study were provided by Novartis and Recordati Rare Diseases Inc (NCT04191421) and NIH/NCI (R21CA266088). Citation Format: Olatunji B. Alese, Olumide Gbolahan, Kathleen M. Coleman, Yichun Cao, Sujata Kane, Sarah Craven, Emily Greene, Natalie Horvat, Andrew McDonald, Walid L. Shaib, Christina S. Wu, Mehmet Akce, Maria Diab, Jeffrey M. Switchenko, Gregory B. Lesinski, Bassel F. El-Rayes. Phase Ib study of siltuximab and spartalizumab in advanced pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT136.

Abstract CT119: Safety and efficacy of HS-10370 in KRAS G12C-mutated solid tumors including non-small cell lung cancer (NSCLC)

Abstract Background: KRAS G12C mutation occurs in ~13% of NSCLC and up to 4% of other solid tumors. HS-10370 is a selective, covalent, orally bioavailable KRAS G12C inhibitor. We conducted a first-in-human phase I trial to evaluate the dose-limiting toxicity (DLT), safety, tolerability, pharmacokinetics, and efficacy of HS-10370 in patients (pts) with advanced solid tumors bearing KRAS G12C mutation. Methods: In a phase I study HS-10370-101 (NCT05367778), patients of advanced or metastatic solid tumors with measurable disease were recruited. HS-10370 monotherapy was given at oral doses of 200~1600 mg QD until disease progression, intolerance, or withdrawal from consent. Rolling 6 was applied as the dose escalation schedule in this phase I dose escalation trial. The primary objectives of the dose escalation part was safety and tolerability. The secondary objectives included pharmacokinetics (PK) profile and efficacy. Results: As of Dec 15th, 2023, 55 patients with advanced solid tumors were enrolled in this study, including 49 patients with KRAS G12C mutation. Of the 49 patients, 43 were with NSCLC, 5 with colon cancer, and 1 with pancreatic cancer. Safety: No dose-limiting toxicity was observed, neither maximum tolerated dose (MTD) been identified. Treatment-emergent adverse events(TEAEs) occurred in 87.3% of the treated patients (48/55), the most common TEAEs (≥10%) were AST increase (29.1%, 16/55), ALT increase (29.1%, 16/55), anemia(27.3%, 15/55) , diarrhea (25.5%, 14/55), weight gain (18.2%, 10/55), decreased appetite (14.5%, 8/55), hypoproteinemia (12.7%,7/55), nausea(12.7%,7/55), fatigue(14.5%, 8/55) and rash (12.7%, 7/55). The TEAEs ≥Grade 3 occurred in 27.3% patients (15/55). TEAEs leading to dose interruptions and dose reductions were reported in 18.2% patients (10/55) and 7.3% patients (4/55), respectively. Efficacy: Of the 49 patients with KRAS G12C mutant status, 24 had partial response (PR) and 20 had stable disease (SD). The confirmed objective response rate (ORR) and disease control rate (DCR) were 49.0% and 89.8% respectively. Objective responses were observed in patients received 400mg QD or above. In patients with KRAS G12C mutant NSCLC who received more than or equal to 400mg daily dose, the confirmed ORR and DCR were 51.2% (21/41) and 95.1% (39/41), respectively. Of the same subpopulation, the median duration of response was not reached (5.4, NA). Meanwhile, the median progression-free-survival (PFS) was 11.3 month (6.1, NA), with the 6-months PFS rate 75% and the 9-months PFS rate 63.6%. Responses were also observed in patients with colon cancer and pancreatic cancer. Conclusions: HS-10370 was well tolerated and showed inspiring antitumor activities in KRAS G12C mutated advanced solid tumors, especially in NSCLC. Citation Format: Xiaorong Dong, Xiangjiao Meng, Yan Zhang, Yan Wang, Jianhua Chen, Liang Han, Qiming Wang, Zhong Lin, Hongying Wei, Siheng Lin, Chuan Li, Qiong Wu. Safety and efficacy of HS-10370 in KRAS G12C-mutated solid tumors including non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT119.

Abstract CT080: A phase I study of CPI-613 (devimistat) in combination with chemoradiation in patients with pancreatic ductal adenocarcinoma

Abstract Background: Local tumor progression is a cause of significant mortality and morbidity in patients (pts) with inoperable pancreatic ductal adenocarcinoma (PDAC). Effective approaches to achieve durable local control are urgently needed. Metabolic reprogramming and enhanced mitochondrial function are known contributors to chemo- and radio-resistance in PDAC. CPI-613, a lipoic acid analog that selectively inhibits components of the Krebs cycle in tumors, showed promising preclinical synergy in combination with gemcitabine and radiation (gem-RT). We initiated a phase I study (NCT05325281) to determine the maximum tolerated dose (MTD) of CPI-613 when used with gem-RT. Here, we present the results from the first cohort of this study. Methods: Adult pts with inoperable PDAC that, by institutional multidisciplinary review, were considered to benefit from definitive local control of the primary tumor were eligible for the study. CPI-613 was administered once weekly by intravenous infusion over ~ 2 hours at a starting dose of 500 mg/m2 and dose-escalated using a Bayesian optimal interval design. Gemcitabine was given once weekly at 400 mg/m2 and RT at 45-54 Gray (Gy) in 25-30 fractions. Results: By Jan 7, 2024, six pts were enrolled, and five completed the treatment and dose-limiting toxicity (DLT) period. Table 1 describes the characteristics of these five pts. As CPI-613 was not associated with any additional toxicities, specifically cytopenia(s), after the first two pts, the study protocol was amended to allow CPI-613 to be administered on weeks gemcitabine was held for cytopenia(s). The study, therefore, enrolled five pts in the first cohort. All pts received ≥ 16 weeks of systemic chemotherapy with at least stable disease per imaging prior to enrollment. None of the pts experienced DLTs. All treatment-related toxicities were expected from gem-RT, unrelated to CPI-613, and manageable. The trial is currently enrolling pts in the second cohort (CPI-613 dose of 1000 mg/m2). Conclusions: CPI-613 combined with gem-RT was safe and well tolerated at a dose of 500 mg/m2. Recruitment to the study is ongoing to determine the MTD of CPI-613 in combination with gem-RT. Table 1. Characteristic of Patients Sex Race Age ECOG Stage Prior chemotherapy Chemotherapy duration (weeks) M W 67 1 LA FFX 16 M W 64 1 LA GnP 35 M W 73 1 BR* GnP 16 M B 71 1 LA GnP 27 M W 80 1 Oligometastatic** GnP 18 * Medically inoperable ** Two lung metastases treated with stereotactic body radiation therapy (SBRT); BR: Borderline resectable; B: Black; FFX: FOLFIRINOX; GnP: Gemcitabine/Nab-paclitaxel; LA: Locally advanced. M: Male; W: White Citation Format: Mandana Kamgar, Husain Yar Khan, Amro Aboukameel, Sahar F. Bannoura, Brian Y. Chung, Aniko Szabo, Yiwei Li, Mohammed Najeeb Al Hallak, Philip A. Philip, Ben George, Kathleen K. Christians, Douglas B. Evans, Susan Tsai, Beth Erickson, John M. Goldberg, Asfar S. Azmi, William A. Hall. A phase I study of CPI-613 (devimistat) in combination with chemoradiation in patients with pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT080.

Abstract CT182: Oncolytic virus CF33-hNIS for the treatment of advanced cancer

Abstract Background: CF33-hNIS is a novel vaccinia virus engineered with the human sodium-iodide symporter (hNIS) gene. CF33-hNIS selectively replicates in tumor cells and promotes anti-tumor immunity. Here, we report results on a first-in-human phase 1 dose escalation study of CF33-hNIS, administered intratumorally (IT) or intravenously (IV) in adult patients with metastatic or advanced solid tumors (MAST). Methods: The MAST study is evaluating the safety of CF33-hNIS administered IT or IV, alone or in combination with pembrolizumab in patients with advanced or metastatic solid tumors with ≥ 2 prior lines of therapy (NCT05346484). CF33-hNIS is administered in 21-day cycles on C1D1 and C1D8, then D1 of each cycle thereafter. Pembrolizumab begins C2D1 for the combination groups and is administered Q3W. The study consists of two parts. Part 1 follows a 3+3 dose escalation scheme independent of each route of CF33-hNIS administration (IT and IV) and for each therapy regimen (monotherapy and combination therapy) with up to 7 dose levels of CF33-hNIS ranging from 8.6x105 to 3.0x109 PFU. Part 2 is a cohort expansion in select indications at the optimal dose. The co-primary endpoints are safety and identification of the recommended phase 2 dose. Secondary endpoints include objective response rate according to RECIST v1.1 and iRECIST, and assessment of viral replication in tumor lesions via Single-Photon Emission Computerized Tomography (SPECT). Results: As of Dec 2023, 36 patients have been treated in Part 1 of the study with a median age of 59 (range 23-81). Twenty-two (61%) patients were heavily pretreated with ≥3 prior lines of systemic therapy, and 14 (39%) received prior treatment with checkpoint blockade. Treatment-related adverse events consisted predominantly of ‘flu-like’ symptoms, such as grade 1/2: fatigue (31%), pyrexia (22%), and chills (14%). No dose-limiting toxicities have occurred. The highest dose treated to date is 1.1x108 PFU by IT and IV delivery; dose escalation continues. In the IT cohorts (14 patients), 7 of 15 (47%) injected lesions had a reduction in tumor burden, three lesions were completely eradicated. Three patients (21%) had an objective response: one complete response by iRECIST in a patient with cholangiocarcinoma; and two partial responses in patients with melanoma by RECIST. In IV cohorts (17 patients), 53% of patients achieved stable disease as their best response. Patients who received prior checkpoint blockade therapy derived clinical benefit with and without pembrolizumab. Viral replication, assessed by SPECT was higher in patients that saw a reduction in tumor burden. Immunological changes in peripheral blood and tumor biopsies will be presented. Conclusions: CF33-hNIS alone or in combination with pembrolizumab is a safe treatment option for advanced cancer patients. Encouraging efficacy has warranted advancement to part 2 of this study with a cohort expansion of patients with cholangiocarcinoma and other tumor types. Citation Format: Daneng Li, Anthony F. Shields, Hirva Mamdani, Patrick Travis, Gavin Wright, Wallace Akerley, Alex Spira, Gregory Daniels, Jaime Merchan, Abhijeet Kumar, Emerson Lim, Colt Egelston, Oscar Flores, Stanley Hamilton, Janet Austria, Amanda Seiz, Sharon Yavrom, Seymour Fein, John Byon, Paul Woodard, Grey A. Wilkinson, Jennifer Leddon. Oncolytic virus CF33-hNIS for the treatment of advanced cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT182.

Abstract CT139: Immunological activity of oncolytic adenovirus encoding TNFα and IL-2 (TILT-123) in combination with pembrolizumab in platinum resistant or refractory ovarian cancer patients

Abstract Background TILT-123 (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is a serotype chimeric dual safety device oncolytic adenovirus armed with tumor necrosis factor alpha and interleukin-2. It was designed to improve efficacy of T-cell therapies such as immune checkpoint blockade or adoptive cell transfer. We present biological and immunological endpoints from an open-label phase 1 dose escalation study of TILT-123 in combination with anti-PD-1 pembrolizumab in platinum resistant or refractory ovarian cancer patients. Experimental procedures In this dose escalation trial (NCT05271318), patients were first injected with an intravenous (i.v.) dose of TILT-123 ranging from 3x1011 to 4x1012 virus particles (VP), followed by five intratumoural (i.t.) or intraperitoneal (i.p.) injections ranging from 1x1011 to 5x1011 VP. Patients also received intravenous injections of 200 mg pembrolizumab every three weeks starting 36 days after the first dose of TILT-123. The primary endpoint was safety, while efficacy by RECIST1.1 was a secondary endpoint. Collection of tumor biopsies, circulating immune cells, serum, saliva, urine and feces enabled multi-omic evaluation of mechanism of action and identification of predictive biomarkers. Summary of data As of January 2nd 2024, 15 patients received trial therapy. No dose-limiting toxicities were observed and the most frequent AEs associated with therapy included chills and nausea (>10% of patients). Stable disease by RECIST 1.1 was seen in 67% in 12 evaluable patients. TILT-123 replication was detected in both injected and non-injected tumors as assessed by qPCR and anti-hexon IHC. Multiplex immunofluorescence demonstrated induction of robust immunological activity in both injected and non-injected tumors, including significant increase in granzyme B+, PD-1+ CD4+ and CD8+ T cells as well as PD-1+ NK cells. Baseline intratumoral CD4+, FOXP3+ regulatory T cells were not associated with clinical response. Tertiary lymphoid structures and lymphoid aggregates were identified in patients showing long term disease control. Low to medium titers of neutralizing antibodies against 5/3 chimeric adenovirus were detected in 57% of patients at baseline and were not a predictive factor of disease control. No patients had high titers at baseline. Conclusion TILT-123 in combination with anti-PD-1 pembrolizumab was safe and resulted in disease control in both platinum resistant and refractory ovarian cancer patients. Analysis of biological samples revealed insights into mechanism of action, including an immune profile predictive of clinical response. These results, together with those from four other trials (NCT04695327, NCT04217473, NCT06125197 and NCT05222932) set the stage for continued clinical evaluation of TILT-123. Citation Format: James H. Clubb, Matthew S. Block, Johanna Mäenpää, Santeri Pakola, Lyna Haybout, Dafne C. Quixabeira, Tatiana Kudling, Mirte van der Heijden, Elise Jirovec, Tuomo Alanko, Daniel A. Adamo, Susan Ramadan, Jorma Sormunen, Juha Kononen, Julia W. Cohen, Nadena Singh, John Goldfinch, Suvi Sorsa, Riikka Havunen, Claudia Kistler, João M. Santos, Víctor Cervera-Carrascon, Akseli Hemminki. Immunological activity of oncolytic adenovirus encoding TNFα and IL-2 (TILT-123) in combination with pembrolizumab in platinum resistant or refractory ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT139.

Abstract CT154: Phase 1/2 clinical trial of JIN-A02, a 4th generation EGFR-TKI, in patients with 3rd generation EGFR-TKI resistance in EGFR mutated advanced/metastatic non-small cell lung cancer (NSCLC)

Abstract Background: Epidermal growth factor receptor (EGFR) mutations are the most common driver mutations in NSCLC. EGFR tyrosine kinase inhibitors (TKIs) are the recommended front-line option for EGFR-mutant advanced NSCLC patients, but patients invariably develop acquired resistance and face disease progression. JIN-A02, a 4th generation EGFR-TKI intended for oral administration, selectively and reversibly binds to EGFR mutations, including the C797S and/or T790M mutation that causes resistance to 3rd generation of EGFR-TKIs. Pre-clinical studies with EGFR C797S and/or T790M mutated cell lines showed that JIN-A02 can inhibit cell growth in a dose dependent manner and has a high degree of selectivity over wild-type EGFR. In vivo studies showed that administration of JIN-A02 dose-dependently inhibited tumor growth in the C797S+ xenograft mice model. Moreover, JIN-A02 shown to penetrate blood-brain barrier and exhibit anti-tumor activity in an intracranial tumor model. The strong potency and high selectivity of JIN-A02 for mutant EGFR may offer improved therapeutic window in the clinical setting vs available EGFR-TKIs. Methods: JIN-A02 is being evaluated in this Phase 1/2, multicenter, an open-label trial (NCT05394831) for subjects with advanced NSCLC harboring C797S and/or T790M mutation as a monotherapy. The primary object of this study is to assess safety, tolerability, pharmacokinetics, and anti-tumor effect for determining the recommended phase 2 dose (RP2D) of JIN-A02. The inclusion criteria are that the subject (≥ 18 years) must have an advanced or metastatic NSCLC showed progress disease (PD) after receiving approved standard EGFR-TKI therapies and/or platinum-based anticancer chemotherapy is allowed up to 1 time after using EGFR-TKI treatment with ECOG status 0 or 1. Before enrollment in the study, the EGFR mutation status is determined using either tumor tissue and/or plasma ctDNA. This study comprises three parts, dose escalation (Part A), dose exploration (Part B), and dose expansion (Part C). In Part A, dose escalation, comprised of 5 cohorts ranged from a starting dose of 12.5 mg P.O, QD to a top dose of 150 mg P.O, QD with every three subjects, is carried out where the maximum tolerated dose (MTD) is evaluated in subjects with 28-day cycles. Dose-limiting toxicities (DLT) are evaluated for 21 days. In Part B, dose exploration is carried out to evaluate the safety of JIN-A02 further and to determine the RP2D using 2 preliminary effective dose levels from Part A in subjects. In Part C dose-expansion study, subjects (n=36 for each cohort) are divided into 5 different cohorts based on the EGFR mutation (both or single positive of C797S and T790M), and the anti-tumor activity of JIN-A02 is evaluated according to RECIST v1.1 at RP2D. Citation Format: Sun Min Lim, Byoung Chul Cho, Ji Youn Han, Sang We Kim, Ki Hyeong Lee, Misako Nagasaka, Anna Jo, Ethan Seah, Choonok Kim, Thanyanan Reungwetwattana. Phase 1/2 clinical trial of JIN-A02, a 4th generation EGFR-TKI, in patients with 3rd generation EGFR-TKI resistance in EGFR mutated advanced/metastatic non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT154.

Abstract CT181: First-in-human phase I of anti-VISTA monoclonal antibody W0180 with and without anti-PD-1 pembrolizumab in patients with locally advanced or metastatic solid tumors

Abstract Background: V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an immune checkpoint regulator highly expressed on myeloid cells. VISTA has been shown to maintain tumor microenvironment (TME) in an immunosuppressive state. Its expression is reported as a resistance mechanism to immune checkpoint blockers, making it an attractive target for cancer treatment. Preclinical data showed that VISTA blockade mediates antitumor activity by activating the antitumor immune response and is enhanced in combination with anti-PD-1. W0180 is a humanized, Fc competent, IgG1 antibody targeting VISTA with high affinity. This study investigates W0180 with/without pembrolizumab (pembro) in patients (pts) with solid tumors. Methods: Pts initially received W0180 monotherapy in dose escalation (3.5-600 mg weekly (QW)). Following evaluation of the first 3 dose levels in monotherapy, dose escalation of W0180 (60 to 300 mg QW) in combination with pembro (200 mg Q3W) started in pts treated with prior anti-PD-(L)1. Objectives were to characterize safety and tolerability of W0180, determine RDE and PK/PD on blood and paired tumor biopsies. Results: By October 2023, 33 pts were treated in dose escalation, 24 pts with W0180 monotherapy and 9 pts with W0180 + pembro. Two dose-limiting toxicities were observed, Grade 2 subacute cerebral infarction and Grade 3 infusion related reaction (IRR). Overall, 33 pts experienced ≥1 treatment-emergent AE (TEAE). Most common TEAEs were IRR (32/33), fatigue (14/33), and anemia (11/33). Grade 3/4 TEAEs occurred in 23 pts, neutropenia (6/23) and anemia (6/23) were the most common. There was no treatment-related death. 6 (18%) pts discontinued due to AEs. Following the observation of Grade 3 arterial thromboembolism (n=1) and Grade 2 subacute cerebral infarction (n=1), eligibility criteria were amended to require adequate lipid profile, troponin and exclude pts with history of arterial thrombotic events and current smoking. W0180 PK was nonlinear with a rapid clearance at 3.5-600 mg doses. No objective response was observed but 5 pts had stable disease (SD) lasting for >16 weeks. One pt with appendix cancer treated at 600mg monotherapy had SD for >15 months. One pt with head and neck cancer treated at 300mg in combination had SD for 13 months. Biomarkers data suggested evidence of PD effect with a trend for dose response through sustained increase of proliferative CD8+ T-cells in blood at the highest W0180 exposures and increased density of tumor-infiltrating lymphocytes in 10 out of 16 pts. These changes were independent of tumor VISTA expression level and correlated to high PD-L1 expression (CPS>5) for 4 pts at baseline. Conclusions: Analysis is ongoing to assess the RDE of W0180 + pembro and collect additional evidence of proof of mechanism in pts with solid tumors. NCT04564417 Citation Format: Carlos Gomez-Roca, Stéphane Champiat, Philippe Cassier, David Jegou, Marie Primard, Aurélie Pétain, Geneviève Gueguen-Dorbes, Claire Fabre, Ignacio Melero, Aurélien Marabelle. First-in-human phase I of anti-VISTA monoclonal antibody W0180 with and without anti-PD-1 pembrolizumab in patients with locally advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT181.

Abstract CT002: CTX130 allogeneic CRISPR-Cas9-engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Long-term follow-up and translational data from the phase 1 COBALT-RCC study

Abstract Background: The mainstay of therapy for clear cell renal cell carcinoma (ccRCC), the most prevalent subtype of kidney cancer, includes checkpoint inhibitors (CPIs) and tyrosine kinase inhibitors (TKIs). However, once patients progress on these drug classes, outcomes are poor. Here, we report durable response and stability observed in a Phase 1 dose-escalation study of CTX130™, a CD70-targeting allogeneic CAR T cell therapy in patients with ccRCC. Methods: In this phase I study, patients were recruited from sites in the United States, Europe and Australia. Key eligibility included advanced ccRCC with prior receipt of at least one CPI and TKI. After receipt of standard lymphodepletion with fludarabine and cyclophosphamide for 3 days (dosed at 30 mg/m2 and 500 mg/m2, respectively), patients received infusion of CTX130. Results: Among the 16 patients enrolled and treated in dose escalation, the median age was 63 (range, 53-77) and all were stage IV at the time of enrollment. Patients had received a median of 3 prior lines of therapy (range, 1-6). Doses ranging from 3 × 107 to 9 × 108 CAR T cells were administered, and no dose-limiting toxicities were encountered. Cytokine release syndrome (CRS) was observed in 8 patients (50%); all events were grade 1 or 2. Infections were observed in 4 patients (25%), all deemed to be unrelated to CTX130. No hemophagocytic lymphohistiocytosis, graft-versus host disease or treatment-related neurotoxicity was observed. As of Oct 9, 2023, 1 patient (6.3%) achieved a complete response (CR) (now extending over 36+ months) and 12 additional patients (75%) achieved stable disease (SD) (1 patient in excess of 18 months), reflecting a disease control rate (CR/partial response/SD) of 81.3%. Immunohistochemical staining of baseline and archival tissues show an initial median CD70 expression level of 100% (range, 1-100%), with no substantial antigenic loss at sequential biopsies performed at day 42. Using digital droplet PCR assays of the CAR construct, we assessed expansion. CTX130 was detected in 20 minutes after infusion, declined to a nadir 2-3 days later, followed by rapid expansion between days 7 and 15. In general, expansion increased at each dose level. Conclusions: Updated results from the COBALT-RCC study reinforce both the encouraging antitumor activity and exceptional safety profile of CTX130. The durable CR, now in excess of 3 years, reflects the first and longest seen with allogeneic CAR T cell therapy in refractory solid tumors. A study of CTX131™ (building on CTX130 with CRISPR edits to enhance potency and persistence) is ongoing. Citation Format: Sumanta Kumar Pal, Ben Tran, John B. Haanen, Michael Hurwitz, Adrian Sacher, Neeraj Agarwal, Nizar Tannir, Elizabeth Budde, Simon Harrison, Sebastian Klobuch, Sagar S. Patel, Mary-Lee Dequeant, Qiuling Ally He, Alissa Keegan, Henia Dar, Anna Ma, PK Morrow, Samer A. Srour. CTX130 allogeneic CRISPR-Cas9-engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Long-term follow-up and translational data from the phase 1 COBALT-RCC study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT002.

Abstract CT160: A phase I trial to evaluate allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells in subjects with advanced solid tumors or hematological malignancies (the ANGELICA Trial)

Abstract Background: Adoptive cellular therapy (ACT) has been transformative in the treatment of hematological malignancies. Limitations of ACTs include difficulty identifying suitable tumor antigens for solid tumors, the ability to target only one antigen per construct which commonly results in secondary resistance due to antigen escape, and largely autologous approaches which are challenging in heavily pre-treated patients with poor marrow function and those with rapidly progressive disease who may not receive their personalised cellular products in time. This is a phase I study evaluating a novel off-the-shelf allogenic mRNA-electroporated NKG2D ligand-targeting CAR-grafted γδ T cell therapy. NKG2DLs are a group of 8 types of stress-induced cancer antigens which are preferentially and widely expressed on tumor cells from diverse tissue origins but are not typically present on normal tissue. NKG2DL-targeting γδ T cells will be manufactured from peripheral blood mononuclear cells isolated from healthy donors enrolled on the donor protocol of the ANGELICA trial. ANGELICA is a phase I study evaluating the safety, tolerability and recommended phase 2 dose (RP2D) of NKG2DL-targeting CAR-grafted γδ T cells in patients with treatment refractory tumors. Methods: Patients will be enrolled in a 3+3 design. Dose escalation will be performed at 3 dose levels: 1x108, 3x108 and 1x109 per infusion (adjusted for body weight). Lymphodepletion with fludarabine 25mg/m2/day and cyclophosphamide 250mg/m2/day will given for 3 days and completed at least 2 days prior to the first cycle of treatment. Patients will receive 4 doses of weekly infusions for the first cycle, with up to 5 subsequent infusions every 2 months as maintenance. Patients will receive intravenous zoledronic acid 1mg prior to each cellular infusion and subcutaneous IL-2 1x106 IU/m2 within 2 hours of each cellular infusion as pre-clinical data demonstrated cancer cell sensitisation and prolonged γδ T cell survival with these adjuncts. Dose-limiting toxicities will be assessed over the first 8 weeks. Adverse events, response rates (RECIST v1.1), survival outcomes and immunomonitoring (immune cell phenotyping and serum cytokine analysis) will be assessed. The trial is currently enrolling healthy donors; enrolment of patients at the first dose level will begin in February 2024. NCT05302037 TABLE 1: NAND Dose Level and Schedule Dose Level Dose per infusion Infusion schedule Number of patients 1 Weight 65kg and above: 1x108.Weight less than 65kg: 1.5x106. Cycle 1: weekly x 4 infusions. Maintenance phase: 2-monthly x 5 infusions. 3-6 2 Weight 65kg and above: 3x108.Weight less than 65kg: 4.6x106. 3-6 3 Weight 65kg and above: 1x109.Weight less than 65kg: 1.5x107. 3-6 Citation Format: Joan Choo, Wee Kiat Tan, Lucas Luk, Jieming Zeng, Teck Guan Soh, Sou Yen Soon, Jedidah Lieow, Calista Wong, Mei Yan Pang, Sudipto Bari, Michelle Poon, Liang Piu Koh, Wee Joo Chng, Anand Jeyasekharan, Lip Kun Tan, Esther Chan, Raghav Sundar. A phase I trial to evaluate allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells in subjects with advanced solid tumors or hematological malignancies (the ANGELICA Trial) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT160.

Abstract CT099: NGM707 in combination with pembrolizumab in advanced or metastatic solid tumors: Preliminary results from dose escalation

Abstract BACKGROUND: NGM707-IO-101 (NCT04913337) is a Phase 1/2, dose escalation/expansion study evaluating NGM707, a humanized monoclonal antibody that blocks ILT2 and ILT4 receptors, as monotherapy or in combination with pembrolizumab. Here we report data from the combination part of the study. METHODS: Eligible patients (pts) with advanced/metastatic solid tumors were enrolled into escalating dose cohorts of 200-1800 mg NGM707 combined with 200 mg pembrolizumab, administered Q3W iv. Assessment of safety and tolerability and recommended expansion doses for NGM707 in combination with pembrolizumab were the primary objectives of the study. Secondary and exploratory objectives included assessment of pharmacokinetics/receptor occupancy (RO), immunogenicity, biomarkers, and preliminary antitumor activity per RECIST v1.1. RESULTS: As of 06 Nov 2023, 46 pts have been enrolled in the combination escalation at dose levels up to 1800 mg; 5 pts crossed over from monotherapy. Median age 58.5 yrs [28-81]; ECOG PS 0 (19.6%), 1 (80.4%). Pts had received a median of 3 prior therapies (range 1-6) and all pts had metastatic disease. Overall, 20/45 pts had prior exposure to anti-PD1/anti-PD-L1. Treatment-related adverse events (any grade/grade ≥3) occurred in 41.3%/4.4% of pts. The most common treatment-related adverse events were fatigue (17.4%), diarrhea (6.5%), myalgia (4.3%), arthralgia (4.3%), and nausea (4.3%). No dose-limiting toxicities were observed. A maximum tolerated dose was not reached, and the maximum administered dose was 1800 mg NGM707 in combination with 200 mg pembrolizumab. Peripheral immune cells showed dose-dependent RO, with doses ≥ 200 mg maintaining ILT2 and ILT4 RO for the entire dosing interval. PK of NGM707 was typical for monoclonal antibodies, with a half-life of 12.8 days. Gene expression changes associated with myeloid cell and T cell activation were observed in tumor biopsies post-treatment. Of 37 response-evaluable pts, best overall responses to date are PR (confirmed) in 4 pts, SD in 12 pts, representing a DCR of ~43%. Nine pts had reduced target lesion (TL) size with a maximum reduction of 100%. Out of the 4 patients who had PR, 3 patients were pre-treated with anti-PD1/anti-PD-L1. Two subjects with MSS CRC achieved confirmed PR, one of them with TL reduction that allowed subsequent surgical resection of all gross residual disease and confirmed pathological CR with no active tumor cells and ctDNA below detection. CONCLUSIONS: NGM707 in combination with pembrolizumab appears to be safe and well tolerated at all dose levels. In this advanced and metastatic solid tumor cohort, early efficacy signals have been observed. Preliminary evidence of myeloid cell reprogramming was observed in paired tumor biopsies. Trial enrollment for the expansion part of the study is ongoing and updated data will be presented in the future. Citation Format: Judy S. Wang, Manish R. Sharma, William J. Edenfield, Kartik Sehgal, Do-Youn Oh, Yixing Jiang, Joel Michalski, Jeeyun Lee, Hans Hammers, Li-Yuan Bai, Chih-Hung Hsu, Brenda Dampier, Kefei Zhou, Li Yan, Lisa K. Blum, Joanne Sloan-Lancaster, Daniel D. Kaplan, Dhiraj Abhyankar, Hsiao D. Lieu, Vladimir Hanes, Aung Naing. NGM707 in combination with pembrolizumab in advanced or metastatic solid tumors: Preliminary results from dose escalation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT099.

Abstract CT195: First-in-human phase 1 study of WEE1 inhibitor APR-1051 in patients with advanced solid tumors harboring cancer-associated gene alterations

Abstract Background: WEE1 tyrosine kinase plays a key role in cell cycle regulation and DNA damage responses, acting as a principal gatekeeper of the G1-S and G2-M cell cycle checkpoints. Thus, inhibition of WEE1 can result in high cyclin-dependent kinase 1 and 2 activities, leading to aberrant cell cycle progression. Increasing premature entry into mitosis and subsequent apoptosis via WEE1 inhibition is one potential approach to killing cancer cells effectively. APR-1051 is an orally bioavailable, highly potent, small molecule inhibitor of WEE1 that has demonstrated in vivo anti-proliferative activity in multiple cancer cell lines and high selectivity for WEE1 versus polo-like kinases 1, 2, and 3. Increased selectivity for WEE1 may reduce the myelosuppressive toxicity (e.g., limiting Grade 3 toxicities) reported with other WEE1 inhibitors. Methods: The primary aim of this multi-center, open-label Phase I study is to characterize the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD)/maximum administered dose (MAD) and recommended Phase 2 dose (RP2D) of APR-1051 in patients with advanced solid tumors harboring cancer-associated gene alterations. Secondary objectives include evaluating the pharmacokinetic (PK) properties of APR-1051, assessing the effect of food on its PK, and its preliminary efficacy per RECIST version 1.1. The exploratory objective is to assess the pharmacodynamic effects of APR-1051. For dose escalation, an accelerated titration followed by a BOIN design will be utilized to determine the MAD/MTD. Upon completion of the dose escalation, two suitable doses and schedules of single-agent APR-1051 will be determined for further investigation in dose selection optimization. Key inclusion criteria are age at least 18 years with advanced solid tumor and cancer-associated gene alterations (e.g., amplification/overexpression of CCNE1 or CCNE2, deleterious mutations in FBXW7 or PPP2R1A), ECOG PS 0 or 1, and adequate organ function. Key exclusion criteria are cancer therapy within 3 weeks or at least 5 half-lives, prior radiation therapy at the target lesion except if evidence of disease progression, unresolved therapy-related AEs, investigational agent within 5 half-lives or 30 days of study drug, prior WEE1 inhibitor, CNS metastases or unstable involvement, secondary malignancies that are active and/or require therapy, and concomitant moderate/strong inhibitors/inducers of CYP3A4/5, MDR1, or BCRP. Up to 79 patients will be enrolled at 3 to 5 sites in the United States. Citation Format: Timothy A. Yap, Crystal Miller, David Stenehjem, Eric J. Brown, Mike Carleton, Nadeem Q. Mirza. First-in-human phase 1 study of WEE1 inhibitor APR-1051 in patients with advanced solid tumors harboring cancer-associated gene alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT195.

Abstract CT007: Phase 1/2 trial of copanlisib in combination with nivolumab for microsatellite stable (MSS) colorectal cancer (CRC)

Abstract Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) is frequently mutated in CRC, leading to constitutive activation and enhanced cellular growth. PI3K also regulates immunity; inhibition of this pathway suppresses Tregs and myeloid derived suppressor cells resulting in enhanced anti-tumor immune responses. Murine experiments combining PD-1 and PI3K inhibition showed an increased CD8+ T cell:Treg ratio and improved survival compared to either alone. We launched a multicenter phase I/II investigation of copanlisib (PI3K inhibitor) and nivolumab (anti-PD-1) in 2 cohorts of patients with metastatic MSS CRC, Cohort 1: PIK3CA mutant (PI3KCAm) and Cohort 2: PIK3CA wild type (PIK3CAwt). From 2/2019 to 4/2022, 39 patients were enrolled: 6 in the phase 1 portion and 33 in phase 2 (22 PIK3CAm/17 PIK3CAwt). All patients had received at least 2 lines of prior therapy. Patient demographics and best treatment responses are in Table 1. There were no dose-limiting toxicities; toxicities were as expected and tolerable, most commonly hypertension in 16 (41%) patients and maculopapular rash in 4 (10%) patients. 3 patients in cohort 1 (14%) had partial responses (PR) and 3 had stable disease (SD): (range 1.7-4.7 mo.). One patient in Cohort 2 (6%) had a PR and 4 had SD: (range 3.8-7.4 mo.). Notably, all 4 responses have lasted more than 2 years. The trial incorporated robust translational correlates for mechanism interrogation with serial biopsies and blood draws. We will report circulating cytokine profiling, mass cytometry on PBMCs, and highly multiplexed immunofluorescence imaging (CyCIF) on paired pre- and on-treatment tissue specimens to i) dissect immune and PI3K pathway changes with treatment ii) correlate these to clinical responses and iii) determine baseline biomarkers of response and mechanism of effect. Overall copanlisib/nivolumab was well tolerated. The PIK3CAm CRC cohort met the primary endpoint for objective response rate but later than 6 months as responses were evolving. Table 1: Demographics and Best Treatment Responses of Patients Treated on NCT03711058: Study of Copanlisib and Nivolumab in MSS Colorectal Cancer Age Sex Race RAS-RAF status Best Response TMB Total (n=39) 58 (40-83) F: 53%(21), M: 47%(18) AA: 15%(6), AS: 8%(3), W: 77%(30) Altered: 67%(26), Wild type: 33%(13) PR: 10%(4), SD: 18%(7), PD: 72%(28) 5 (1-10) PIK3CA mutant (n=22) 57.5 (42-83) F: 73%(16), M: 27%(6) AA:23%(5), AS: 9%(2), W: 68%(15) Altered: 73%(16), Wild type: 27%(6) PR: 14%(3), SD: 14%(3), PD: 73%(16) 5 (1-10) Exon 9 mutation (n=13) 58 (45-83) F: 77%(10), M: 23%(3) AA: 15%(2), AS: 8%(1), W: 77%(10) Altered 85%(11), Wild type: 15%(2) PR: 8%(1), SD: 8%(1), PD: 85%(11) 7.9 (1-18) Exon 20 mutation (n=5) 62 (43-76) F: 80%(4), M: 20%(1) AA: 20%(1), W: 80%(4) Altered: 80%(4), Wild type: 20%(1) PR: 20%(1), SD: 20%(1), PD: 60%(3) 4 (3-8) Other (n=4) 46 (42-54) F: 50%(2), M: 50%(2) AS: 25%(1), AA: 50%(2), W: 25%(1) Altered: 75%(3), Wild type: 25%(1) PR: 25%(1), PD: 75%(3) 5.3 (3-7.6) PIK3CA wild type (n=17) 59 (40-81) F: 29%(5), M: 71%(12) AA: 6%(1), AS: 6%(1), W: 82%(15) Altered: 59%(10), Wild type: 41%(7) PR: 6%(1), SD: 24%(4), PD: 71%(12) 5.5 (1-9) AA: African American, AS: Asian, C: Caucasian, F: Female, M: Male, PD: Progressive disease, PR: Partial Response, SD: Stable disease Citation Format: Eric S. Christenson, Jeremiah A. Wala, Rose Parkinson, Natalie B. Collins, Christopher Jakubowski, Jea-Ren Lin, Hao Wang, Won Jin Ho, Sabrina Chan, Rachel Klein, Yvette Cetasaan, Emma Johnson, Maureen Berg, Jeffrey Meyerhardt, Benjamin Schlechter, Harshabad Singh, Peter K. Sorger, Marios Giannakis, Nilofer Azad. Phase 1/2 trial of copanlisib in combination with nivolumab for microsatellite stable (MSS) colorectal cancer (CRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT007.

Abstract CT147: Phase I clinical study of Bruton’s tyrosine kinase inhibitor (BTKi) HBW-3220 capsules in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL)

Abstract Purpose: This clinical study is to evaluate HBW-3220, a novel reversible BTK inhibitor (BTKi) with an improved in vitro profile than the existing non-covalent drugs pirtobrutinib (LOXO-305, approved) and MK-1026 (Phase III). HBW-3220 shows superior inhibition against BTK wild-type and several common mutants, such as C481S, C481R, T474I, T316A, and L528W (the one predominantly enriched in patients resistant to the newer-generation BTKis), and hematopoietic cell kinase (HCK), a key contributor to the development of ibrutinib resistance associated with kinase-defective BTK. Methods: This phase I clinical study was conducted in R/R B-NHL patients who had received two or more prior lines of treatments. The dose escalation study adopts accelerated titration and a "3+3" design, with a daily single dose of 15, 30, 60, 90, 120, or 150 mg. During the dose escalation phase, the sponsor and investigators determined whether to expand the cohort of the previous dose based on the existing data. Adverse events (AEs) were assigned according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response assessment was based on the iwCLL 2018 guidelines, the IWWM-7 consensus, or the Lugano 2014 guidelines, according to the respective disease type. Results: 28 patients have been enrolled so far, and the dose escalation study has been completed. No dose-limiting toxicity (DLT) occurred in any patient, implicating good tolerability. Adverse events (AEs), similar to other BTKis, were mostly Grade 1 or 2, including fever (38%), diarrhea (35%), headache (19%), anemia (42%), infectious pneumonia (23%), decreased neutrophils (42%), decreased platelet count (27%), increased alanine aminotransferase (23%), etc. Drug-related Grade 3 AEs included neutrophil count decreased (n=3, 11%), increased lymphocyte count (n=2, 7%), and infectious pneumonia (n=2, 7%). 21 patients underwent at least 1 response assessment (4 chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); 4 marginal zone lymphoma (MZL); 5 mantle cell lymphoma (MCL); 3 diffuse large B-cell lymphoma (DLBCL); 5 other B-NHL), and the results are 1 complete response (CR), 6 partial response (PR), and 1 partial response with lymphocytosis (PR-L). The overall response rate (ORR) in CLL/SLL (all with prior irreversible BTKi treatment, and 2 of them with additional BCL2 inhibitor treatment), MZL, MCL, and DLBCL patients were 75% (3/4, including 1 PR-L), 50% (2/4), 40% (2/5) and 33% (1/3), respectively. Among the ORR (including CR, PR, and PR-L), 88% (7/8) were in the 90 mg and above dose group, regardless of previous BTKi treatment history or mutation status of p53 and BTK C481S. In the 90 mg and above dose group, the ORR is 47%. After oral administration, the drug exposures showed dose-dependent increases. The time to maximum plasma concentration (Tmax) was 2 hours, and the elimination half-life (T1/2) was 19 hours. Conclusions: The current data show that HBW-3220 is well tolerated, showing no DLT occurred at daily doses up to 150 mg, and has good efficacy in patients with CLL/SLL, MZL, and MCL. Citation Format: Ning Lee, Yingfu Li, Yong Mao, Guanfeng Liu, Jiang Li, Qingchun Liu. Phase I clinical study of Bruton’s tyrosine kinase inhibitor (BTKi) HBW-3220 capsules in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT147.

Abstract CT118: Phase I dose escalation of ASKC202, a novel cMET tyrosine kinase inhibitor, in patients with advanced solid tumors

Abstract Background ASKC202 is an oral and highly selective small molecule inhibitor which inhibits mesenchymal-epithelial transition. We report preliminary safety and efficacy data from an ongoing Phase I, FIH, dose-escalation study of ASKC202 in patients (pts) with advanced solid tumors (NCT05306132). Methods A two-part study was initiated to evaluate MTD, safety and tolerability, pharmacokinetics and preliminary antitumor activity of ASKC202, including dose escalation study (Part A) and dose expansion study (Part B). Responses were assessed per RECIST 1.1 every 2 cycles (6 weeks). AEs were graded using CTCAE v5.0.In Part A, dose escalation followed the accelerated titration combined with the "3+3" design. Patients with heavily pre-treated solid tumors received ASKC202 orally at doses of 50, 150, 300, 450 and 600 mg/day once daily. The treatment continued until disease progression, unacceptable toxicity or treatment termination. If the subject in the 50mg dose group developed DLT, the dose group was switched to a "3+3" design. Results As of November 30, 2023, 16 patients who are refractory or don’t respond to standard therapy were available received ASKC202 (50mg: N=1; 150mg: N=3; 300mg: N=6; 450mg: N=3; 600mg: N=3). 15/16 pts had pathological confirmation of non-small-cell lung cancer (except for 1 case of PSC). 8/16 pts had brain metastasis. 10/16 pts had cMET dysregulation including MET amplification (N=9; gene copy number 1.3-8.3) and MET missense mutation (N=1; p.S186L) with no patient having Exon 14 skipping mutation.ASKC202 was well-tolerated in all patients. No dose-limiting toxicity was observed in all dose levels (50 to 600 mg). The common TRAEs occurring in more than 20% of patients included: anemia (5/16), blood glucose elevation (5/16), ALT elevation (4/16), AST elevation (4/16) and peripheral edema (4/16). Grade 3 TRAEs were only observed in one patient (300mg QD), including anemia and hypokalemia. Among 14pts who had at least one post-baseline anti-tumor assessment, 5 pts achieved a confirmed partial response. The confirmed ORR is 35.7%. The median best percentage change in target lesion size from baseline (depth of response) was 51.8% and 3pts had duration of tumor response ≥ 6 months. ORR and DCR for patients with cMET alteration (N=8) was 62.5% (5/8) and 75.0% (6/8) respectively. One subject (150mg QD) with MET missense mutation (p.S186L) had a 67% tumor reduction in intracranial lesion from baseline. Exposure of ASKC202 increased dose-proportionally at dose range 50mg to 300mg, but less than dose-proportionally increased at 300mg to 600mg. Conclusions ASKC202 monotherapy was well-tolerated with manageable safety profile and showed anti-tumor signal and the central nervous system efficacy. Citation Format: Tingting Song, Caicun Zhou, Wei Li, Xingya Li, Lin Wu, Shan Zeng, Liyun Miao, Baogang Liu, Xuyu Wei, Jing Chen, Luwei Han. Phase I dose escalation of ASKC202, a novel cMET tyrosine kinase inhibitor, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT118.

Abstract CT064: Impact of food and high gastric pH on the bioavailability of the WEE1 inhibitor Debio 0123 assessed in a phase 1 dose escalation study

Abstract Debio 0123 (D0123), an oral, brain-penetrant, highly selective WEE1 inhibitor, is currently in clinical development, both in combination and as monotherapy, for the treatment of patients with solid tumors. Food and gastric acid-reducing agents e.g. proton pump inhibitors (PPIs) may modify the solubility, bioavailability, safety and efficacy of oral cancer drugs. Polymedication in cancer patients is common and food restrictions can impact patient compliance and wellbeing. In order to adequately inform drug dosing in clinical trials, effects of food and high gastric pH on D0123 bioavailability were studied over three cycles in patients treated in the dose escalation of a Phase 1 study of D0123 in combination with Carboplatin (CTID NCT03968653).D0123 was given on Days 1-3 and 8-10 of each 21-day cycle in combination with carboplatin on Day 1. Current standard administration of D0123 is in fasted conditions and PPIs are prohibited. Dose-limiting toxicities were evaluated in cycle 1. The effect of food and high-gastric pH were assessed in cycles 2 and 3, respectively. In cycle 2 on Day 10, patients were receiving a high-fat meal and in cycle 3, the PPI lanzoprazole 30 mg BID was administered from Day 7 to 11. PK parameters (area under the curve (AUC), maximum concentration (Cmax)) were determined post-Day 10 dose and compared between cycle 1 (fasted) and cycle 2 (fed) or 3 (high gastric pH). Preliminary data from 3 cohorts, 3 dose levels (n=10) resulted in about 5 pairwise comparisons for food and for high gastric pH effects. Absence of D0123 accumulation between cycles was confirmed, allowing for inter-cycle comparison. Oral bioavailability of D0123 appears pH-dependent, suggesting that co-medication with PPIs should be avoided. In contrast, food intake has a limited impact on drug absorption, at all doses tested. Furthermore, D0123 administration with food may increase treatment convenience and tolerability, leading to its implementation in other D0123 trials. TABLE 1. NAND Mean change [ min ; max ] Effect of food (cycle 2 versus cycle 1) Effect of high gastric pH (cycle 3 versus cycle 1) AUC24 -3% [ -17% ; +8% ] -31% [ -39%; -23% ] Cmax -10% [ -26% ; 0% ] -33% [ -41% ; -20% ] Citation Format: Anne Bellon, Omar Saavedra, Ingrid M. Desar, Mathilde Jalving, Jourik A. Gietema, Carla van Herpen, Stefan van Ravensteijn, Esteban Rodrigo Imedio, Sylvia van Haren, Melanie Wirth, Sandrine Micallef, Vito Dozio, Rikke Frederiksen Franzen, Marie-Claude Roubaudi-Fraschini, Valerie Nicolas-Metral, Hans Gelderblom. Impact of food and high gastric pH on the bioavailability of the WEE1 inhibitor Debio 0123 assessed in a phase 1 dose escalation study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT064.

Abstract CT201: Phase 2 clinical trial of OKN-007 in recurrent malignant glioma

Abstract Background: OKN-007 is a novel nitrone anti-cancer agent. OKN-007 plus Temozolomide (TMZ) increased survival in glioma-bearing mice compared to TMZ alone. Furthermore, OKN-007 increased TMZ sensitivity in both TMZ-sensitive and TMZ-resistant cell lines. Following a phase I study in recurrent glioblastoma (rGBM), we initiated a phase 2 clinical trial (NCT04388475) of OKN-007 combined with TMZ to examine the efficacy, safety, and pharmacokinetic properties of OKN-007 combined with TMZ. Here, we report the safety and efficacy findings of this ongoing trial. Methods: This is a multi-center, open label phase 2 clinical trial in first or second rGBM WHO Grade (Gr) IV. Adult patients with rGBM previously treated with standard radiation and chemotherapy (Stupp regimen) were eligible. Any second-line therapy was acceptable, excluding bevacizumab. Patients were treated with OKN-007, administered intravenously, at 60 mg/kg, three times weekly for 12 weeks, then twice weekly for 12 weeks, then once weekly until progression. TMZ was administered orally, at a dose of 150 mg/m2 (Cycle 1) or 200 mg/m2 (subsequent cycles). An initial 3-patient safety lead-In cohort established the safety of the OKN-007 and TMZ combination in this patient population. Kaplan-Meier analysis was used to determine progression-free (PFS) and overall survival (OS). Additionally, a comparative analysis of PFS and OS for a matched external control rGBM population treated with lomustine in other formal randomized clinical trials was performed. Results: 57 patients were enrolled at study completion. Of 57 patients enrolled, there were no adverse events (AEs) deemed as a dose-limiting toxicity in the safety Lead-In cohort with 3 patients. Median age was 56 years (range, 29-82), and 41 patients were treated with one line of prior anti-cancer therapy and 15 were treated with two prior lines. Eighteen patients experienced 46 SAEs and of these 9 (Gr3 nausea, Gr2 vomiting, Gr3 fatigue, Gr2 infusion related reaction, Gr3 acute liver injury, Gr3 generalized weakening upper and lower extremities, Gr3 bilirubin increase, Gr3 AST and ALT increase) were deemed to be possibly related to administration of OKN-007. For 56 patients receiving the combination of OKN-007 and TMZ, median PFS was 2.2 (95% CI, 1.6-3.6) months vs. 1.8 (95% CI, 1.7-1.9) months in control patients. Median OS was 9.7 (95% CI 7.6-12.5) months vs. 7.2 (95% CI, 6.8-7.8) months (Cox hazard ratio (HR) = 0.68, p = 0.034). 6-month PFS rate was 23.6% (95% CI, 13.5-35.4) vs. 13.0% (95% CI, 10.0-16.4) and 12-month OS rate was 38.1% (95% CI, 25.1-50.9) vs. 26.3% (95% CI, 22.0-30.8), respectively. Conclusions: Our data indicate that the combination therapy of OKN-007 and TMZ appears safe and, compared to standard lomustine therapy, may prolong OS in rGBM. Citation Format: James Battiste, Glenn Lesser, Santosh Kesari, Varun Monga, Tobias Walbert, Kaylyn Sinicrope, Burt Nabors, Jason Schroeder, Eric Wong, Barry D. Anderson, Hyun Sook Kim, Shinwook Kang. Phase 2 clinical trial of OKN-007 in recurrent malignant glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT201.

Abstract CT077: An open-label phase 1 study to investigate SGN-CEACAM5C in adults with advanced solid tumors (SGNCEA5C-001, Trial in Progress)

Abstract Background Patients (pts) with recurrent or metastatic solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), colorectal cancer (CRC), gastric adenocarcinoma (GC), and pancreatic ductal adenocarcinoma (PDAC), have limited treatment options with short PFS and OS despite recent advances (Bordry 2021; Chakrabarti 2022; Merle 2022). Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is highly expressed across multiple solid tumors, such as CRC, GC, PDAC, and NSCLC. Restricted normal tissue expression and efficient lysosomal trafficking of CEACAM5 highlight its potential as an anticancer target. SGN-CEACAM5C is a novel investigational antibody-drug conjugate (ADC) directed to CEACAM5 composed of the humanized immunoglobulin G (IgG1) anti-CEACAM5 monoclonal antibody tusamitamab chemically conjugated to 8 molecules of the topoisomerase 1 inhibitor 7-aminomethyl-10,11-methylenedioxycamptothecin (AMDCPT). SGN-CEACAM5C selectively binds to CEACAM5 present on the cell surface and is internalized via the endo-lysosomal pathway, with subsequent release of the payload through enzymatic cleavage. Release of the cytotoxic payload induces DNA damage, cell cycle arrest in S phase, and apoptosis in tumor cells. In vitro bystander activity was observed against tumor cells without CEACAM5 surface expression. SGN-CEACAM5C is highly active in multiple patient-derived xenograft models, including CRC, GC, and NSCLC, across various levels of CEACAM5 expression (Baudat 2023; Baudat 2024). These preclinical findings justify evaluation of SGN-CEACAM5C in a clinical trial setting. Methods SGNCEA5C-001 (NCT06131840) is a phase 1, open-label, multicenter study designed to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of SGN-CEACAM5C in adults with select advanced solid tumors. This study consists of dose escalation (Part A), dose and schedule optimization (Part B), and dose expansion (Part C). Eligible pts are adults ≥18 years of age with confirmed metastatic or unresectable solid tumor malignancy, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, an ECOG PS of 0-1, and 1 of the following tumor types: CRC, GC/gastroesophageal junction adenocarcinoma (GEJ), PDAC, NSCLC (squamous/non-squamous), or SCLC. Primary endpoints include incidence of AEs, laboratory abnormalities, dose modifications due to AEs, dose-limiting toxicities, and cumulative safety. Secondary endpoints include estimates of PK parameters, incidence of antidrug antibodies, objective response rate and best response per RECIST v1.1 by investigator, duration of response, PFS, and OS. Safety and antitumor activity endpoints will be summarized using descriptive statistics. Recruitment is ongoing for Part A in North America. Citation Format: Funda Meric-Bernstam, Cesar A. Perez, Nehal Lakhani, Meredith Pelster, Justin Call, Suzanne McGoldrick, Tianhua Wang, Brigitte Demers, Amita Patnaik. An open-label phase 1 study to investigate SGN-CEACAM5C in adults with advanced solid tumors (SGNCEA5C-001, Trial in Progress) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT077.

Abstract CT259: Results from monotherapy dose escalation of MDNA11, a long-acting IL-2 superkine, in a phase 1/2 trial show evidence of single-agent activity in advanced solid tumors

Abstract Background: MDNA11 is an albumin-fused ‘beta-enhanced not-alpha’ IL-2 agonist engineered to preferentially expand and activate CD8+ T and NK cells with minimal impact on Tregs. The ABILITY-1 (A Beta-only IL-2 ImmunoTherapY) is a global Phase 1/2 study evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of MDNA11, both as single agent and in combination with a PD-1 inhibitor, in pre-treated patients with advanced solid tumors. Method: The ABILITY-1 study (NCT05086692) comprises monotherapy dose escalation/evaluation with a modified 3+3 design (enrollment complete); monotherapy dose expansion (enrolling); combination with pembrolizumab dose escalation (enrolling) followed by combination expansion. Thirty participants were enrolled in the monotherapy cohorts (3, 10, 30, 60, 90, and 120 μg/kg, IV, Q2W): 23 in dose escalation and 7 in dose evaluation. To enhance tolerability, step-up dosing with 2 or 3 priming doses was implemented starting at 60 μg/kg. Primary endpoints were incidence and severity of adverse events (AEs) and secondary endpoints included PK, PD, and tumor response (RECIST 1.1 and iRECIST). Results: As of December 22, 2023, 30 patients were enrolled in dose-escalation/evaluation, comprising 16 melanoma, 3 NSCLC, 3 PDAC, 2 RCC, 2 sarcoma, 2 ovarian cancer, 1 tonsillar squamous cell carcinoma and 1 gastro-esophageal adenocarcinoma. No dose-limiting toxicities (DLTs) were observed. Most common treatment related AEs were infusion-related reactions (53.3%), primarily grade 1-2, encompassing pyrexia (43.3%), nausea (33.3%), chills (33.3%), hypotension (30%), and fatigue (26.6%) that resolved within 48-72 hours. PK analysis showed sustained dose-dependent increase in serum concentration of MDNA11 with repeat doses. PD evaluation showed robust and durable dose-dependent increase in lymphocyte counts without eosinophilia. Immune effector cells, particularly CD8+ T cells, showed durable expansion with evidence of activation markers (CD25, ICOS and OX40) peaking at the 90 μg/kg dose. Single-agent anti-tumor activity was evident among 26 evaluable patients with confirmed partial responses (PRs) in a PDAC (MSI-H) patient (60 μg/kg cohort) and a melanoma patient (90 μg/kg cohort) as well as 8 (30.7%) stable disease (SD) including 3 melanoma patients with durable SD (>6 months, >8 months, >1.5 years). Based on the combined safety, PK, PD and preliminary anti-tumor activity, a recommended dose for expansion (RDE) of 90 μg/kg (preceded by priming doses of 30 and 60 μg/kg; Q2W) was selected for the ongoing monotherapy dose expansion of the ABILITY-1 study. Conclusions: MDNA11 was well-tolerated with no DLTs observed at all dose levels up to 120 μg/kg. With study currently ongoing, single agent clinical activity was evident with an ORR of 7.7% and Clinical Benefit Rate (CBR) of 19.2% (2 PRs + 3 SDs > 6 months) in dose escalation to date. Monotherapy dose expansion at 90 μg/kg and combination dose escalation with pembrolizumab are enrolling. Citation Format: Victoria G. Atkinson, Jesus F. Antras, Philippe Bedard, Warren Brenner, Jacqueline Brown, Charlotte R. Lemech, Peter Lloyd, Kim Margolin, Matthen Mathew, John J. Park, Sajeve Thomas, Przemyslaw Twardowski, Humphrey Gardner, Amy Prawira, Melissa Coello, Walead Ebrahimimizadeh, Minh D. To, Rosemina Merchant, Sudhir Madduri Karanam, Arash Yavari, Lillian L. Siu, Hussein A. Tawbi, Paolo A. Ascierto. Results from monotherapy dose escalation of MDNA11, a long-acting IL-2 superkine, in a phase 1/2 trial show evidence of single-agent activity in advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT259.

Abstract CT186: A first-in-human phase 1 dose-escalation and expansion study of intratumoral oncolytic reovirus (RC402) as a monotherapy or in combination with pembrolizumab in advanced solid tumors

Abstract Background: RC402 is an oncolytic reovirus that selectively infects and destroys cancer cells. Preclinical studies have shown that RC402 remodels the tumor immune microenvironments and elicits potent anti-tumor immunity, thereby enhancing immune checkpoint inhibitors. Methods: This Phase I clinical trial (ACTRN12620000777998) was designed to evaluate the safety profiles and antitumor efficacy of intratumoral (IT) RC402 in patients with advanced solid tumors refractory to standard therapy and with accessible tumor lesions for IT injection of RC402. For the dose-escalation part (Phase 1a), the RC402 monotherapy dose was evaluated at 3 dose levels in Part A and the RC402 combination therapy dose with pembrolizumab was evaluated at 2 dose levels in part B using an accelerated titration method followed by a standard 3+3 dose escalation. In the dose-expansion part (Phase 1b), patients were treated with IT RC402 in combination with pembrolizumab at the recommended dose selected from the dose escalation part. RC402 was IT injected on day 1 of each treatment cycle. Fixed-dose pembrolizumab (200mg Q3W) was intravenously administered on day 8 of each treatment cycle for Phase 1a Part B and Phase 1b. Viral shedding was assessed serially in serum, urine, sputum, and stool samples, and neutralizing antibodies to Reovirus Type 3 Dearing were analyzed in serum samples. Results: Nine patients (2 gastric cancer and 1 cutaneous squamous cell carcinoma [cSCC] in Phase 1a Part A, 1 cSCC and 1 colorectal cancer [CRC] in Phase 1a Part B, and 1 cSCC and 3 CRC in Phase 1b) were enrolled and treated with at least two doses of RC402. IT administration of RC402 was generally well tolerated with no dose-limiting toxicities at all dose levels (1.6 × 108, 1.4 × 109, and 1.4 ×1010 PFU) as a monotherapy or in combination with pembrolizumab. The maximum tolerated dose was not reached. There were no treatment-emergent adverse events (TEAEs) leading to treatment discontinuation and no RC402-related serious TEAEs. The most common AEs were chills, fatigue, injection site reactions (erythema and pain) and nausea. Response evaluation showed two complete responses (one patients with cSCC in Phase 1a Part A and another patient with cSCC in the dose expansion part) lasting longer than 90 weeks and 36 weeks, respectively. No viral shedding was detected in any serum, urine, sputum, and stool samples on days 1, 2, and 15 of cycle 1, on day 2 of subsequent cycles and at the end of treatment. All patients showed an initial increase in antireoviral antibody titers on day 1 of cycle 2, followed by a decrease in subsequent cycles. Conclusion: This first-in-human study demonstrated IT RC402 is well tolerated and has a manageable safety profile with preliminary clinical activity as a monotherapy and in combination with pembrolizumab. These results warrant further clinical development of RC402. Citation Format: Mark Voskoboynik, Jia Liu, Ki-Hoon Song, Dong-Guk Park, Min-Hee Ryu, Hong Jae Chon, Chan Kim. A first-in-human phase 1 dose-escalation and expansion study of intratumoral oncolytic reovirus (RC402) as a monotherapy or in combination with pembrolizumab in advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT186.