Abstract CT279: A phase 2 multicohort study to evaluate lorigerlimab (PD-1 x CTLA-4) in participants with advanced solid tumors

Apatinib combined with pegylated liposomal doxorubicin (PLD) versus PLD for platinum-resistant recurrent ovarian cancer (APPROVE): a multicenter, randomized, controlled, open-label, phase II trial

Purpose: Aurora kinases are associated with high proliferation, poor prognosis, and therapeutic resistance in several human tumor types. AMG 900 is an investigational, oral, highly potent, selective, pan-aurora kinase inhibitor. We evaluated the safety, tolerability, pharmacokinetics, and clinical activity of AMG 900 in pts with advanced solid tumors (NCT00858377). Methods: In the dose escalation phase, eligible pts were ? 18 years old, with advanced solid tumors that were refractory to standard treatment, measurable disease per RECIST, ECOG ? 2, and life expectancy > 3 months. In the dose expansion phase, eligible pts had taxane- and platinum-resistant epithelial ovarian cancer (OC), taxane-resistant triple-negative breast cancer (TNBC), or castration-resistant and taxane- or cisplatin-etoposide-resistant stage IV prostate cancer (CRPC). AMG 900 was administered 4 days on/10 days off at doses of 1 to 50 mg/day (dose escalation), and at the maximum tolerated dose of 40 mg/day with G-CSF support (dose-expansion). The primary objective was safety. Tumor response was determined per RECIST for all pts and additionally by GCIG CA-125 for pts with OC. Results: Treatment-related AEs were reported by 98 of 105 pts (93.3%). Myelotoxicities were the most common grade ? 3 treatment-related AEs. In the dose escalation (N = 50), 1 pt with OC (30-mg cohort) had a partial response (PR) by RECIST and GCIG. In the dose expansion (N = 55), 3 of 29 pts (10.3%) with OC had a PR by RECIST, and 7 of 29 pts (24.1%) had a PR by GCIG; 72.4% of pts with OC had stable disease (SD), and the disease control rate (PR + SD) was 82.8%. Median (95% CI) duration of response in pts with OC per RECIST was 24.1 (16.1, 34.1) weeks, and median (80% CI) PFS was 31.1 (23.6, 34.1) weeks. See table for additional results. Conclusions: AMG 900 had manageable toxicity with G-CSF support and promising single-agent activity in pts with heavily pretreated taxane- and platinum-resistant OC. Patient demographics, prior therapy, AEs, and best tumor responseDose escalation - advanced solid tumors (N = 50)OC (N = 29)TNBC (N = 14)CRPC (N = 12)Overall (N = 105)Male, n (%)21 (42.0)0 (0.0)0 (0.0)12 (100.0)33 (31.4)Female, n (%)29 (58.0)29 (100.0)14 (100.0)0 (0.0)72 (68.6)White or Caucasian, n (%)35 (70.0)23 (79.3)12 (85.7)11 (91.7)81 (77.1)Age, mean (SD), years56.5 (11.6)61.1 (11.4)54.6 (11.4)67.7 (8.0)58.8 (11.7)Prior lines of anti-cancer therapy, mean (SD)4.9 (3.2)5.3 (4.3)5.8 (3.0)4.5 (2.6)5.1 (3.4)Treatment-related AEs by preferred term (any grade), n (%)Fatigue21 (42.0)15 (51.7)6 (42.9)6 (50.0)48 (45.7)Neutropenia24 (48.0)14 (48.3)4 (28.6)4 (33.3)46 (43.8)Anemia15 (30.0)16 (55.2)6 (42.9)3 (25.0)40 (38.1)Nausea18 (36.0)10 (34.5)5 (35.7)5 (41.7)38 (36.2)Thrombocytopenia15 (30.0)11 (37.9)1 (7.1)2 (16.7)29 (27.6)Diarrhea14 (28.0)10 (34.5)1 (7.1)2 (16.7)27 (25.7)Alopecia13 (26.0)11 (37.9)1 (7.1)1 (8.3)26 (24.8)Decreased appetite11 (22.0)7 (24.1)2 (14.3)4 (33.3)24 (22.9)Vomiting9 (18.0)7 (24.1)5 (35.7)3 (25.0)24 (22.9)Leukopenia19 (38.0)3 (10.3)0 (0.0)1 (8.3)23 (21.9)Best tumor response - RECIST 1.1 criteria (central read), n (%)Complete response0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)Partial response1 (2.0)3 (10.3)0 (0.0)0 (0.0)4 (3.8)Stable disease29 (58.0)21 (72.4)7 (50.0)9 (75.0)66 (62.9)Progressive disease12 (24.0)3 (10.3)4 (28.6)1 (8.3)20 (19.0)Unable to evaluate8 (16.0)2 (6.9)3 (21.4)2 (16.7)15 (14.3) Citation Format: Montasser Shaheen, Ben Markman, Michael Carducci, Sara Hurvitz, Daruka Mahadevan, Dusan Kotasek, Oscar Goodman, Erick Gamelin, Vincent Chow, Gloria Juan, Erik Rasmussen, Gregory R. Friberg, Florian D. Vogl, Jayesh Desai. Phase 1, open-label, first-in-human study of AMG 900, an orally administered pan-aurora kinase inhibitor, in adult patients (pts) with advanced solid tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT045.

Background: Combining a PD-1 inhibitor and an agent with immune modulatory and antitumor properties may enhance antitumor activity of either agent. Sitravatinib, a spectrum-selective TKI targeting TAM receptors (Tyro3/Axl/MerTK) and VEGFR2, reduces the number of myeloid-derived suppressor cells and regulatory T cells while increasing the ratio of M1/M2-polarized macrophages, which may overcome an immunosuppressive tumor microenvironment and augment antitumor immune responses. Tislelizumab, an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages and abrogate antibody-dependent phagocytosis, has shown single-agent clinical activity in patients (pts) with advanced solid tumors. This open-label, multicohort, phase 1b study assessed safety/tolerability and preliminary antitumor activity of sitravatinib + tislelizumab in advanced solid tumors (BGB-900-103; NCT03666143). We report results from the PROC cohort. Methods: Anti-PD-(L)1 antibody-naïve pts with histologically confirmed, advanced PROC (disease progression <6 mo after last platinum treatment) were enrolled. While platinum-resistant pts were included, pts with platinum-refractory disease were excluded. Patients received sitravatinib 120 mg PO QD and tislelizumab 200 mg IV Q3W. Primary endpoint was safety/tolerability of sitravatinib + tislelizumab. Key secondary endpoints were investigator-assessed objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) per RECIST v1.1; overall survival (OS) was also assessed. PD-L1 IHC assay (Ventana SP263) and assessment of plasma VEGF/serum CXCL10 were retrospective. Results: As of Oct 13, 2020, 60 PROC pts were enrolled; 13 (22%) remained on treatment. Median age was 64 yrs (range 26-80); pts received a median of 4 (range 1-11) prior regimens. Median follow-up was 6.0 mo (range 0.2-23.4). Treatment-emergent adverse events (TEAEs) of any grade/grade ≥3 occurred in 97%/68% of pts; TEAEs led to sitravatinib dose reduction in 50% of pts. Nausea (33%), hypertension (18%), and abdominal pain (12%) were the most commonly reported grade ≥3 TEAEs. The 2 fatal AEs (malignant GI obstruction, dyspnea) were deemed unrelated to treatment. Confirmed ORR was 26.4% (95% CI, 15.3-40.3), with 14 pts achieving partial response; DCR was 77.4% (95% CI, 63.8-87.7). Median duration of response was 4.7 mo (95% CI, 2.8-not estimable). There was no clear association between PD-L1 expression and clinical response; plasma VEGF and serum CXCL10 increased after treatment (P<0.0001 for both). Median PFS was 4.1 mo (95% CI, 4.0-5.1); preliminary median OS was 12.9 mo (95% CI, 6.3-17.2). Conclusions: Sitravatinib + tislelizumab was tolerable and showed preliminary antitumor activity in pts with advanced PROC. Further investigation of sitravatinib + tislelizumab in PROC is warranted. Citation Format: Jeffrey Goh, Jermaine Coward, Bo Gao, Ines P. da Silva, Mark Voskoboynik, Daphne Day, Amy L. Body, Hui K. Gan, Cheng Chen, Xiao Xiang, Cong Fei, Liu Yang, Michael Millward. Safety/tolerability and preliminary antitumor activity of sitravatinib plus tislelizumab in patients with advanced platinum-resistant ovarian cancer (PROC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT013.

5533 Background: Non-platinum chemotherapy is widely used in platinum-resistant recurrent ovarian cancer treatment but with limited efficacy. Combing chemotherapy with angiogenic inhibitors is a new therapeutic choice. Anlotinib is a novel tyrosine kinase inhibitor targeting multiple receptors involved in tumor proliferation, vasculature, and tumor microenvironment. The study aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed in platinum-resistant ovarian cancer. Methods: Patients who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-resistant or platinum-refractory epithelial ovarian cancer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14; 21 days per cycle) orally plus pemetrexed intravenously (0.5 g/m2 on day 1; 21 days per cycle). Subsequent maintenance treatment was anlotinib monotherapy (12 mg QD from day 1 to 14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Jan 2021, 27 patients were enrolled. The median number of chemotherapy was 4 (range, 2-10) and 51.9% (14/27) of patients had ever received antiangiogenic therapy. The ORR was 36.4% (partial response (PR) in 8 patients; 95% CI, 17.2-59.3). The DCR was 100.0% (PR in 8 patients and stable disease (SD) in 14 patients; 95% CI, 73.5-100). The median time of the first response was 1.6 months (range, 1.3-4.4). The median PFS was 9.3 months (95% CI, NE-NE). Furthermore, the ORR of patients with and without prior antiangiogenic therapy was 16.7% (95%CI, 2.1-48.4) and 60.0% (95%CI, 26.2-87.8) respectively (P = 0.074). Any grades of adverse events (AEs) were observed in 92.6% (25/27) of patients, containing allergic eruption (33.3%), hand-foot syndrome (29.6%), hypertension (25.9%), and fatigue (25.9%). The grade 3-4 adverse events were only observed in 5 patients, including 1 with grade 3 proteinuria, 1 with grade 3 ascites, 1 with grade 3 fatigue, 1 with grade 3 edema limbs and 1 with grade 4 anemia. Conclusions: The treatment of anlotinib plus pemetrexed showed a promising antitumor activity with tolerable toxicity for patients in platinum-resistant and refractory ovarian cancer. Clinical trial information: ChiCTR2000029654.

TPS5609 Background: ARTISTRY-7 will evaluate the novel engineered cytokine nemvaleukin alfa (nemvaleukin, ALKS 4230) in pts with gynecologic cancers. Epithelial ovarian cancer (OC) is the 7th most common cause of cancer mortality in women. OC is an area of high unmet need, as many pts become resistant or refractory to frontline platinum-based chemotherapy. Nemvaleukin was designed to selectively bind to the intermediate-affinity interleukin-2 (IL-2) receptor, preferentially activating and expanding antitumor CD8+ T and NK cells with minimal expansion of Tregs. This selectivity may provide enhanced tumor killing and improved safety/tolerability compared with high-dose IL-2. In clinical studies, nemvaleukin, as monotherapy and in combination with pembrolizumab, has shown evidence of clinical benefit in multiple tumor types, including OC. In ARTISTRY-1, 4 responses were observed in pts with OC, including 2 complete responses, 1 in a pt with platinum-resistant OC and 5 prior lines of therapy, and 2 partial responses. Methods: ARTISTRY-7 is a phase 3, multicenter, open-label randomized study of nemvaleukin and/or pembrolizumab vs chemotherapy. Eligible pts are women (≥18 y) with histologically confirmed epithelial OC (high-grade serous, endometrioid, clear cell), fallopian tube cancer, or primary peritoneal cancer. Pts must have received ≥1 prior line of systemic therapy in the platinum-sensitive setting, ≤5 prior lines in the platinum-resistant setting, and prior bevacizumab, with radiographic progression on most recent therapy. Primary platinum-refractory disease (progression on first-line platinum therapy) or primary platinum resistance (progression < 3 months after completion of first-line platinum therapy) is exclusionary. Pts must have ECOG performance status of 0 or 1, estimated life expectancy of ≥3 months, and adequate hematologic reserve and hepatic and renal function. Approximately 376 pts will be randomized (3:1:1:3) to receive nemvaleukin 6 μg/kg IV on days 1-5 and pembrolizumab 200 mg IV on day 1 of each 21-day cycle, pembrolizumab monotherapy, nemvaleukin monotherapy, or chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan, or gemcitabine) and stratified according to PD-L1 status, histologic subtype (high-grade vs non–high-grade serous), and chemotherapy (paclitaxel vs other). Pts will continue treatment until disease progression or intolerable toxicity (maximum 35 cycles for pembrolizumab; nemvaleukin can be continued). The primary endpoint is investigator-assessed PFS (RECIST v1.1) in the nemvaleukin/pembrolizumab vs chemotherapy group. Secondary/exploratory endpoints include overall survival, other antitumor measures, safety, health-related quality of life, and pharmacokinetic/pharmacodynamic effects. Clinical trial information: NCT05092360.

6025 Background: Platinum resistant ovarian cancer (PROC) remains a disease of high need. Immune checkpoint inhibitors (ICI) have modest activity. We hypothesized that priming with a hypomethylating agent (HMA) guadecitabine (G) will improve the anti-tumor activity of ICI in PROC by enhancing tumor cell recognition by CD8+ T cells. Methods: This open-label phase II study used a Simon’s two-stage design. Eligible patients (pts) had recurrent PROC; ECOG PS of 0-1; normal end organ function; and measurable disease. Up to 5 prior cytotoxic regimens were allowed. Treatment consisted of G 30mg/m2 sq D1-4 and pembrolizumab (P) 200mg iv D5. Each cycle was 21 days. The primary endpoint was response rate (RR). Secondary endpoints were progression-free survival (PFS), clinical benefit rate (CBR), and toxicity assessment. Translational endpoints were LINE1 methylation in PBMCs, global tumor methylation, and immune endpoints. Tumor biopsies were obtained at baseline and after 2 cycles. If 2 patients experienced clinical benefit in stage I [n = 16], enrollment proceeded to stage II. The null hypothesis was rejected for ≥ 6 responses in 35 evaluable patients. Results: 48 pts were enrolled, 43 were treated, and 33 were evaluable for response. Histology was serous (35), endometrioid (2), clear cell (3) and other (3). Median age was 63 (range 40-88) and median number of prior regimens was 4 [range 1-8]. Two PRs were recorded in the first stage, allowing second stage of enrollment. Overall, there were 2 PRs (RR = 6.6%) and 16 pts had stable disease (SD) [48%]. The clinical benefit rate (PR + SD > 3 months) was 27%. One patient continued treatment for > 2 yrs. Grade 3-4 related toxicities were neutropenia [20], lymphopenia, (9), anemia (2), neutropenic fever (1), rash (1), and others (8). There were 13 grade 3-4 SAEs and 4 grade 5 SAEs, assessed as being unrelated to treatment. LINE1 was hypomethylated in PBMCs D5 vs. D1 (n = 21, p = 0.001). Epic arrays measured global tumor methylation, with 39579 CpG sites (0.05%) being differentially methylated (C2D5 vs. C1D1, n = 11, paired t-test; p < 0.01). Main pathways affected included endosomal transport, K+ transport, cathecolamine secretion, etc. PDL1 staining in archival tissue showed tumor staining > 0 in 16 of 35 and tumor/stroma interface staining > 0 in 20 of 35 specimens. Antigen-specific cytotoxic T cell activity was increased in CD8+ cells from ascites (C2D5 vs. C1D1). Conclusions: G+P has modest anti-tumor activity in patients with PROC, but some patients experienced prolonged disease stabilization. Biomarkers of response are being investigated. Clinical trial information: NCT02901899.

Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer

Background: XB002 is an antibody drug conjugate (ADC), with a high affinity human mAb directed against tissue factor (TF) conjugated to a novel cytotoxic agent (payload), ZLA (Zymelink Auristatin). TF is a protein overexpressed in many solid tumors and is associated with disease progression and poor prognosis. XB002 binds to TF without interfering with the coagulation pathway. With its mechanism of action, XB002 has been designed to improve the therapeutic potential of ADCs targeting TF and has demonstrated activity in several solid tumor xenograft models. The purpose of this ongoing first-in-human study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity (anti-drug antibodies) and preliminary antitumor activity of XB002. Presented here is the trial design. Methods: This is a phase 1, non-randomized, open-label, multicenter, dose-escalation and dose expansion study (NCT04925284). Patients must be ≥18 years old and have an ECOG performance status of 0-1 and adequate organ and marrow function. Patients will be treated until radiographic progression per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or unacceptable toxicity. The dose-escalation stage will use a modified i3+3 design; patients with advanced solid tumors (~21 patients) will receive XB002 IV once every 3 weeks. The primary endpoint for dose escalation is the maximum tolerated dose (MTD)/recommended dose (RD) of XB002 per Cohort Review Committee. The MTD/RD will be further evaluated in multiple tumor-specific expansion cohorts of advanced solid tumors (~30 patients per cohort) using a Simon’s 2-stage design. Tumor-specific cohorts (number of prior lines of systemic therapy for advanced disease) include: non-small cell lung cancer (≤3); urothelial cancer (≤3); platinum-resistant epithelial ovarian cancer (≤3); cervical cancer (≤2); squamous cell carcinoma of head and neck (≤3); and pancreatic cancer (1-2). Patients must have measurable disease per RECIST v1.1 and had radiographic progression during or after their last systemic therapy. The primary endpoint for cohort expansion is objective response rate per RECIST v1.1 by investigator. Additional endpoints include safety/tolerability, XB002 pharmacokinetics and immunogenicity, duration of response and PFS per RECIST v1.1 by investigator, overall survival, and changes in tumor markers from baseline. Citation Format: Melissa Johnson, Susanna Ulahannan, Andrae Vandross, Haeseong Park, Leo Faoro, Raffaella Faggioni, Jing Li, Yu-Lin Chang, Shailaja Uttamsingh, Anthony Tolcher. A first-in-human phase 1 study of the safety and pharmacokinetics of XB002 in patients with inoperable locally advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT254.

Background: The MCT inhibitor CYT-0851 potently inhibits MCT1, has activity against MCT4, and blocks lactate transport resulting in cell death in glycolytic cancer cells. In an in vitro CRISPR screen, thymidylate synthetase was a significant hit in 2 resistant cell models, sensitizing them to CYT-0851. Follow-up in vitro combination studies showed that CYT-0851 synergized with 5-FU to inhibit cancer cell growth. Monotherapy clinical activity of CYT-0851 has been reported previously in lymphoma and solid tumors. In the phase 1 dose escalation trial of CYT-0851 plus cape, 400 mg was identified as the recommended phase 2 dose. In three phase 2 trials, cape had a RECIST response rate of 5-8% in ovarian cancer. Methods: An expansion cohort of 10 patients (pts) with platinum resistant advanced ovarian cancer were treated with CYT-0851, 400 mg QD in combination with cape, 1000 mg/m2 PO BID x 14 days every 21 days and were evaluable. One additional pt treated at the 300 mg dose level was evaluable and added to the analysis. The primary objective was safety, and secondary objectives were pharmacokinetics and preliminary anti-tumor activity by RECIST. Results: As of Aug 21, 2023, 11 pts were treated and evaluable, 9 white, 1 African American black, and 1 American Indian or Alaskan native, with a median age of 64 (range 52-76). Median prior therapies were 6 (range 2-14). All but one had 3 or more prior therapies. Median CYT-0851 dose compliance with continuous daily dosing was 99% (range 91– 100%). There were no treatment discontinuations or CYT-0851 dose reductions for treatment related adverse events. 7 pts (64%) experienced a treatment-related adverse event, all were Grade 1-2. There were no grade 3+ treatment related adverse events. The most common related AEs were fatigue reported in 5 pts (46%), and decreased appetite, diarrhea, nausea, palmar-plantar erythrodysaesthesia syndrome and vomiting, each reported in 2 patients (18%). Exposure of CYT-0851 in combination with capecitabine exhibits dose proportional behavior and was similar between combination therapy and monotherapy. One pt had a confirmed PR with progression on day 294, and 2 additional pts achieved a PR that has not been confirmed yet, with treatment ongoing on day 113 and 41. 7 pts had SD, and one patient PD as best response. The disease control rate was 91%. 5 Pts discontinued for progressive disease with a median of 133 days of treatment (range 43-300), and 2 withdrew consent on days 131-134. 4 patients continue therapy on days 42,47,106, and 113. Median PFS was 170 days (95% CI 79-NA). Conclusions: The oral outpatient combination of CYT-0851 and cape has demonstrated an acceptable safety and tolerability profile without any unanticipated toxicities at clinically active doses. The disease control rate of 91% and unconfirmed response rate of 27% in refractory platinum resistant ovarian cancer is promising and warrants further exploration. Furthermore, this regimen should be evaluated in other tumor types commonly treated with 5-FU, including breast and colorectal cancer. Citation Format: Elizabeth Swisher, Gerald Steven Falchook, Pamela N. Munster, Nina Beri, Kathleen N. Moore, Timothy A. Yap, David R. Spigel, Susan Doleman, William D. Bradley, Thomas J. O'Shea, Markus F. Renschler, Ryan C. Lynch. Phase 1 dose expansion results of CYT-0851, a monocarboxylate transporter (MCT) inhibitor, in combination with capecitabine (cape) in platinum-resistant ovarian cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A13.

BackgroundThere is a medical need in platinum resistant ovarian cancer patients. Median progression-free survival (PFS) is 3.4 months with chemotherapy and 6.7 months with chemotherapy-bevacizumab combination regimens.1 RECIST overall response rate (ORR) is 11.8% and 27.3%, respectively. The ORR is 15.9% for bevacizumab as a monotherapy with a median PFS of 4.4 months.2MethodsNCT03596281 An open-label phase 1b trial with a modified toxicity probability interval design to evaluate the combination of a flat dose of 400mg bevacizumab for 6 cycles and 200mg pembrolizumab until disease progression, unacceptable toxicity or completed 24 months of treatment in patients with platinum resistant ovarian cancer. The primary evaluation criteria is safety, the secondary endpoint is the efficacy.Results19 patients have been enrolled between January 2019 and February 2021 in 6 French centers. Patients‘ characteristics are reported (table 1). No dose limiting toxicities were observed. Grade 3 treatment related adverse events occurred in 3 patients (i.e. arterial thromboembolism, bowel perforation, proteinuria and sepsis). No grade 4/5 toxicities were induced. A median of 7 cycles (range 3–14) were administered. Median follow-up of patients was 4.1 months (1.8–23). The RECIST ORR was 26.3% (1 complete response and 4 partial responses) (table 2). The disease control rate was 78.9%. The time to progression was not yet reached in 6 patients. The ORR was equivalent whether patients have been pretreated or not with bevacizumab (27.3 and 25% respectively) (table 3). The ORR according to the combined positive score (CPS) for the evaluation of PD-L1 was 50.0% for CPS≥10% (n=4), 30.0% for a CPS≥1% (n=10) and 25.0% for CPS<1 (n=8) (table 4).ConclusionsA chemotherapy-free regimen combining pembrolizumab and bevacizumab was well tolerated and showed encouraging results in heavily pretreated platinum resistant ovarian cancer patients independent of their previous challenge with antiangiogenic agents.AcknowledgementsFunding for this research was provided by Fondation Cancer du Luxembourg and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationNCT03596281ReferencesPujade-Lauraine E, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Onco Off J Am Soc Clin Oncol 32,1302–1308 (2014).Cannistra SA, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol Off J Am Soc Clin Oncol 33,5180–5186 (2007).Ethics ApprovalThis study was approved by CPP Sud Méditerranée V institution’s Ethics Board; approval number 18.020 (EudraCT number 2017-004197-34).ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

ARTISTRY-7: A phase 3, multicenter study of nemvaleukin alfa, a novel engineered cytokine, in combination with pembrolizumab versus chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer (326)

3007 Background: Erdafitinib (erda) is an oral selective pan-FGFR tyrosine kinase inhibitor approved to treat locally advanced or metastatic urothelial carcinoma (UC) in adults with susceptible FGFR3/2alt who have progressed during or after ≥ 1 line of platinum containing chemotherapy . FGFRalt are observed across a wide range of malignancies and may function as oncogenic drivers independent of the underlying tumor type. RAGNAR (NCT04083976) is an ongoing phase 2 open label, single arm tumor agnostic trial investigating the efficacy and safety of erda in pretreated adult and pediatric pts with advanced solid tumors and FGFRalt. Here, we report results from a planned IA of RAGNAR. Methods: Pts aged ≥ 6 y with advanced or metastatic solid tumors of any histology (except UC) with predefined FGFR1-4alt (mutations/fusions based on local/central test) and documented disease progression on ≥ 1 prior line of systemic therapy (tx) and no alternative standard tx received oral erda until disease progression or intolerable toxicity. The primary end point is objective response rate (ORR) by independent review committee (IRC). Secondary end points include investigator assessed ORR, duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), PFS, OS, and treatment emergent adverse events (TEAEs). Results: As of the IA data cutoff, 178 pts were treated (median age 56.5 y [range 12-79], median 2 prior systemic tx). Only 9.0% of pts responded to last line of tx prior to study entry. ORR by IRC was 29.2% (95% CI, 22.7-36.5). Investigator assessed ORR was 26.4% (95% CI, 20.1-33.5). Responses were observed in 14 distinct tumor types, including gliomas, thoracic, gastrointestinal, gynecological, and rare tumors (Table). ORR in pts with FGFR mutations vs fusions was comparable (26.8% vs 27.0%, respectively). Median DOR, PFS, and OS were 7.1 mo (95% CI, 5.5-9.3), 5.2 mo (95% CI, 4.0-5.6), and 10.9 mo (95% CI, 7.9-14.3), respectively; DCR was 75.3% and CBR was 48.9%. All pts experienced TEAEs, including 69.1% with grade ≥ 3. Treatment-related serious TEAEs occurred in 7.3% of pts. Conclusions: RAGNAR data show, for the first time, evidence of efficacy for erda in heavily pretreated pts with a variety of hard to treat advanced FGFR+ malignancies, including glioblastoma, pancreatic, and salivary gland cancers. Safety was consistent with the known erda safety profile. Clinical trial information: NCT04083976. [Table: see text]

ObjectivesAnetumab ravtansine is an antibody-drug conjugate consisting of a fully human anti-mesothelin monoclonal antibody conjugated to cytotoxic maytansinoid tubulin inhibitor DM4. Mesothelin is highly expressed in ovarian cancer. This phase...

5557 Background: JSKN003 is a biparatopic HER2-targeting ADC conjugated to a topoisomerase Ⅰ inhibitor with an average DAR of 4, who has preliminarily exhibited promising efficacy and safety in the treatment of PROC (QX Rao, et al. 2024 ESMO). This update presents the latest findings in patients (pts) who were not primary platinum-refractory. Methods: A pooled analysis of pts with PROC was performed from the phase Ⅰ JSKN003-101 trial conducted in Australia (NCT05494918) and phase Ⅰ/Ⅱ JSKN003-102 trial conducted in China (NCT05744427), which enrolled pts with advanced solid tumors to receive JSKN003 monotherapy. Tumor tissue samples were collected for central lab assessment of HER2-expression. Results: As of November 29, 2024, the median follow up time was 6.9 months. A total of 46 PROC pts received JSKN003 Q3W, with 2, 2, 40, 1 and 1 pts in 4.2, 5.2, 6.3, 7.3 and 8.4 mg/kg dose groups, respectively. Median age was 59.0 years, 65.2% had ≥ 3 prior lines of systemic therapy, 80.4% and 63.0% had previously received bevacizumab and PARP inhibitor, 39.1% were classified as HER2-expressing (IHC: 1+/2+/3+), with 21.7%, 10.9% and 6.5% in 1+, 2+ and 3+, respectively; 45.7% as HER2-no-expressing (IHC: 0), and 15.2% had no tissue samples for assessment. For 45 efficacy-evaluable pts, the overall response rate (ORR) was 64.4%, the median progression-free survival (PFS) was 7.1 months, and the 9-month overall survival (OS) rate was 84.9% (Table). JSKN003 demonstrated effectiveness across various HER2 expression subgroups. Notably, for pts with HER2-expression, the ORR reached 72.2%, with a median PFS of 9.4 months. Grade 3/4 treatment-related adverse events (TRAEs) occurred in only 6 (13.0%) pts. Serious TRAE occurred in only 4 (8.7%) pts. No TRAEs led to treatment discontinuation or death. The most common TRAE was Grade 1/2 Nausea (39.1%). Additionally, Grade 1/2 Interstitial lung disease (ILD) was observed in 4 (8.7%) pts, with no cases of Grade 3/4 reported. Conclusions: The maturer updated efficacy data reveal that JSKN003 provided substantial improvement in ORR, as well as benefit in PFS and OS in heavily treated PROC, irrespective of HER2 expression. The well tolerated toxicity with long-term observation was consistent with prior experience. A confirmatory trial (NCT06751485) is ongoing in all comers at any HER2 expression level to further support JSKN003 as a treatment option in this population. Clinical trial information: NCT05494918 and NCT05744427 . Efficacy summary. HER2 IHC Total(n = 45) 1+/2+/3+(n = 18) 0(n = 20) Unknown(n = 7) ORR, % (95% CI) 72.2 (46.5, 90.3) 55.0 (31.5, 76.9) 71.4 (29.0, 96.3) 64.4 (48.8, 78.1) CR, n (%) 2 (11.1) 0 0 2 (4.4) PR, n (%) 11 (61.1) 11 (55.0) 5 (71.4) 27 (60.0) Median PFS, month (95% CI) 9.4 (5.7, NE) 5.6 (4.1, NE) 9.6 (2.6, NE) 7.1 (5.6, 9.7) 9-mo OS Rate, % (95% CI) 83.0 (45.7, 95.6) 100.0 (100.0, 100.0) 85.7 (33.4, 97.9) 84.9 (56.6, 95.4)

e17570 Background: Previous studies have shown that combination therapy of immune checkpoint inhibitors (ICIs) may demonstrate more satisfactory efficacy in patients with ovarian cancer compared to monotherapy. Envafolimab is the first globally approved subcutaneously administered PD-L1 monoclonal antibody, which means there is less hospitalization is required, providing the possibility of live-in care. We aim to assess the efficacy and safety of the combination therapy of envafolimab plus lenvatinib combined with etoposide in patients with platinum-resistant recurrent ovarian cancer. Methods: In this single-arm, open-label study, we recruit patients with platinum-resistant ovarian cancer at the Zhongda Hospital, Southeast University (China). The specific regimen consists of subcutaneous envafolimab at a dose of 400mg, oral lenvatinib (12mg per day for patients weighing ≥60kg; 8mg per day for patients weighing <60kg) once daily on a continuous basis, and oral etoposide at a dose of 50 mg once daily on days 1–14 of a 21-day cycle. Oral etoposide is administered for six to ten cycles. The treatment will continue until disease progression or adverse event. The primary endpoint is objective response rate (ORR) assessed by investigators according to RECIST 1.1 criteria. Disease control rate (DCR), duration of response (DoR), progression free survival (PFS), overall survival (OS) and safety are evaluated as secondary endpoints . Data are summarized by descriptive statistics; time-to event endpoints are analyzed using Kaplan-Meier method. Results: From Jun 18, 2022, to Oct 31, 2023, we screened 16 and enrolled 12 patients. At the data cutoff date (Nov 30, 2023), 5 (41.7%) patients had discontinued the study, and 7 (58.3%) patients remained on treatment. Median follow-up was 8.6 months (IQR: 3.3-17.7). Based on the data collected, Objective responses were achieved in 4 (36.3%; 95% CI 10.9–69.2) of 11 patients who had at least one post-baseline efficacy assessment. DCR was 81.8%( 95% CI 48.2–97.7) and median duration of response was 7.4 months (95% CI 4.2–NA). Median progression-free survival was 9 months (95% CI 5.5–NA) and median OS was not reached. The most common grade 3 or 4 adverse events were leukopenia (2 [16.7%]) and thrombocytopenia (2 [16.7%]). No serious adverse events and treatment-related deaths were recorded. Conclusions: The combination of envafolimab plus lenvatinib combined with etoposide shows promising efficacy and manageable toxicities in patients with platinum-resistant ovarian cancer. Clinical trial information: NCT05422183 .