Prior Lines Of Therapy Research Articles

Interim results from the ELiPSE-1 study: A phase 1, multicenter, open-label study of CNTY-101 in subjects with relapsed or refractory CD19-positive B-cell malignancies.

7023 Background: CNTY-101 is an allogeneic, iPSC-derived anti-CD19 Chimeric Antigen Receptor NK (CAR-iNK) cell product with Allo-Evasion edits to avoid host rejection. Potential benefits of CNTY-101 include immediate availability for treatment, repeat dosing without the need for lymphodepletion, and the potential for improved safety over T-cell based therapies. The first-in-human Phase 1 clinical trial of CNTY-101, ELiPSE-1 (NCT05336409), evaluates safety, preliminary efficacy, PK, and translational biomarkers in patients with CD19-positive B-cell malignancies. Methods: Subjects with R/R aggressive and indolent B-cell NHL received lymphodepletion (LDC) followed by assignment to 100e6, 300e6 or 1e9 cells at either Day 1 (Schedule A) or Days 1, 8 and 15 (Schedule B). Eligible subjects (ie, achieved SD or better at Day 28 by PET/CT) can receive additional cycles, with or without one additional regimen of LDC. Subjects also receive daily subcutaneous injections of IL-2 for 8 days (A) or 4 days (B) following each infusion. Results: At time of abstract submission, 10 subjects have been treated (n=4 DL1A; n=3 DL2A; n=2 DL3A; n=1 DL2B). Three subjects (1 at DL1A, 2 at DL2A) received additional cycle(s) of CNTY-101. Three subjects have not yet been evaluated for full safety and efficacy within the DLT window. Seven subjects (n=5 DLBCL; n=1 FL; n=1 MZL) had data available as of the data cut (Nov 30, 2023). All had stage 4 disease, 6/7 were refractory to last line of therapy, with a median of 4 (2-5) prior lines of therapy including CAR T (3/7). No DLTs, GvHD or ICANs were observed. Two subjects had cytokine release syndrome (n=1 Gr 1, n=1 Gr 2), all responding promptly to treatment. ORR/CRR was 25%/25% for 100e6 cells (DL1A) and 67%/33% for 300e6 cells (DL2A). Dose escalation is ongoing. In subjects from all three dose levels, CNTY-101 rapidly traffics out of circulation after infusion and is observed via cell-free DNA on Day 3 and detected up to 28 days. CNTY-101 persistence was not adversely impacted when given without lymphodepletion in two subjects who received additional cycles of CNTY-101. Induction of functional humoral immunogenicity against CNTY-101 was not observed at any of the dose levels, regardless of single or multiple cycles of CNTY-101. Adaptive immune responses were observed in the tumor microenvironment on Day 8. Conclusions: CNTY-101 administered as a single dose in multiple cycles has demonstrated a manageable safety profile and preliminary evidence of efficacy. Allo-Evasion edits may allow for repeat dosing for multiple cycles without allorejection in the absence of lymphodepletion. Preliminary efficacy supports dosing at higher dose levels and with more dose-intense regimens. Updated safety, efficacy, PK, and CNTY-101's impact on tumor for DL3A and DL2B will be provided. Clinical trial information: NCT05336409 .

Clinicopathologic and genomic characteristics of patients with advanced ovarian, breast, and prostate cancer treated with poly (ADP-ribose) polymerase inhibitors (PARPi) in a real-world setting.

3159 Background: PARPis induce synthetic lethality in tumors that have homologous repair deficiencies (HRD). Due to relative rarity of HRD-related genomic and germline alterations across solid malignancies, it remains unclear which patients (pts) may derive most benefit from PARPis across different tumor types. Methods: We analyzed clinicopathologic and genomic characteristics of pts with advanced ovarian (OC, n=33), prostate (PC, n=28) and breast cancer (BC, n=13) treated with PARPi monotherapy at our institution. Only pts with HRD-related pathogenic alterations detected via next-generation sequencing of tumor tissue, with or without genetic susceptibility testing, were included. Results: Forty-one (55%) pts had a confirmed germline HRD-related gene alteration, of which 33 had BRCA1/2 and 8 had non-BRCA1/2 gene alterations. Average age of pts with BC was 54 years, OC 62 years, and PC 68 years. Median number of prior lines of therapy in the advanced setting was 1 (1-4) for OC and BC (0-7) and 3 (1-6) for PC. Median time to progression (TTP) in pts with OC was 8.3 months, BC 4.9 months and PC 3.6 months, likely due to i) majority of pts with OC received maintenance PARPi following favorable response to first-line chemotherapy, ii) pts with PC were older, and iii) more pts with PC had somatic rather than germline HRD-related mutations. Pts with germline vs somatic HRD mutation had longer median TTP in PC (5.0 vs 3.3 months) and BC (6.1 vs 4.0 months), but the opposite was true for OC (7.9 vs 10.8 months). Pathogenic TP53 mutations were identified in all but one pt with OC (32/33), 10/13 pts with BC, and 6/28 PCs. [table] Average TP53gene variant allele fraction (VAF) was similar in OC and BC (49.8% and 51.1%, respectively) but significantly lower in PC (26.4%), suggesting that TP53 mutations in PC were subclonal. No specific TP53 VAF or HRD-to- TP53 VAF ratio cut-off was associated with TTP or overall survival in any of the 3 cancer types. In addition, 7/28 (25%) of pts with PC had PTEN loss associated with modified response to PARPis, whereas none of the pts with BC had PTEN loss and only 3/13 had alterations of the PTEN/PI3K/AKTpathway. Conclusions: Double-strand DNA breaks caused by synergistic effects of aberrant TP53 and HRD-related genes can possibly explain the more favorable response of pts with OC and BC to PARPi, compared to those with PC. Co-alterations in other signaling pathways, epigenetic factors and/or tumor microenvironment likely play a role in the degree of response to PARPis, rather than TP53 clonality alone. In the era of expansion of genomic testing and new indications for PARPi larger genomic studies are needed to identify biomarkers of response to PARPi beyond HRD. [Table: see text]

Preliminary results from a phase 1 study of AC699, an orally bioavailable chimeric estrogen receptor degrader, in patients with advanced or metastatic breast cancer.

3074 Background: Endocrine therapy is a critical component of treatment for over 200,000 patients diagnosed yearly with estrogen receptor positive (ER+)/HER2- breast cancer. Although selective ER degraders (SERDs) have improved progression-free survival in this patient population, as monotherapy they have shown very limited overall response rates (ORR). AC699 is a novel chimeric degrader that binds, ubiquitinates and degrades ERα by bringing it into close proximity with an E3 ligase. This mechanism of action may result in greater specificity and more complete target blockade compared to SERDs. Initial results from the ongoing first-in-human dose escalation study of AC699 (NCT05654532) are presented here. Methods: The study employed a 3+3 design, with the option of adding backfill patients to each cohort cleared and deemed safe. Patients must have had locally advanced or metastatic ER+/HER2- breast cancer and received at least 2 prior lines of endocrine treatment, or at least 1 prior line if combined with a CDK4/6 inhibitor. AC699 was administered orally once daily in 28-day cycles. Tumor responses were assessed every 2 cycles using RECIST v1.1 criteria. The relationship between ESR1 mutational status and anti-tumor activity was investigated as an exploratory analysis. Results: A total of 22 patients had received AC699 in 3 dose cohorts (100, 200 and 300 mg) at the time of data cutoff. The median age was 61 years and the median lines of prior therapy was 5 (range 2-10). Prior treatments included CDK4/6 inhibitor (100%), aromatase inhibitor (91%), fulvestrant (82%), novel oral SERD or covalent antagonist (SERCA) (23%), and ER chimeric degrader (14%). Eighteen patients had measurable disease while 4 had bone lesions only. There were no dose-limiting toxicities, dose reductions or discontinuations for treatment-related AEs, and the maximum tolerated dose was not reached. The most common treatment-emergent AEs were fatigue (23%), dehydration (18%) and nausea (18%). All treatment-related AEs were Grade 1 or 2, including nausea (18%) and hot flushes (14%). Fifteen patients had at least 1 scan before the data cutoff date and of these, 3 were not evaluable for ORR due to having bone lesions only. Among the 12 evaluable patients, 4 (33%) achieved partial response: 3 confirmed and one unconfirmed. The clinical benefit rate (CBR) which also includes patients with stable disease ≥24 weeks was 42% (5/12). In the subgroup of evaluable patients harboring a confirmed ESR1 mutation, the ORR was 67% (4/6), the CBR was 83% (5/6) and the median time on treatment was 168 days (range 56-336), with 4 of 7 patients still receiving AC699. Conclusions: Preliminary data from the ongoing phase 1 trial evaluating AC699 indicate promising safety, tolerability, and anti-tumor activity, at doses up to 300 mg orally once daily. A phase 2 study will begin enrolling in early 2024. Clinical trial information: NCT05654532 .

Associations of T-cell fitness prior to B-cell maturation antigen (BCMA)–targeted chimeric antigen receptor T-cell (CART) and bispecific T-cell engager (BiTE) therapies and efficacy/toxicity in relapsed/refractory multiple myeloma (RRMM).

7549 Background: While CART and BiTE have led to unprecedented responses in RRMM, some patients (pts) do not respond or have short-lived responses. Currently no predictive markers exist to identify these pts. This study explored pretreatment T-cell fitness and efficacy/toxicity in RRMM using a novel single-cell secretome analysis. We hypothesized that pretreatment Polyfunctional Strength Index (PSI) may predict efficacy to BCMA-directed T-cell therapies. Methods: We included 14 RRMM pts treated with idecabtagene vicleucel or teclistamab at Yale Cancer Center with ≥6 mos post-treatment follow-up. Peripheral blood prior to treatment was frozen and then PBMC’s thawed for analysis. PSI, a metric for T-cell fitness combining polyfunctional T-cells % with the intensity of secreted cytokines, was obtained using the IsoPlexis’ Single-Cell Secretome Platform. The overall PSI was an average of CD4+ and CD8+ PSIs. Response was assessed by the International Myeloma Working Group criteria and response duration was defined as time from response to disease progression. Responder (R) was defined as ≥very good partial response for ≥6 mos. Non-responder (NR) was defined as stable or progressive disease ≤3 mos. Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) were graded using the American Society for Transplantation & Cellular Therapy system. Statistics were performed with Mann-Whitney U test using GraphPad PRISM v.9. Results: There were 7 pts in R group (2 BiTE & 5 CART) and 7 pts in NR group (3 BiTE & 4 CART). Median follow-up time was 13.5 mos(range, 7-27). Median age at treatment was 64 yrs in R and 63 yrs in NR. Extramedullary disease (EM) was present in 14.3%(n=1) in R and 71.4%(n=5) in NR. High-risk cytogenetics, defined as del17p, t(4;14), t(14;16), t(14;20), 1q gain/amplification and del1p, were seen in 42.9%(n=3) in R and 85.7%(n=6) in NR. Median prior lines of therapy was 6(range, 4-9) in R and 8(range, 4-10) in NR. CRS/ICANS occurred 85.7%(n=6) in R and 28.6%(n=2) in NR. Overall PSI was 184 in R and 91 in NR(p=0.1649). CD4+ PSI was 160 in R and 75 in NR(p=0.1649). CD8+ PSI was 207 in R and 108 in NR(p=0.1981). Overall PSI was 143 in CRS/ICANS and 130 in no CRS/ICANS(p=0.7546). Conclusions: Overall PSI, CD4+ PSI and CD8+ PSI were 1.9-2.1 times higher in R compared to NR and overall PSI was slightly higher in CRS/ICANS compared to no CRS/ICANS though the difference was not statistically significant. One limitation was a small sample size and thus testing PSI in a larger cohort might yield statistically significant results. The NR group had more high-risk cytogenetics and higher EM. One confounder could be that measuring peripheral T-cell fitness may not be sufficient to predict response in EM where spatial determinants of T-cell influx play a role.

A CRISPR-edited allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout (CB-010) in patients with relapsed/refractory B cell non-Hodgkin lymphoma (r/r B-NHL): Updated phase 1 results from the ANTLER trial.

7025 Background: CB-010 is an allogeneic anti-CD19 CAR-T cell therapy derived from healthy donor T cells using CRISPR hybrid RNA-DNA (chRDNA) technology. This technology is used to introduce 3 genome edits: (1) knockout of TRACto eliminate TCR expression and reduce risk of GvHD, (2) insertion of a CD19-specific CAR (scFv FMC63) into the TRAC locus, and (3) knockout of PD-1 to prevent premature CAR-T cell exhaustion and potentially enhance antitumor activity. Methods: ANTLER is a Phase 1 clinical trial (NCT04637763) with a 3+3 dose escalation phase and a dose expansion phase designed to evaluate safety, tolerability, and antitumor activity of CB-010 in patients (pts) with r/r B-NHL and determine RP2D. In dose escalation, pts must have received ≥2 prior lines of chemoimmunotherapy or had primary refractory disease to 1L therapy. Pts received lymphodepletion with sequential cyclophosphamide (60 mg/kg/day x 2 days) and fludarabine (25 mg/m2/day x 5 days) followed by a single CB-010 infusion. Results: 16 pts with r/r B-NHL (10 LBCL, 3 MCL, 2 FL with POD24, 1 MZL) received CB-010 at 40 x 106 CAR-T cells (dose level 1; N=8), 80 x 106 CAR-T cells (dose level 2; N=5), or 120 x 106 CAR-T cells (dose level 3; N=3) during dose escalation. Median age was 66 years (range 55-82). Median time since first diagnosis was 2.4 years (range 0.2-16.4). Median prior lines of therapy was 2 (range 1-8). CB-010 was generally well tolerated. No GvHD was seen. CRS occurred in 7/16 (44%) pts (no CRS grade ≥3). Median time to CRS onset was 3.5 days and median duration was 3 days. ICANS occurred in 4/16 (25%) pts (13% grade ≥3). Median time to ICANS onset was 7.5 days and median duration was 2 days. The 3 most common TEAEs grade ≥3 were thrombocytopenia (11/16; 69%), neutropenia (9/16; 56%), and anemia (8/16; 50%). One grade 3 infection (antecubital cellulitis) occurred unrelated to CB-010. After a single CB-010 infusion, 15/16 (94%) pts achieved an overall response, 11/16 (69%) achieved a CR, and 7/16 (44%) achieved a CR at ≥6 months. Median time to CR was 28 days. Among LBCL pts (n=10), 9 (90%) achieved an overall response, 7 (70%) achieved a CR, and 5 (50%) achieved a CR at ≥6 months. To date,2 pts have completed the 24-month study period with ongoing CR. Peak expansion of CB-010 occurred at days 7-10 post-infusion. T and NK cells recovered rapidly in peripheral blood (<3 weeks) after lymphodepletion, and B cells remained below the limit of quantification beyond 3 months, supporting specific targeting of B cells by CB-010. Conclusions: CB-010 showed a manageable safety profile and promising efficacy for treatment of pts with r/r B-NHL, including aggressive subtypes. The dose escalation phase is complete. Enrollment of 2L LBCL pts in dose expansion is ongoing. Initial dose expansion data at the CB-010 RP2D and translational data will be presented for the first time at the meeting. Clinical trial information: NCT04637763 .

MagnetisMM-30: A phase 1b, open-label study of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma (RRMM).

TPS7577 Background: Elranatamab (ELRA) is a humanized B-cell maturation antigen (BCMA)–CD3 bispecific antibody (BsAb). Single-agent ELRA induced deep and durable responses with a manageable safety profile in patients (pts) with RRMM enrolled in the phase 2 registrational MagnetisMM-3 study (NCT04649359; Lesokhin et al, Nat Med 2023). Iberdomide (IBER) is a novel CELMoD[TM] agent that induces enhanced antimyeloma tumoricidal and immunomodulatory activity in pts with RRMM (Lonial et al, Lancet Haematol 2022). While IBER in combination with ELRA has not been evaluated clinically, it may provide additional benefit to pts with RRMM based on the mechanisms of action of this novel combination. Methods: MagnetisMM-30 is a phase 1b, open-label, prospective study evaluating the safety, efficacy, and pharmacokinetics of ELRA in combination with IBER in pts with RRMM. The study has 2 parts: Part 1 for dose-escalation and Part 2, randomized for dose optimization. After 2 step-up priming doses of ELRA, pts will receive subcutaneous ELRA weekly with IBER given daily for 21 days of each 28-day cycle. After ≥6 months (cycles) of treatment, pts with a partial response or better for ≥2 months are eligible for reduced dosing frequency of ELRA. Once the 2 combination dose levels (dose levels A and B) are selected from Part 1 as the recommended phase 2 doses for ELRA and IBER, pts in Part 2 will be randomized 1:1 (stratified by the number of prior lines of therapy [LOTs; 1 vs >1]) to dose levels A and B. Key inclusion criteria are pts aged ≥18 years with a MM diagnosis per IMWG criteria, Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and bone marrow function, and disease relapsed or refractory to the last antimyeloma regimen per IMWG response criteria. Pts who received 2-4 or 1-3 prior LOTs, including ≥1 immunomodulatory drug (IMiD) and ≥1 proteasome inhibitor (PI), are eligible for Parts 1 and 2, respectively. All pts must have received ≥2 consecutive cycles of an IMiD-containing regimen and ≥2 consecutive cycles of a PI or PI-containing regimen. Key exclusion criteria are pts with stem cell transplant ≤12 weeks prior to enrollment; active, uncontrolled infection; prior treatment with BCMA-directed or CD3 redirecting therapy or prior CELMoD agents (ie, IBER or mezigdomide). This study is ongoing; Part 1 and Part 2 will enroll approximately 27 and 60 pts, respectively. Study endpoints are listed in the table. Clinical trial information: NCT06215118 . [Table: see text]

A study of a new mechanism: Intracellular retention allo-CART safety and efficacy for extranodal bulky B-NHL.

e19007 Background: Extranodal bulky lesions, a significant adverse prognostic factor in lymphoma, commonly denote a more aggressive disease course, mandating prompt and intensified treatment strategies. In response, we developed ThisCART19A, a non-genetic editing and off-the-shelf anti-CD19 CAR T-cell therapy incorporating intracellular retention of membrane proteins, representing a novel approach that downregulates surface expression of TCRαβ/CD3 complexes. ThisCART19 has exhibited a favorable safety profile and promising efficacy in patients with relapsed/refractory bulky B-cell Non-Hodgkin Lymphoma. Methods: This is an investigator-initiated trial employing an open-label, dose escalation, and expansion design to evaluate the safety and efficacy of ThisCART19A in patients with relapsed or refractory bulky B-cell non-Hodgkin lymphoma (B-NHL). Bulky disease was defined as the longest diameter of the mass >5 cm at baseline. Results: Between June, 2021, and June, 2023, 13 extranodal bulky disease were enrolled in the studies and successfully received ThisCART19A. The median age was 56 (range, 37~67) years. All 13 patients had 3 median prior lines of therapy (range, 2-5). All patients received anti-CD20 and multi- agent chemotherapy. 8 (61.54%) patients had prior auto CART. mSPD was 48 (range, 16~162) cm². mTMTV was 114.9 (range, 14~483) ml. As of February 2024, The most common adverse events were CRS (100%) , infections (30.77%), ICANS (23.08%) and cytopenias(100%); This is no grade 3 or higher CRS occurred;only 1(7.69%)patient experienced grade 4 ICANS and relieved after intravenous dexamethasone treatment. This is no treatment-related deaths occurred. Among the 13 patients, 10 were evaluable, with an ORR and CR of 90% and 80%, respectively, at 28 days post-infusion. mPFS was 62 days (range, 28~227). The patient who achieved a PR received chemotherapy and radiotherapy as consolidation, As of February 5th, 2024, the patient has survived for 263 days and is still under follow-up. Additionally, two patients progressed after CR received sequential chemotherapy and BCL-2 Inhibitor, with an average OS of 326.5 days, still being under follow-up. In 13 evaluable patients, the mean C-max was 1043.13 cells/μL(range, 0.59~10045.4), and the mean AUC0-28d was 1542.23 cells/μL × day(range, 0.91~11724).In this cohort, two patients received low-dose infusions at 1×106 cells/kg and still achieved excellent expansion, the respective C-max were 726.432 cells/μL and 336.67 cells/μL. Conclusions: This CART19A exhibited favorable safety, remarkable expansion potential, and efficacy profiles in the treatment of r/r bulky lymphoma. Notably, it achieved a high ORR of 90%, providing a favorable window of opportunity for subsequent consolidation and intensification treatments. Moreover, this transition from a bulky to a non-bulky disease state reduces the intricacy of follow-up treatments. Clinical trial information: NCT04384393 .

A multicenter real-world study on the efficacy and safety of anlotinib-based treatment for metastatic breast cancer.

e13120 Background: Anlotinib is a multi-targeted small molecule receptor tyrosine kinase (RTK) inhibitor that inhibits angiogenesis. There is only one phase II study on the use of anlotinib in advanced breast cancer (MBC). Therefore, this study aims to analyze its efficacy and safety in the treatment of BC in the real world. It has been approved for the treatment of advanced non-small cell lung cancer and soft tissue sarcoma. There is limited research on the use of anlotinib in advanced breast cancer (MBC). Methods: This study retrospectively analyzed the clinical data of MBC patients who received anlotinib treatment at four domestic centers from January 2021 to December 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Kaplan-Meier analysis was used to analyze PFS and OS, and Cox regression model was used to analyze the hazard ratios (HRs) of anlotinib-based treatment on PFS and OS in different subgroups of patients. A p-value <0.05 was considered statistically significant. Results: A total of 153 MBC patients receiving anlotinib-based treatment were included from four centers. The median age was 51 years (range: 22-76), and the median number of prior lines of therapy was 3. The median PFS was 7.7 months (range: 5.2-10.1 months), and the median OS was 28.0 months (range: 21.4-34.9 months). The median ORR and DCR were 19.6% and 60.1%, respectively. The ORR for HR+/HER2- and triple-negative breast cancer patients was 11.6% and 28.8%, respectively, DCR for HR+/HER2- and triple-negative breast cancer (TNBC) patients was 55.8% and 59.6%, respectively. The median PFS was 9.0 months (range: 6.0-11.9 months) for HR+/HER2- patients and 5.3 months (range: 3.5-7.0 months) for TNBC patients, while the median OS was 33.0 months (range: 24.4-41.5 months) and 14.0 months (range: 9.5-18.4 months), respectively. In the subgroup analysis, age <60 years, initial stage IV disease, Ki67≤60%, and treatment with PD-L1 monoclonal antibodies-based regimen were associated with PFS benefit. ECOG <2 and treatment with PD-L1 monoclonal antibodies-based regimen were associated with prolonged OS. Among the 31 patients with brain metastases receiving anlotinib treatment, 11 had active brain metastases and 20 had stable brain metastases. The median PFS was 8.0 months. The intracranial ORR was 12.9%, and the intracranial DCR was 61.3%. No serious adverse events or treatment-related deaths occurred. Grade I/II adverse reactions included hand-foot syndrome (22.2%) and fatigue (19.6%), while grade III/IV adverse reactions included fatigue (6.5%) and decreased neutrophil count (5.2%). Three patients required dose reduction due to intolerable adverse reactions, and nine patients discontinued treatment. Conclusions: Anlotinib demonstrates good antitumor activity and safety in the treatment of MBC. When combined with chemotherapy or immunotherapy, it can improve PFS and OS without significantly increasing toxicity. In particular, it shows promising intracranial ORR and PFS in patients with brain metastases. Clinical trial information: NCT04541420 .

Preliminary results from a phase I study of IMM0306 in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma.

7060 Background: IMM0306 is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα on both heavy chains. It exerts excellent cancer killing efficacy by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcɣR engagement. Here, we report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy results of phase I study in patients (pts) with relapsed or refractory (R/R) CD20-positive B-cell non-Hodgkin's lymphoma (B-NHL). Methods: Eligible pts with R/R CD20-positive B-NHL were enrolled in this multicenter phase I study (NCT05805943). IMM0306 was administered as monotherapy at escalating doses of 0.04, 0.1, 0.25, 0.5, 0.8, 1.2, 1.6, 2.0 mg/kg intravenously once a week until disease progression or intolerable toxicity. Dose-limiting toxicity (DLT) was evaluated in the first 28 days. Safety was evaluated per CTCAE 5.0, PK and PD analysis were also assessed, tumor assessments performed once every 8 weeks by Lugano 2014 criteria. Results: As of Nov 21, 2023, 48 pts were enrolled. The median age was 56 years with 30 (62.5%) males. The median prior lines of therapy were 2. All pts received previous anti-CD20 therapy. No DLTs were observed. Recommended phase II dose was determined as 2.0 mg/kg. The most frequent treatment related adverse events (TRAEs) were WBC decreased (66.7%), anemia (64.6%), lymphocyte decreased (58.3%), ANC decreased (47.9%), PLT decreased (45.8%), infusion-related reactions (35.4%). ≥grade 3 TRAEs occurred in 33 (68.8%) pts, with the most common being lymphocyte decreased (56.3%), WBC decreased (18.8%), ANC decreased (18.8%). 8 (16.7%) pts experienced treatment related serious adverse event. Discontinuation due to AEs occurred in 1 pt (grade 4 PLT decreased at 1.6mg/kg without bleeding). No AE led to death. IMM0306 exhibited approximate dose-proportional increase in PK exposure from 0.5 to 2.0 mg/kg and no obvious accumulation was observed after repeated dosing. At 1.2 mg/kg and higher dose, CD47 receptor occupancy on peripheral lymphocytes was saturated, suggesting IMM0306 is well tolerated from perspective of CD47 engagement. B-cell depleted rapidly at doses ≥ 0.8 mg/kg. Elevated cytokines levels were observed after first dosing of IMM0306, but multiple dosing did not stimulate further cytokine activation. Among 33 pts who received doses ≥ 0.8 mg/kg, 5 CR (4 follicular lymphoma [FL], 1 marginal zone lymphoma [MZL]), 5 PR (3 FL, 1 MZL, 1 diffuse large B cell lymphoma) and 11 SD were seen; the median PFS was 10.58 months (95% CI, 2.2, NA) and the median OS was not reached. Among 17 FL pts, 7 (41%) responded including 4 CR and 3 PR; among 6 MZL pts, 2 (33.3%) responded including 1 CR and 1 PR. Conclusions: IMM0306 was well-tolerated and with promising preliminary anti-tumor activity especially in pts with R/R FL and MZL. The phase Ⅱ study is ongoing. Clinical trial information: NCT05805943 .

SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer.

TPS8657 Background: Most patients (pts) with advanced non-small cell lung cancer (NSCLC) will receive treatment with immunotherapy and develop tumor resistance. Several trials investigating combination therapy have not shown benefit over chemotherapy. Additional therapeutic options are needed. Complex clinical trials increase barriers to enrollment. Pragmatic trial designs may overcome challenges with accrual and representativeness in the appropriate setting. S1800A was a randomized phase II trial within Lung-MAP that showed a statistically significant improvement in overall survival (OS) with PR versus SOC for pts with advanced NSCLC who had tumor progression on prior chemotherapy and immunotherapy (JCO 2023). As a follow-on, we designed a pragmatic, randomized, registration intent trial to validate OS results and enhance representative accrual reflecting real-world practice. Methods: S2302 is a registration-intent randomized trial for pts who previously received PD-(L)1 inhibitor therapy for at least 84 days and platinum-based therapy, stratified by immediate prior line of therapy including PD-(L)1 inhibition (yes/no) and PS (0/1 v. 2). Pts are randomized to PR or investigator’s choice SOC (recommended to be based on NCCN guidelines). The primary objective is to compare OS between the arms. The only secondary objective is to summarize serious and unexpected high-grade (Grade 3-4) treatment-related adverse events and all Grade 5 adverse events. The accrual goal is 700 pts based on a design with 85% power to detect a hazard ratio of 0.77, using a 1-sided 2.5% level log-rank test. Estimated accrual duration is 24 months. As of January 2024, 286 pts were randomized, and enrollment is ongoing. S2302 Pragmatica-Lung presents a novel and potentially practice-changing paradigm to conduct a study with a combination of FDA approved drugs with well-known safety profiles and limited toxicity overlap. There are no onerous radiology or specimen requirements, and SOC treatment is provided as per FDA-approved package inserts and institutional policies. The goal is to empower practicing clinicians to enroll pts they see every day by reducing the study barriers and burden of clinical trial participation. The resulting pts enrolled will be more representative than other registration-intent trials. This approach allows the trial to reach more patients and holds the potential to better inform the field across a more representative set of pts with broader impact. Clinical trial information: NCT05633602 .

ARTEMIS-001: Data from a phase 1a/b study of HS-20093 in patients with relapsed small cell lung cancer (SCLC).

8093 Background: SCLC is characterized by a high rate of proliferation and poor prognosis, and new therapies are urgently needed. B7-H3 is highly expressed in SCLC. HS-20093, a B7-H3-targeted antibody-drug conjugate (ADC), demonstrated antitumor activity in advanced solid tumors in the dose escalation part of ARTEMIS-001 study (Jie Wang et al., JCO, 2023) (NCT05276609). Here, we present results on the efficacy and safety of the expansion doses in patients (pts) with SCLC from phase 1a/b. Methods: ARTEMIS-001 study consisted of dose escalation (1a) and expansion (1b) part. Pts were treated with doses of 1.0 to 16.0 mg/kg HS-20093 every 3 weeks in dose escalation, and were treated with doses at 8.0 mg/kg and 10.0 mg/kg randomly in dose expansion. Pts with SCLC were required to have received prior platinum-based standard therapy. B7-H3 expression was retrospectively evaluated by IHC. Results: As of data cutoff November 30th 2023, a total of 56 pts with extensive stage SCLC (ES-SCLC) were enrolled and received ≥1 dose of HS-20093 with doses at 8.0 mg/kg (n=31) or 10.0 mg/kg (n=25). Median prior lines of therapy was 2.0 (range: 1-6). All pts received platinum plus etoposide and 73.2% (41/56) received immunotherapy. Safety profile was consistent with previous reports. The most common grade≥3 treatment-related adverse events (≧10%) were neutropenia, leukopenia, lymphopenia, thrombocytopenia and anemia. Out of 56 pts, 52 pts were efficacy evaluable (8.0 mg/kg: 31 pts; 10.0 mg/kg: 21 pts). HS-20093 showed encouraging efficacy in relapsed ES-SCLC (Table). Tumor shrinkage in target lesions occurred in 96.2% (50/52) pts with a post-baseline scan. Deep response defined as tumor shrinkage ≥50% was obtained in 44.2% (23/52) pts. Median overall survival has not yet reached. Responses were observed regardless of B7-H3 expression. Pharmacokinetic (PK) showed approximately dose-proportional increase in exposure with a half-life of 3-7 days. PK profiles of total antibody and ADC were similar and exposure to payload was considerably low. Conclusions: HS-20093 demonstrated promising antitumor activity and manageable safety in pts with previously-treated SCLC. Phase 3 study is planned to compare the efficacy and safety of HS-20093 with standard-of-care chemotherapy in relapsed SCLC. Clinical trial information: NCT05276609 . [Table: see text]

Botensilimab plus balstilimab in microsatellite stable metastatic colorectal cancer: Assessing efficacy in non-liver metastatic sites.

3556 Background: Botensilimab (BOT) is an Fc-enhanced, multifunctional anti-CTLA-4 antibody with unique mechanisms of action. In microsatellite stable colorectal cancer (MSS CRC), previous I-O combinations have shown poorer responses in metastatic sites of disease outside of the lungs and lymph nodes, even in non-liver metastases (NLM) populations. Here we present updated efficacy data with longer follow-up from an expanded phase 1b study (NCT03860272) in patients with NLM MSS CRC treated with BOT and balstilimab (BAL; anti-PD-1). Methods: As of Nov 29, 2023, 77 patients with NLM MSS CRC (median follow-up 13.0 months [range 0.6–42.6]) with ≥6 months follow-up were included (intention to treat [ITT]; all treated); of these, 70 had ≥1 post-baseline scan (efficacy evaluable [EE]). Patients received BOT 1 or 2 mg/kg every 6 weeks (Q6W) and BAL 3 mg/kg every 2 weeks. Endpoints included RECIST 1.1 confirmed objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS). Results: Median age was 56 years (range 36–82), 48% male, and median prior lines of therapy was 4 (range 1–10). ORR was 22% (17/77) and DCR was 73% (56/77), with the median DOR not reached (NR; 95% CI 5.7–NR). An additional response confirmed after the data cutoff (18/77; ORR 23%), with 11/18 responses ongoing. Subgroup analyses revealed that BOT and BAL showed comparable activity (ORR 18–33%) across metastatic sites outside of the lungs, including the peritoneum, soft tissue, pleura, and the brain (Table). One responder with an occult brain metastasis experienced pseudoprogression, followed by a complete systemic response to treatment in target lung lesions. No new safety signals were observed and updated safety and translational data will be presented. Conclusions: In summary, for MSS CRC, BOT and BAL is differentiated from previous I-O combinations by producing deep and durable responses even in difficult-to-treat metastatic sites. In NLM patients, responses were observed in 18–33% of sites of disease including the peritoneum, soft tissue, pleura, and the brain. These compelling results support further investigation in the fully enrolled, randomized, global phase 2 trial in MSS CRC (NCT05608044) and a planned global phase 3 trial. Clinical trial information: NCT03860272 . [Table: see text]

GOG3069: Phase 2 study of alpelisib and fulvestrant for PIK3CA-mutated estrogen receptor (ER)-positive endometrioid endometrial cancers.

TPS5639 Background: Treatment options for persistent, metastatic, or recurrent endometrial cancer continues to evolve as we learn more about the molecular landscape of this disease. Recent studies have shown a benefit to endocrine-based combinations such as aromatase inhibitors with mTOR or CDK4/6 inhibitors especially in patients who had not received prior chemotherapy ( 1– 3). The presence of oncogenic PIK3CA mutations have been shown to impact response to aromatase inhibitors in breast cancer. The combination of alpelisib and fulvestrant was approved for the treatment of metastatic hormone receptor-positive, HER2-negative breast cancer harboring oncogenic mutations in the PIK3CA gene that progressed on prior endocrine therapy( 4). PIK3CA mutations are commonly identified in endometrial cancers and may similarly confer endocrine resistance. GOG3069 is a phase II trial designed to evaluate the efficacy and safety of alpelisib and fulvestrant in a biomarker-selected endometrial cancer patient population. Methods: This is a phase II non-randomized, open label, multicenter, two-stage study. Eligible patients must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent endometrial carcinoma with measurable disease by RECISTv1.1 criteria. Patients cannot be curable by surgery or radiotherapy. Disease must be of endometrioid histology with positive expression of estrogen receptor (defined as ≥1% of tumor cells demonstrating positive nuclear staining by immunohistochemistry) and oncogenic PIK3CA mutation. Patients may have received no more than 3 prior lines of therapy including 1 prior line of systemic chemotherapy. Enrolled patients will receive treatment with alpelisib 300mg orally daily and fulvestrant 500mg IM on Day 1 and Day 15 of Cycle 1, then 500mg IM on Day 1 of each 28-day cycle. The primary endpoint is overall response rate as measured by RECISTv1.1-defined tumor response. Secondary endpoints include safety, tolerability, progression-free survival, duration of response, and 24-month overall survival rate. GOG3069 activated in November 2023 and expects to enroll across 15 US sites. The statistical plan uses a conditional stratified design factoring differing probabilities of response based on whether the patient had prior chemotherapy exposure. ClinicalTrials.gov Identifier: NCT05154487

OBX-115, an interleukin 2 (IL2)-sparing engineered tumor-infiltrating lymphocyte (TIL) cell therapy, in patients (pts) with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma.

9515 Background: Investigational unengineered TIL cell therapy has shown promising activity in ICI-resistant metastatic melanoma but requires systemic high-dose IL2, which has well-described high-grade toxicity frequently requiring specialized management and limiting pt eligibility. OBX-115 autologous engineered TIL cell therapy does not require co-administration of IL2 due to its regulatable expression of membrane-bound IL15 (mbIL15) using the FDA-approved small-molecule drug acetazolamide (ACZ) to provide cytokine support for TIL expansion and persistence. Methods: This Phase 1 study (NCT05470283) assesses the OBX-115 regimen in pts with ICI-resistant unresectable/metastatic melanoma. OBX-115 is manufactured from the pt’s tumor tissue (surgical excision or core needle biopsy [CNB]). After lymphodepletion (cyclophosphamide, fludarabine), pts receive OBX-115 followed by ACZ once daily for up to 7 days; ACZ redosing (up to 7 days) is permitted at Wk 6 for non-responders. No systemic IL2 is administered. Peripheral blood and tumor tissue is collected for longitudinal immune profiling. Results: As of 02 Jan 2024, 9 pts (median age, 50 y) with ICI-resistant metastatic melanoma were infused with OBX-115 (median study follow up, 17 wks; range, 2–58 wks). Median lines of prior therapy was 3 (range, 1–6). OBX-115 was successfully manufactured for all pts, including from CNB tumor tissue (n = 5). The infusion product had a high proportion of CD8+ cells (≥96%) and stem-like cells (CD8+CD39-CD69-; median 76%) with very low PD-1 expression in the CD8+ population ( < 1%). Post-infusion safety included no DLTs, 3 Gr 3 nonhematologic TEAEs in 2 pts (abdominal pain, ALT elevation, syncope), and no Gr 4 nonhematologic TEAEs. ACZ was redosed and well-tolerated in 4 of 5 eligible pts. Among patients with minimum 12-wk follow-up (n = 6), ORR per RECIST v1.1 was 50% (2 CR, 1 PR, 3 SD); all responses occurred between Wk 6–18 and were ongoing, with longest response sustained > 12 mo. One pt developed new metastatic disease (liver) and progressed at Wk 24, despite continued target lesion reduction; no pt developed brain metastasis. Post-infusion ctDNA was not detectable in any of the responders at Day 14 or 42. Though OBX-115 had minimal NK cells ( < 1%), post-infusion peripheral blood and tumor biopsies showed NK cell expansion, consistent with trans-presentation of mbIL15 to circulating NK cells. Updated efficacy data on all infused pts will be presented. Conclusions: OBX-115regulatableengineeredTIL cell therapy was well-tolerated and produced consistently deepening and durable responses, indicating that OBX-115 may mediate CRs and durable clinical benefit in ICI-resistant metastatic melanoma without high-dose IL2. OBX-115 investigation continues in this and an ongoing Phase 1/2 multicenter study (NCT06060613). Clinical trial information: NCT05470283 .

Interim analysis (IA) of the giredestrant (G) + everolimus (EVERO) arm in MORPHEUS Breast Cancer (BC): A phase I/II study of G treatment (tx) combinations in patients (pts) with estrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC).

1059 Background: Endocrine therapy (ET) + a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is a therapeutic mainstay for first-line tx of ER+ mBC. Finding effective ET combinations after progression remains a challenge; however, targeting the Akt/mTOR pathway is a promising approach. G is a highly potent, non-steroidal, oral (PO), selective ER antagonist and degrader that is well tolerated and achieves robust ER occupancy. EVERO is an approved mTOR inhibitor. Here, we present a 16-week IA of the G + EVERO arm in MORPHEUS BC (NCT04802759). Methods: Eligible pts with disease progression on 1–2 lines of ET (including a CDK4/6i) for LA/mBC were randomized 1:6 to receive G (30 mg PO daily [QD]) or G + EVERO (10 mg PO QD) until disease progression (PD)/unacceptable toxicity. The study was not designed to make explicit power and type I error considerations for a hypothesis test. Primary endpoints were safety and objective response rate (ORR); other endpoints included progression-free survival (PFS), overall survival, clinical benefit rate, disease control rate (DCR), duration of response, and pharmacokinetics. Steroid mouthwash was recommended for prophylaxis or treatment. Genetic alterations were defined using baseline circulating tumor DNA. Results: Results for the G arm have been presented previously and are not included here. As of July 24, 2023, 15 pts were enrolled in the G + EVERO arm: 66.7% and 33.3% received 1–2 prior lines of therapy for LA/mBC, respectively; 26.7% had prior fulvestrant, and 73.3% had liver metastasis at enrollment. One pt had prior capecitabine. Safety data are in the table. Confirmed ORR in the G + EVERO arm was 26.7% (n = 4). Partial responses were reported in 26.7% of pts (n = 4; all had ESR1 mutations, 1 also had an Akt pathway mutation), 46.7% of pts (n = 7) had stable disease, and the DCR was 53.3% (n = 8). Median PFS was not reached at data cutoff. No clinically relevant drug–drug interactions were observed. Conclusions: Safety of G + EVERO was aligned with the individual safety profile of each drug with no overlapping toxicities or new safety signals seen. An encouraging efficacy signal was observed with G + EVERO in pts with PD on 1–2 lines of ET (including a CDK4/6i). G + EVERO is being further investigated in the Phase III evERA BC trial (NCT05306340). Clinical trial information: NCT04802759 . [Table: see text]

Exploring T cell subsets as predictors of response to BCMA targeting bispecific antibody therapy in multiple myeloma.

7567 Background: BCMA targeting bispecific Antibody (bsAb) therapy has shown unprecedented response and survival rates in patients with relapsed/refractory multiple myeloma (MM). The clinical activity of bsAb therapy has been shown to depend on T-cell function, yet clinical parameters, such as absolute lymphocyte count (ALC) have not been found to be associated with response to bsAbs. The aim of the present study was to elucidate whether distinct T cell subsets, such as CD4 and CD8 counts as well as their proportion within the ALC are associated with outcome of BCMA targeting bsAb therapy. Methods: We retrospectively collected data on 79 patients who had been treated with at least one full dose of a BCMA targeting bsAb. T cell subsets, including ALC, total CD3, CD4 and CD8, were measured from peripheral blood within 7 days prior to bsAb therapy initiation. Statistical analysis was performed with SAS version 9.4 using univariate and multivariate logistic regression models. Results: Median age of the patient cohort was 72 (31-84) years with 40/79 (51%) being male and 15/79 (19%) being African American. Median lines of therapy was 5 (2-12) with 78/79 (99%) patients being triple class refractory and 50/79 (63%) being penta-drug refractory. 59/79 (75%) of patients had at least one prior stem cell transplant (SCT) with 35/79 (44%) having had at least two SCTs. 26/79 (33%) patients had prior exposure to BCMA targeting therapy, with 18/79 (23%) and 8/79 (10%) previously having received belantamab mafodotin or BCMA targeting Car-T cell therapy respectively. Cytokine release syndrome (CRS) occurred in 38/79 (48%) of patients with the majority (92%) being grade 1 with the remainder being grade 2. Median ALC was 1.02 (0.25-5) x103/mL, median CD4 count was 0.27 (0.04-1.13) x103/mL while median CD8 count was 0.5 (0.07-2.97) x103/mL. Overall response (OR) rate of the whole cohort was 82% (69/79) with best responders (³very good partial response) comprising 51% (40/79). While total ALC, CD4 and CD8 counts did not appear to impact response to BCMA targeting bsAb therapy, the ratio of CD4 to ALC proved to be significantly associated with OR (univariate p=0.04) and best response (univariate p= 0.004, multivariate p=0.01) . The CD8 to ALC ratio had no significant impact in this patient population. The only other factor to show a significant association with response was the number of prior lines of therapy with higher numbers being associated with worse response (p=0.046). Conclusions: Our study suggests that an increased proportion of CD4 cells within the ALC is significantly associated with better response to BCMA targeting bsAb. While future studies are needed to elaborate on CD4 function in bsAB therapy, our findings imply that therapeutic strategies to increase the CD4 proportion could lead to improved bsAb therapy effectiveness.

Real-world outcomes of sacituzumab govitecan in breast cancer.

e13137 Background: Sacituzumab govitecan (Trodelvy), a novel antibody-drug conjugate, has emerged as a promising treatment option, in patients with metastatic triple-negative breast cancer (mTNBC). It gained FDA approval for unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies based on ASCENT trial which demonstrated that progression-free survival (PFS) and overall survival (OS) was significantly longer with sacituzumab govitecan than with single-agent chemotherapy. Hence, here in our current study, we further explore the outcomes of patients on sacituzumab govitecan in the setting of mTNBC. Methods: A single-center retrospective analysis was conducted on 21 women (aged 30-80 years old) with mTNBC breast cancer treated with sacituzumab govitecan over a span of 4 years. Baseline characteristics, pre-sacituzumab govitecan treatment PFS correlations, PFS and OS of sacituzumab govitecan were assessed and compared with the ASCENT trial. Results: A total of 21 women, comprising 10 African American, 10 Caucasian, and 1 Asian were evaluated over a span of 4 years. In our study with an average population of 50.6 years, the overall mean (± standard error of the mean) observed was 5.00 months (SEM 1.02) for PFS and 8.33 months (SEM 1.62) for OS. Patients with brain metastasis (n=8) and without brain metastasis (n=13) exhibited a mean of 5.99 months (SEM 2.23) and 4.40 months (SEM 0.97) for PFS respectively whereas 8.34 months (SEM 2.28) and 8.33 months (SEM 2.29) for OS respectively. The average number of previous treatment exposures in this subset was 5.6, with a mean PFS of 11.33 months (SEM 3.64) for prior treatment before initiation of sacituzumab govitecan. Conclusions: Our data reflects a similar interpretation with ASCENT trial study for mean PFS, however with a lower mean OS. In our study, the mean PFS from 8 patients who had brain metastasis closely matched with the patients without brain metastasis and the median PFS of the trial, thus suggesting potential consideration of sacituzumab govitecan in patients with active brain metastasis, as the patients with brain metastasis were excluded from the primary endpoint analysis in the ASCENT trial. No correlation was observed between the mean PFS of the prior line of therapy before sacituzumab govitecan and sacituzumab govitecan’s mean PFS. Overall, sacituzumab govitecan represents a significant advancement in breast cancer treatment and offers hope for patients with mTNBC.

Talquetamab (Tal) therapy in relapsed/refractory (R/R) multiple myeloma (MM): Assessing weight loss and dysgeusia.

e19514 Background: Tal, a bispecific antibody targeting CD3 and GPRC5D receptors, has shown high response rates in heavily pretreated R/R MM patients. This study aimed to evaluate adverse events (AEs), specifically dysgeusia and weight loss in MM patients treated with tal. Methods: Patients treated at the University of Arkansas for Medical Sciences who received at least one dose of tal were included. Common Terminology Criteria for Adverse Events (CTCAE) was used to grade AEs. The body mass index (BMI)-adjusted weight loss grading system (WLGS) was used to capture weight loss trends over duration of treatment. Weight loss based on BMI was graded based on the BMI-WLGS. Results: 17 patients were included in our analysis. Nine patients (53%) were male. Ten patients (59%) were African American. Median age at diagnosis was 62 (range: 51-75years). Six patients (35%) had Eastern Cooperative Oncology Group (ECOG) performance status ≥2. The median number of prior lines of therapy was seven (range: 3-12). Fourteen patients (82%) received at least one prior autologous hematopoietic stem cell transplant. The median number of tal doses received was 14.8 (range: 2-29). Median time on treatment (ranging from 1.15 to 15.84) was 4.36 months (range: 1.2-15.8 months). Overall response rate (ORR) for was 76%. Cytokine release syndrome occurred in 12 patients (70.6%), with 5 patients (29.4%) in grade 2 or higher CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) in four patients (23.6%), and 2 patients (11.8%) had grade 2 ICANS. Fourteen patients (82%) developed significant weight loss during treatment with tal. The median weight loss was 11.6 lbs., and median decrease in BMI was 1.85. Median percentage of weight loss was 6.1% from weight prior to tal ranging from 0% to 14.3%. Two patients had grade I, five patients had grade II, six patients had grade III, and one patient had grade IV weight loss per the BMI-WLGS grading system. Fourteen patients (82%) reported dysgeusia during tal treatment. Eight of these patients had grade I dysgeusia, and six patients had grade II dysgeusia. Two patients had persistent dysgeusia even after discontinuation of tal treatment at time of last follow up. Eight patients had weight gain after tal discontinuation (n = 8/14, 57%), with 5 returning to their baseline weight or higher. Six of these patients had dysgeusia during tal, and all six had resolution of dysgeusia after tal discontinuation. Conclusions: In this study, tal resulted in weight loss and dysgeusia in the majority of patients with most cases of dysgeusia resolving after tal discontinuation. Patients, on average, lost 6% of their initial weight during tal treatment. More than two-thirds of patients treated with tal developed BMI-adjusted WLGS grade ≥II. Weight loss persisted in approximately half of the patients after discontinuation of tal. Such AEs need to be discussed with patients and monitored during treatment.

Enhancing the patient journey to clinical trial enrollment with navigation to optimize accrual: A pilot study for a pragmatic multicentre, stepped wedge, cluster randomized controlled trial (The CTN Pilot Trial).

11093 Background: Clinical trials are essential to the advancement of clinical therapies, yet accrual rates remain disappointing. Multiple challenges lead to less than 5% of cancer patients enrolled onto clinical trials. The Clinical Trials Navigator (CTN) program was established to assist patients and health care professionals identify appropriate clinical trials for patients. Methods: Between March 2019 to January 2024, a novel navigator-assisted clinical trials search program was offered to Canadian patients. Three non-medical navigators were trained to receive referrals, review medical information, and search five different clinical trial search engines. Eligibility criteria was scrutinized. A second review of the clinical trial list was conducted by two physicians. The final curated list of clinical trials was provided to patients and their oncologist. Results: A total of 373 patients were referred to the CTN program during the study period. A unique clinical trial search was performed for each patient yielding a median of only one potentially eligible trial per patient. Clinical trial enrolment occurred in 3.2% of patients in our database which translates to a 19% rate of successful enrolment of those referred to a trial by the CTN. Most patients (78%) were referred to clinical trial sites that conducted more than 100 clinical trials at any time. Compared to the Canadian cancer statistics, lung, lymphoma, pancreatic and brain cancers were overrepresented in referrals to the CTN program while prostate cancer was underrepresented. Type of cancer played a significant role in the likelihood of a successful referral (p < 0.01). Lung cancer was the most frequently reported cancer that resulted in referrals and breast cancer showed a lower frequency of referrals. The cancer type, stage and number of lines of prior therapy were not significantly associated with the patient enrollment onto a clinical trial. An increase in survival of referred patients from last analysis from 3.0 months to 5.3 months. Conclusions: The CTN program is a successful tool to identify clinical trials for cancer patients and can improve clinical trial accrual, as almost one fifth of patients (19%) who were referred to a clinical trial were enrolled. Ongoing iterative changes to the program to improve these metrics are underway and efforts to improve implementation of the CTN program across Canada are ongoing.

Real-world outcomes of teclistamab for the treatment of relapsed/refractory multiple myeloma at UC San Diego Health: A single-institution experience.

e19504 Background: Bispecific antibodies (BsAb) are emerging as a promising class of cancer immunotherapy. Teclistamab, a BsAb targeting B-cell maturation antigen (BCMA) expressed on plasma cells, received FDA approval for the treatment of relapsed/refractory (R/R) multiple myeloma (MM) in 2022. Here we describe the real-world experience of teclistamab at a single institution. Methods: We retrospectively reviewed patients with R/R MM who received teclistamab at University of California San Diego and had at least 6 months of follow up. Baseline characteristics, efficacy outcomes, and safety outcomes were collected. Kaplan-Meier method was used to describe survival. Results: A total of 18 patients who received teclistamab between 01/01/2023 and 06/15/2023 were included in this analysis. The median age was 67 years old (range 50-83). Median prior lines of therapy was 6.5 (range 3-11). All patients had triple-refractory disease; all but one had penta-refractory disease. Approximately 44% of patients had extramedullary plasmacytomas at time of BsAb initiation; 39% had received prior BCMA therapy (2 belantamab, 5 ide-cel) before teclistamab. High-risk cytogenetics (t(4;14), t(14;16), t(14;20), Del17p, Gain1q) were characterized for 13 patients with data available. 6 had a single high-risk mutation, 4 had two, and 1 had three. Incidence of cytokine release syndrome (CRS) was 12 (67%); (4 (33%) grade 2, no grade 3-5). 6 (50%) received tocilizumab to treat CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) incidence was 2 (11%); (1 (50%) grade 2, no grade 3-5). Pain crisis occurred in 11% of patients. The incidence of infection was 67%; the majority were grade ≥ 3. The overall response rate (ORR) by IMWG criteria was 50%. All patients who responded had a very good partial response (VGPR) or better; further response data was not available due to the lack of restaging bone marrow biopsies during treatment. Median duration of response for the entire cohort was not reached. Median progression-free survival (PFS) was 12.5 months (95% CI 1.0 – not reached); median overall survival (OS) was not reached (95% CI 7.8 – not reached).Univariate analyses showed no statistically significant relationship between response and prior BCMA therapy (p=.91), response and presence of extramedullary disease (p=.31), or response and mSMART risk stratification (p=.13). Conclusions: Overall, the incidence and grades of CRS, ICANS, and infection in our cohort were similar to those observed in the phase I/II MajesTEC-1 trial. In contrast, the ORR and PFS in this study were lower compared to the MajesTEC-1 study. This difference may be due to a greater proportion of patients with high-risk cytogenetics and more aggressive disease, as depicted by the higher median prior lines of therapy and higher rates of extra-medullary plasmacytomas and triple-/penta-class refractory disease.