1801P - Expression analysis of Fuc-GM1 ganglioside in first-line therapy for extensive-stage small cell lung cancer (ES-SCLC) with BMS-986012, nivolumab, and carboplatin-etoposide

Background

The baseline expression of Fuc-GM1 was assessed in a phase II clinical trial (NCT04702880) that investigated the effect of adding BMS-986012, a novel monoclonal antibody targeting Fuc-GM1 and promoting immune-mediated tumor cell death, to nivolumab and chemotherapy (carboplatin + etoposide) in ES-SCLC. The study explored potential correlations between biomarker expression and clinical outcomes. In this study, 65 patients were treated in Arm A (receiving BMS-986012) and 64 in Arm B (the control group). Results on clinical efficacy will be detailed in a separate abstract.

Methods

As of March 2024, 37 baseline frozen tumor samples were analyzed by immunohistochemistry (IHC) and 69 tumor samples by liquid chromatography-mass spectrometry (LC/MS), with 100 plasma samples also analyzed for shed-Fuc-GM1 by LC/MS. Any detection above zero was considered positive. Median overall survival (mOS) was from pre-specified interim analysis data cut-off of August 28, 2023.

Results

Median Fuc-GM1 expression: 130 H-score (IHC), 78 pg/mg (LC/MS), with a correlation between the two methods (R=0.72). Positivity rates: 78% (29/37, IHC), 68% (47/69, LC/MS). Of 36 patients with data from both methods, 72% were positive when both methods agreed, and 92% were positive when at least one method indicated positivity. Positivity rates in arms A and B were comparable: IHC 76% (13/17) vs. 80% (16/20) (p=1.00), LC/MS 64% (21/33) vs. 72% (26/36) (p=0.60). In arm A, Fuc-GM1 expression showed no significant correlation with mOS (Table). Shed-Fuc-GM1 was detected in 52% (52/100) of plasma samples collected at C1D1 before dosing and showed a moderate correlation with tumor Fuc-GM1 expression, as determined by IHC (R=0.35) or LC/MS (R=0.35). Table: 1801P

Baseline Fuc-GM1 positivity in arm A stratified by mOS of 15.6m

Note: P-value determined by Fisher’s exact test

Conclusions

Fuc-GM1 is highly expressed in SCLC from this study but levels do not appear to correlate with the clinical activity of BMS-986012.

Clinical trial identification

NCT04702880.

Editorial acknowledgement

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

K.J. O'Byrne: Financial Interests, Personal, Other, Advisor/consultant on project development by the company: TriStar; Financial Interests, Personal, Other, Invited speaker; advisory board: BMS; Financial Interests, Personal, Other, Advisory board; invited speaker: AstraZeneca, MSD, Janssen; Financial Interests, Personal, Other, advisory board; invited speaker: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Other, Advisory board: Pfizer; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board, Advice on development of Lasertinib: Yuhan; Financial Interests, Personal, Other, advisory board and invited speaker: Takeda, seagen; Financial Interests, Personal, Advisory Board, Advice re cabozantinib: Ipsen; Financial Interests, Personal, Advisory Board, Advice of drug development program, advisory board work and invited speaker: Beigene; Financial Interests, Personal, Invited Speaker, Topic - Tepotinib: Merck; Financial Interests, Personal, Other, Sponsorship for travel, accommodation and registration for ESMO Congress, Paris, 2022: Bayer; Financial Interests, Personal, Other, Sponsorship to ESMO annual congress 2023 - flights, registration and accommodation: Sanofi; Financial Interests, Personal, Stocks/Shares, 5% non-dilutable shares in a start-up Pharma company: RepLuca Pharmaceuticals Pty Ltd; Financial Interests, Personal, Stocks/Shares, Start-up diagnostics focused on genomics: DGC diagnostics; Financial Interests, Personal, Other, Co-founder, board member and share holder (15%) in the Pharma and biotech company: Carpe Vitae Pharmaceuticals Pty Ltd; Financial Interests, Personal, Steering Committee Member, Steering committee member 2 trials- CA-209-227- CA-001-050: BMS; Financial Interests, Personal, Steering Committee Member, Steering Committee member LUX-Lung program: Boehringer Ingelheim; Non-Financial Interests, Other, Chair an education session: foundation medicine. Y. Zhang: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. J. Ouyang: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. W. Chou, C. Chou, T. Hollmann, J.A. Zeng, L. Corrella, M. Metzler, C. Green, E. Lees, Y. Liu, L. Ojalvo, B. Wu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Wu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. O. Adelakun: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb-Lawrenceville, NJ; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb-Lawrenceville, NJ; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb-Lawrenceville, NJ. R. Sarmiento: Financial Interests, Institutional, Full or part-time Employment, I am full time employee of BMS: BMS; Financial Interests, Institutional, Stocks/Shares, I own BMS shares: BMS.