29P - Evaluation of tusamitamab ravtansine, a CEACAM5-targeting antibody drug conjugate, in non-squamous NSCLC participants with negative or moderate CEACAM5 expression and high circulating CEA: Results from phase II CARMEN-LC06 trial

Background

This phase II study evaluated efficacy and safety of tusamitamab ravtansine in non-squamous NSCLC participants with high baseline circulating carcinoembryonic antigen (cCEA; ≥100 ng/mL) and negative or moderate carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression on archival tumor tissue. CEACAM5 is elevated in cancers and shed as cCEA used to detect cancers, including lung cancer. It was hypothesized that participants with negative or moderate CEACAM5 expression from archival biopsy with high cCEA levels at study entry might have higher tumor CEACAM5 expressions at study entry.

Methods

Planned enrollment was 38 participants, but due to early study termination, 22 participants who failed pre-screening in the phase III CARMEN-LC03 study were enrolled. Four participants benefiting continued therapy. Participants received 100 mg/m² tusamitamab ravtansine intravenously every 2 weeks. The primary endpoint was objective response rate (ORR). Secondary endpoints were treatment emergent adverse events (TEAEs), progression-free survival (PFS), disease control rate (DCR), and duration of response (DOR).

Results

Baseline mean age: 63.5 years and mean BSA: 1.75 m². As of March 2024, ORR was 9.1% (95% CI: 1.1–29.2); 2 participants (9.1%) had partial responses, and 6 (27.3%) achieved stable disease per RECIST v1.1. Median PFS was 1.9 months (95% CI: 1.7–3.6) and DCR was 36.4% (95% CI: 17.2–59.3). Median number of treatment cycles per participant was 5 (range: 1–23). Safety overview is given in the table.

Overview of the safety profile

SAEs, serious AEs; TEAEs, treatment-emergent AEs; TRAEs, treatment-related AEs.

^aCommon TEAEs (≥15% participants): Decreased appetite (40.9%), asthenia, nausea (27.3% each), dyspnea (18.2%).

^bKeratopathy (3 participants, 13.6%) and keratitis (2 participants, 9.1%).

^cEye pain, maculopathy, eyelid swelling and xerophthalmia (1 participant each).

Conclusions

Modest antitumor efficacy was observed in some participants; however, the study was limited by low enrollment. No new safety signals were observed; safety was consistent with other clinical studies. Early termination was due to the sponsor’s decision to discontinue the clinical development of tusamitamab ravtansine.

Clinical trial identification

NCT05245071.

Editorial acknowledgement

Medical writing support for this abstract was provided by Ujara Shaikh of Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

H. Lena: Financial Interests, Personal, Advisory Board: Sanofi, Roche, Novartis, Daiichi Sankyo, Takeda, MSD; Other, Personal, Other, support for attending meetings or travel: Sanofi, Roche, Amgen, Takeda, Pfizer. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, AbbVie, Gilead, Regeneron; Financial Interests, Personal, Other, Board member: Altum sequencing; Financial Interests, Personal, Other, lectures: AICME; Financial Interests, Personal, Other, Lectures: CCO; Financial Interests, Personal, Expert Testimony: Boehringer; Financial Interests, Personal, Member of Board of Directors, spinn off (I have arounfd 8% of stocks): Altum sequencing; Financial Interests, Personal, Member of Board of Directors: Stab therapeutics; Financial Interests, Personal, Ownership Interest, spin-off (10%): Stab Therapeutics; Financial Interests, Personal, Stocks/Shares, co-founder: Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-cilag international NV, NOvartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar, Cantargia; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President: ASEICA (Spanish Association of Cancer Research); Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group; Non-Financial Interests, Personal, Other, Board member of this anti-cancer Charity: AECC; Non-Financial Interests, Personal, Member, Past-President: ASEICA (Spanish Cancer Research Association); Non-Financial Interests, Personal, Leadership Role, President: Oncosur Foundation. M. Ozguroglu: Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board, Advisory role: MSD; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. C. Helissey: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca, MSD, BMS, viatris, Accord, Bayer, Ipsen, GSK, ESAI; Financial Interests, Personal, Advisory Board: Macrogenics; Non-Financial Interests, Personal, Principal Investigator: Janssen, Sanofi, Roche, Astellas, Macrogenics, Regeneron, Gilead. G. Lo Russo: Financial Interests, Personal, Advisory Board: MSD, Novartis, AstraZeneca, BMS, Sanofi, Pfizer, Roche, Lilly, GSK, Daiichi, Johnson and Johnson, Regeneron, Merck, Pierre Fabre; Financial Interests, Personal, Invited Speaker: italfarmaco, Merck, BMS, Lilly, Sanofi; Financial Interests, Institutional, Other, contribute for meeting organization: Janssen; Financial Interests, Institutional, Other, contribute for meeting organization: Bayer; Financial Interests, Personal, Other, travel accommodation: Amgen, MSD; Financial Interests, Institutional, Other, Contribute to meeting organization: Beigene; Financial Interests, Institutional, Invited Speaker: MSD, BMS, Roche, GSK, Celgene, Novartis, AstraZeneca, Amgen, Lilly. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, Roche, PharmaMar. A. Martinez Bueno: Financial Interests, Personal, Invited Speaker: Seagen, GSK, AZ; Financial Interests, Personal, Other, Travel expenses, accommodation and registration fees: Roche, GSK; Financial Interests, Personal, Other, Travel expenses, accommodations and registration fees: MSD; Financial Interests, Institutional, Research Grant: GSK. M. Celanovic: Other, Personal, Full or part-time Employment, may hold stock and/or stock options: Sanofi. Y. Mekhloufi: Other, Personal, Full or part-time Employment, may hold stock and/or stock options: Sanofi. E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen, Regeneron, Pierre Fabre, Genmab, Apollomics; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi, Illumina; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche, Transgene; Other, Personal, Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP). All other authors have declared no conflicts of interest.