1311P - Phase II, open-label study of frontline tusamitamab ravtansine with pembrolizumab ± chemotherapy in advanced non-squamous non-small cell lung cancer: Updated results from CARMEN-LC05 trial

Background

CARMEN-LC05 (NCT04524689), a Phase 2, open-label, non-randomised study, evaluated tusamitamab ravtansine (tusa rav), a CEACAM5-targeting antibody-drug conjugate, in combination with pembrolizumab (pembro) and pembro + platinum-based chemotherapy (pCT) ± pemetrexed in patients (pts) with CEACAM5⁺ non-squamous non–small-cell lung cancer (NSQ NSCLC). Here, we present updated safety and efficacy data from CARMEN-LC05.

Methods

Tusa rav was assessed in combination with standard-of-care (SoC) therapies via two approaches: with pembro (substitution approach); with pembro + pCT; and with pembro + pCT and pemetrexed (add-on approaches) in advanced NSQ NSCLC with CEACAM5 intensity of ≥ 2+ in ≥ 1% of cells. Tusa rav was given (intravenous, every 3 weeks) at 150 or 170 mg/m² in each treatment arm. Primary endpoints were dose-limiting toxicity at Cycle 1 and objective response rate (ORR; confirmed partial response or complete response) per RECIST v1.1. For the secondary endpoints of PFS and DOR, median with two-sided 95% CI were estimated using the Kaplan–Meier method.

Results

As of March 21, 2024, 57 pts were treated with tusa rav for a median of 27.3 weeks (range 3.0; 128.9). All pts had treatment-emergent adverse events, of which 21 (36.8%) had any serious adverse events. Corneal events and peripheral neuropathies were reported in 20 (35.1%; Grade ≥ 3: 1 [1.8%]) and 23 (40.4%; Grade ≥ 3: 5 [8.8%]) pts, respectively. Deaths were reported in 16 (28.1%) pts due to disease progression (8 [14.0%]) pts, adverse events (6 [10.5%]) or others (2 [3.5%]). OR was observed in 30 (52.6%) pts with a median PFS of 11.6 months (95% CI 7.7; 15.9) and median DOR of 12.4 months (95% CI 8.4; 24.1) at cut-off date.

Conclusions

Tusa rav in combination with pembro ± chemotherapy demonstrated encouraging antitumor activity across PD-L1 subgroups and was associated with a favourable safety profile.

Table: 1311P

1311P Safety and efficacy

Clinical trial identification

NCT04524689.

Editorial acknowledgement

Medical writing support for this abstract was provided by Himanshi Bhatia, PhD, of Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

D. Rodriguez Abreu: Financial Interests, Personal, Advisory Board: BMS, MSD, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly; Financial Interests, Personal, Other, Honoraria: BMS, MSD, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: BMS, MSD, Roche, Novartis. R. Veillon: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Merck-Serono, Bristol Myers Squibb, GSK, Novartis, Janssen, Gilead, Sanofi, Roche, Takeda, AbbVie; Financial Interests, Personal and Institutional, Speaker’s Bureau: MSD, BMS, Takeda, AstraZeneca, Janssen. M. Ravoire: Financial Interests, Personal and Institutional, Research Grant: Roche, AstraZeneca, Merck-Serono, Bristol Myers Squibb, Janssen, Gilead, Sanofi. J.L. Gonzalez-Larriba: Financial Interests, Personal and Institutional, Full or part-time Employment: Ministry of Universities, Spanish National Health System; Financial Interests, Personal and Institutional, Advisory Board: Janssen-Cilag, MSD Oncology, Bristol Myers Squibb, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Grant: Miratti Therapeutics, AstraZeneca, Bayer, OncoMed, Astellas Pharma, Janssen-Cilag, Roche, AbbVie, Boehringer Ingelheim, Pfizer, PharmaMar, Bristol-Myers-Squibb, Novartis, Celgene, Ignyta; Financial Interests, Personal and Institutional, Other, Honoraria: MSD Oncology, Pfizer, Astellas Pharma, Roche, Novartis, Janssen-Cilag, Bristol-Myers-Squibb, AstraZeneca; Financial Interests, Personal and Institutional, Speaker’s Bureau: MSD Oncology. F.J. Orlandi: Financial Interests, Institutional, Research Grant: AbbVie, Amgen, Astellas Pharma, AztraZeneca, BMS, Celltrion, Daiichi Sankyo, GSK, MSD, PharmaMar, Pfizer, Sanofi; Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, MSD, Pfizer, Roche, Takeda; Financial Interests, Institutional, Speaker’s Bureau: AstraZeneca, MSD, Pfizer. L.G. Paz-Ares: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Roche, MSD, BMS, AstraZeneca, Eli Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal and Institutional, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal and Institutional, Other, Board Member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Eli Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Membership or affiliation: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President: ASEICA; Financial Interests, Personal, Other, Foundation President: ONCOSUR; Financial Interests, Personal, Other, Member: Small Lung Cancer Group. C.H. Huang: Non-Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals; Financial Interests, Personal, Other, Self/Spouse: Vanguard Health Care Mutual Fund; Financial Interests, Institutional, Research Grant: Sanofi, Amgen, Novartis, Pfizer, Incyte, Genentech, Exelixis, Nektar, EpicentrRx. N. Isambert: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Other, Honoraria: BMS, Amgen, Daiichi Sankyo; Financial Interests, Personal, Other: Pfizer, Roche, PharmaMar, Novartis. M.R. García Campelo: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche/Genentech, MSD Oncology, AstraZeneca, Bristol Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, Janssen Oncology; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Bristol Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, MSD Oncology, Sanofi/Aventis, Janssen Oncology, Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche/Genentech, MSD Oncology, Pfizer. A. Onn: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche Israel, MSD Israel, Boehringer Ingelheim, and AstraZeneca. L. Charbonnier, C. Soufflet: Financial Interests, Personal, Full or part-time Employment: Sanofi. All other authors have declared no conflicts of interest.