13MO - Safety and efficacy of tusamitamab ravtansine in combination with pembrolizumab ± chemotherapy in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05 phase II study)

Background

Pembrolizumab (pembro) ± chemotherapy is currently standard-of-care (SoC) first-line treatment for advanced/metastatic nonsquamous (NSQ) non-small cell lung cancer (NSCLC) without EGFR, BRAF or ALK/ROS aberrations. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression is often higher in cancerous vs healthy lung cells. Tusamitamab ravtansine (tusa rav) is a humanized CEACAM5-specific antibody-drug conjugate linked to DM4. Tusa rav monotherapy has shown encouraging antitumor activity and safety in patients with heavily pretreated CEACAM5-positive NSQ NSCLC.

Methods

CARMEN-LC05 assessed safety and antitumor activity of tusa rav in combination with SoC regimens: with pembro [T2]; with pembro + platinum-based chemotherapy (pCT) [T3]; and with pembro + pCT + pemetrexed [T4] in patients with advanced/metastatic NSQ NSCLC with CEACAM5 intensity of ≥2+ in ≥1% of tumor cells by immunohistochemistry. Tusa rav was given IV Q3W at 150 or 170 mg/m² in each treatment arm.

Results

As of Nov 28, 2022, 25 patients were treated for a median of 21 weeks (range 3–86); 12 (48%) were still on treatment. Dose-limiting toxicity of increased aspartate aminotransferase occurred in 1 patient in the T4 tusa rav 170 mg/m² group. The most frequent treatment-emergent adverse events (TEAE) were nausea (44%), diarrhea (36%), and asthenia (32%); Grade ≥3 events occurred in 68%; and Grade 5 events in 16% in the treatment period (all unrelated to tusa rav). Corneal TEAEs of any grade occurred in 24% of patients; but only 1 (keratitis) was Grade ≥3 in the T2 tusa rav 170 mg/m² group. Objective response rate (ORR) and disease control rate (DCR) for all patients were 40% and 88%, respectively.

Conclusions

Tusa rav combined with SoC showed encouraging antitumor activity across all treatment arms with a favorable safety profile, including in the T4 arm, and no new safety concerns, supporting ongoing evaluation of tusa rav.

Clinical trial identification

NCT04524689.

Editorial acknowledgement

Medical writing assistance was provided by Julian Martins, MA, MBBS, and Michael Stillman, PhD, inScience Communications, Springer Healthcare (Paris, France and New York, NY, respectively) and was funded by Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

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. 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. J.L. Gonzalez-Larriba: Financial Interests, Personal, Full or part-time Employment: Ministry of Universities, Spanish National Health System; Financial Interests, Personal, Advisory Board: Janssen-Cilag, MSD Oncology, Bristol-Myers Squibb, Boehringer Ingelheim; Financial Interests, Personal, 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, Other, Honoraria: MSD Oncology, Pfizer, Astellas Pharma, Roche, Novartis, Janssen-Cilag, Bristol-Myers-Squibb, AstraZeneca; Financial Interests, Personal, Speaker's Bureau: MSD Oncology. 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. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AstraZeneca, Eli Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, 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, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President. ASEICA (Spanish Association of Cancer Research): ASEICA; Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group. S. Shamai: Financial Interests, Personal, Full or part-time Employment: Sanofi. S. Bensfia: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. C. Soufflet: Financial Interests, Personal, Full or part-time Employment: Sanofi. A. Chevance: Financial Interests, Personal, Full or part-time Employment: Sanofi. R. Veillon: Financial Interests, Personal, Research Grant: Roche, Takeda, AbbVie, Merck; Financial Interests, Personal, Speaker's Bureau: MSD, BMS, Takeda, AstraZeneca, Janssen. All other authors have declared no conflicts of interest.