Abstract 75TiP
Background
Pembrolizumab +/− chemotherapy (CT) is the current, standard first-line (1L) treatment for advanced/metastatic nonsquamous (NSQ) non-small cell lung cancer (NSCLC) with no EGFR/ALK alterations. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is surface expressed on some tumors, including NSCLC. Tusamitamab ravtansine (tusa), an anti-CEACAM5 mAb conjugated with the potent cytotoxic maytansinoid antitubulin agent DM4, has shown encouraging single-agent results in patients (pts) with heavily pretreated CEACAM5+ NSQ NSCLC; a phase 3 monotherapy study is ongoing in pts with prior CT and immune checkpoint inhibitors. Combinations of tusa and pembrolizumab may improve 1L outcomes without additional toxicity.
Trial design
CARMEN-LC05 aims to assess, in pts with CEACAM5+ NSCLC, the safety and antitumor activity of tusa in combination with pembrolizumab (Part A); with pembrolizumab + platinum-based CT (Part B); and with pembrolizumab + platinum-based CT + pemetrexed (Part C). Pts with NSCLC with high CEACAM5 expression (immunohistochemistry intensity ≥2+ in ≥50% of tumor cells) are assigned to Part A, B, or C based on investigator’s choice; moderate expressors (≥2+ in 1% to <50%) to Part C. Pts are ≥18 years old with advanced/metastatic NSQ NSCLC with no EGFR, BRAF, or ALK/ROS aberrations; no prior CT for treatment of advanced/metastatic disease; biopsy amenable disease; and ECOG PS 0–1. Key exclusion criteria are unresolved corneal disorders; concurrent anticancer or immunosuppressive therapies; past therapy targeting CEACAM5, PD-L1, CD137, or CTLA-4; or treatment with maytansinoids. A safety run-in for Parts A, B, and C will assess the dose-limiting toxicities for each part and determine the recommended dose when combined with the other therapies. The primary objective is to assess tolerability and determine the recommended dose in the combinations in Parts A, B, and C. Key secondary objectives are safety/tolerability, antitumor activity (objective response rate), pharmacokinetics, and immunogenicity. As of Jan 5, 2022, 27 sites in 7 countries are recruiting.
Clinical trial identification
NCT04524689.
Editorial acknowledgement
Medical writing assistance was provided by Chase Pectol, PhD, and Elizabeth Strickland, PhD, inScience Communications, Springer Healthcare (Philadelphia, PA).
Legal entity responsible for the study
Sanofi, Inc.
Funding
Sanofi, Inc.
Disclosure
L. Paz-Ares: Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Blueprint; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Mirati; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Advisory Board, Spouse: AAA; Financial Interests, Personal, Other, Honoraria; Spouse: AAA; Financial Interests, Personal, Advisory Board: Advanz Pharma; Financial Interests, Personal, Other, Honoraria; Spouse: Advanz Pharma; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Other, Honoraria; Spouse: Bayer; Financial Interests, Personal, Advisory Board: HMP; Financial Interests, Personal, Other, Honoraria; Spouse: HMP; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Other, Honoraria; Spouse: Ipsen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Other, Honoraria; Spouse: Merck; Financial Interests, Personal, Advisory Board: Midatech Pharma; Financial Interests, Personal, Other, Honoraria; Spouse: Midatech Pharma; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Honoraria; Spouse: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Honoraria; Spouse: Novartis; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Other, Honoraria; Spouse: PharmaMar; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Other, Honoraria; Spouse: Pfizer; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Other, Honoraria; Spouse: Pierre Fabre; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Other, Honoraria; Spouse: Servier; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Other, Honoraria; Spouse: Sanofi; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Roche. S. Parakh: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD. C. Rojas: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Knight. F. Orlandi: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Celltrion; Financial Interests, Personal, Research Grant: Exelixis; Financial Interests, Personal, Research Grant: MabXience; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche. R. Veillon: Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Takeda; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Janssen. N. Isambert: Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Daiichi; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Other: Roche; Financial Interests, Personal, Other, Other: PharmaMar; Financial Interests, Personal, Other, Other: Novartis. D. Rodriguez-Abreu: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Lilly. A. Puaud: 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. N. Yang: Financial Interests, Personal, Full or part-time Employment: Sanofi. A. Spira: Financial Interests, Personal, Full or part-time Employment: Virginia Cancer Specialists; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Mirati Therapeutics; Financial Interests, Personal, Advisory Board: Gritstone Oncology; Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Janssen Research & Development; Financial Interests, Personal, Research Grant: LAM Therapeutics; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics; Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Janssen Oncology; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Institutional, Advisory Board: Array BioPharma; Financial Interests, Institutional, Advisory Board: AstraZeneca/MedImmune; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Boegringer Ingelheim; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: MedImmune; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Newlink Genetics; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Ignyta; Financial Interests, Institutional, Research Grant: LAM Therapeutics; Financial Interests, Institutional, Research Grant: Trovagene; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: CytomX Therapeutics; Financial Interests, Institutional, Research Grant: Astex Pharmaceuticals; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Loxo; Financial Interests, Institutional, Research Grant: Arch Therapeutics; Financial Interests, Institutional, Research Grant: Gritstone; Financial Interests, Institutional, Research Grant: Plexxikon; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: ADCT; Financial Interests, Institutional, Research Grant: Janssen Oncology; Financial Interests, Institutional, Research Grant: Mirati Therapeutics; Financial Interests, Institutional, Research Grant: Rubius. All other authors have declared no conflicts of interest.