Abstract 1364TiP
Background
In patients with metastatic non-small cell lung cancer (NSCLC) lacking targetable mutations who progress on immunotherapy and platinum-based chemotherapy, treatment options are generally limited to docetaxel ± a VEGF inhibitor such as ramucirumab. Surface expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) at higher levels in epithelial tumors than in normal tissues represents a novel target for anti-tumor agents. Tusamitamab ravtansine (tusa) is a humanized antibody to CEACAM5 conjugated with the potent cytotoxic maytansinoid derivative, DM4, an anti-tubulin agent. We report the design of CARMEN-LC04, evaluating safety and anti-tumor activity of tusa combined with ramucirumab in high CEACAM5-expressing non-squamous cell (NSQ) NSCLC tumors.
Trial design
Inclusion criteria include: ≥ 18 y/o; proven CEACAM5+ metastatic NSQ NSCLC, defined as CEACAM5 intensity ≥ 2+ in ≥ 50% of tumor cells by immunohistochemistry using a specific monoclonal anti-CEACAM5 antibody; progression after platinum-based chemotherapy and an immune checkpoint inhibitor; and in patients with EGFR or BRAF mutations or ALK/ROS alterations, progression on targeted therapy; and ≥ 1 measurable lesion by RECIST v1.1. Part 1 is a safety run-in phase with primary endpoints of dose-limiting toxicity (DLT) and determining the recommended phase II dose (RP2D) in a 3 + 3 design. Treatment with antihistamines precedes an intravenous (IV) infusion of ramucirumab, followed by an IV infusion of tusa, both in 2 weekly cycles. Part 2 primary endpoint is antitumor activity according to RECIST v1.1 in the response-evaluable population at tusa RP2D (30 patients anticipated). Parts 1 and 2 secondary endpoints include: safety, duration of response, progression-free survival, pharmacokinetics of tusa and ramucirumab, and anti-therapeutic antibodies. This study is recruiting participants at 12 sites in 6 countries, and has reached part 2 at all sites.
Clinical trial identification
NCT04394624.
Editorial acknowledgement
Editorial support was provided by Julian Martins, MBBS, MA, of inScience Communications (Philadelphia, PA, USA), funded by Sanofi.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
B.C. Cho: Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc.; Financial Interests, Personal, Stocks/Shares: Gencurix Inc.; Financial Interests, Personal, Stocks/Shares: BridgeBio Therapeutics; Financial Interests, Personal, Stocks/Shares: Kanaph Therapeutics Inc.; Financial Interests, Personal, Stocks/Shares: Cyrus Therapeutics; Financial Interests, Personal, Stocks/Shares: Interpark Bio Convergence Corp.; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Other, Consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Boehringer Ingelheim; Financial Interests, Personal, Other, Consultant: Roche; Financial Interests, Personal, Other, Consultant: BMS; Financial Interests, Personal, Other, Consultant: Ono; Financial Interests, Personal, Other, Consultant: Yuhan; Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Other, Consultant: Eli Lilly; Financial Interests, Personal, Other, Consultant: Janssen; Financial Interests, Personal, Other, Consultant: Takeda; Financial Interests, Personal, Other, Consultant: MSD; Financial Interests, Personal, Other, Consultant: Medpacto; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc.; Financial Interests, Personal, Advisory Board: BridgeBio Therapeutics; Financial Interests, Personal, Advisory Board: Cyrus Therapeutics; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Mogam Institute; Financial Interests, Personal, Research Grant: Dong-A ST; Financial Interests, Personal, Research Grant: Champions Oncology; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: Yuhan; Financial Interests, Personal, Research Grant: Ono; Financial Interests, Personal, Research Grant: Dizal Pharma; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Research Grant: Medpacto; Financial Interests, Personal, Research Grant: GI Innovation; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Blueprint Medicines; Financial Interests, Personal, Research Grant: Interpark Bio Convergence Corp.; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. C. Aguado de la Rosa: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: AstraZeneca. L. Vilà: Financial Interests, Personal, Advisory Role: Roche Pharma S.A.; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Roche Pharma. J. Oliveira: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Research Grant: AstraZeneca. J. de Castro Carpeno: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Jansen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme; Financial Interests, Personal, Speaker’s Bureau: Roche. T.M. Kim: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boryung; Financial Interests, Personal, Advisory Board: Hanmi; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Roche/Genentech; Financial Interests, Personal, Research Grant: AZ-KHIDI outside this work; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Blueprint Medicines; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Boryung; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Hanmi; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Merck KGaA; Financial Interests, Institutional, Research Grant: MEI Pharma; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: TP Therapeutics; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Yuhan; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Hanmi; Financial Interests, Personal, Other, Honoraria: Takeda. A. Bauchet: Financial Interests, Personal and Institutional, Full or part-time Employment: Sanofi; Financial Interests, Personal and Institutional, Stocks/Shares: Sanofi. C. Soufflet: Financial Interests, Personal, Full or part-time Employment: Excelya on behalf of Sanofi. S. Bensfia: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. All other authors have declared no conflicts of interest.