1411P - Tusamitamab ravtansine plus ramucirumab as 2L therapy or beyond in patients with metastatic NSq NSCLC and high CEACAM5 expression (CARMEN-LC04)

Background

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression is often higher in malignant versus normal lung tissue. Tusamitamab ravtansine (tusa rav), an antibody-drug conjugate of humanized CEACAM5 antibody linked to cytotoxic DM4, showed promising antitumor activity and safety in heavily pretreated metastatic nonsquamous non-small cell lung cancer (mNSQ NSCLC) with high CEACAM5 expression. Docetaxel ± ramucirumab (ram) every 3 weeks is standard second-line therapy for mNSQ NSCLC without targetable mutations after progression on immunotherapy ± chemotherapy.

Methods

CARMEN-LC04 is an open-label phase 2 study (NCT04394624) assessing combination tusa rav 100 mg/m² every 2 weeks (Q2W) + ram 8 mg/kg Q2W in patients with mNSQ NSCLC and high CEACAM5 expression (≥2+ intensity in ≥50% of tumor cells by immunohistochemistry). Patients had progression after an immune checkpoint inhibitor + platinum-based chemotherapy; patients with EGFR or BRAF mutations or ALK/ROS alterations had progression on targeted therapy. Primary endpoints were dose-limiting toxicity (DLT) in the first 4 weeks for Part 1 and objective response rate (ORR: confirmed complete response [CR] or partial response [PR]) per RECIST v1.1 for Part 2. Safety, disease control rate (DCR: CR + PR + stable disease), and progression-free survival (PFS) were assessed.

Results

As of April 2023, 31 total patients were treated in Parts 1 and 2. The median duration of exposure was 24.1 weeks (range, 3.9–106.0), with 6 (19.4%) patients still on treatment. No DLTs were observed (DLT-evaluable patients, n = 6). ORR was 19.4% (6/31) with 1 CR; DCR was 83.9% (26/31). Target lesion shrinkage occurred in 23/31 (74.2%) patients. Median PFS was 5.7 months (95% confidence interval, 5.4–9.1). Treatment-emergent adverse events (TEAEs) occurred in all patients; 12 (38.7%) patients had a Grade ≥3 TEAE. Seven (22.6%) patients had ≥1 corneal TEAEs: 5 (16.1%) Grade 2 and 2 (6.5%) Grade 3 as worst Grade. No treatment-emergent interstitial lung disease or toxic death was reported.

Conclusions

Tusa rav + ram showed encouraging efficacy. The safety of this combination was consistent with the safety profile of each drug, with no unexpected safety signals.

Clinical trial identification

NCT04394624.

Editorial acknowledgement

Medical writing assistance was provided by Micaela Genca, PharmD, inScience Communications, Springer Healthcare (Philadelphia, PA).

Legal entity responsible for the study

Sanofi, Inc.

Funding

Sanofi, Inc.

Disclosure

B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus Therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J Ints Bio; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, BridgeBio Therapeutics, Kanaph Therapeutic Inc, Cyrus Therapeutics, Interpark Bio Convergence Corp., J Ints Bio; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, BridgeBio Therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Founder: Daan Biotherapeutics. J. Oliveira: Financial Interests, Personal, Other, Advisory board, Invited speaker: AstraZeneca, Roche, Novartis, Janssen; Financial Interests, Personal, Invited Speaker: GSK, BMS, MSD, Bayer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Funding, Investigator Initiated Clinical Trial funding: AstraZeneca. L. Vila Martinez: Financial Interests, Personal, Advisory Board: Roche Pharma SA, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Merck, Roche Pharma. L. Charbonnier: 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. J. de Castro Carpeño: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Merck Sharp and Dohme, Roche. All other authors have declared no conflicts of interest.