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

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. 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. 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. 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.