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.
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.
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.
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.
| Table of outcomes | T2 | T3 | T4 | All | |||
| Tusa rav dose, mg/m2 | 150 | 170 | 150 | 170 | 150 | 170 | |
| Number of patients | 3 | 2 | 4 | 1 | 12 | 3 | 25 |
| Any TEAE, n (%) | 3 (100) | 2 (100) | 4 (100) | 1 (100) | 12 (100) | 3 (100) | 25 (100) |
| Grade ≥3 TEAE, n (%) | 2 (66.7) | 2 (100) | 2 (50.0) | 1 (100) | 8 (66.7) | 2 (66.7) | 17 (68.0) |
| Grade 5 TEAE, n (%) | 0 | 0 | 0 | 0 | 4 (33.3) | 0 | 4 (16.0) |
| TEAE leading to permanent discontinuation, n (%) | 0 | 0 | 0 | 1 (100) | 3 (25.0) | 1 (33.3) | 5 (20.0) |
| Corneal TEAE, n (%) | 2 (66.7) | 1 (50.0) | 0 | 1 (100) | 1 (8.3) | 1 (33.3) | 6 (24.0) |
| ORR (confirmed complete response [CR] or partial response [PR]), n (%; 95% CI) | 3 (100) | 0 (0.0) | 2 (50.0) | 0 (0.0) | 3 (25.0) | 2 (66.7) | 10 (40.0; 21.1, 61.3) |
| DCR (confirmed CR, PR, or stable disease), n (%; 95% CI) | 3 (100) | 2 (100) | 4 (100) | 1 (100) | 9 (75.0) | 3 (100) | 22 (88.0; 68.8, 97.5) |
NCT04524689
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.