Tusamitamab ravtansine, an antibody-drug conjugate (ADC) targeting CEACAM5, failed to significantly improve progression-free survival (PFS) or overall survival (OS) compared to docetaxel in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) expressing CEACAM5. These findings were presented from the phase 3 CARMEN-LC03 trial (NCT04154956) at the IASLC 2024 World Conference on Lung Cancer.
In the intent-to-treat (ITT) population, the median PFS per independent review committee (IRC) was 5.4 months (95% CI, 3.7-7.0) in the tusamitamab ravtansine arm (n = 194) and 5.9 months (95% CI, 5.5-7.4) in the docetaxel arm (n = 195), with a hazard ratio of 1.14 (95% CI, 0.86-1.51; P = .8204). The median follow-up was 7.4 months. At a median follow-up of 18.1 months, the OS during the first interim analysis was 12.8 months (95% CI, 11.8-14.2) and 11.5 months (95% CI, 8.9-15.2) in the respective arms (HR, 0.85; 95% CI, 0.64-1.11; P = .112).
Trial Design and Patient Population
The phase 3, open-label, multicenter CARMEN-LC03 trial randomized 389 patients 1:1 to receive tusamitamab ravtansine at 100 mg/m2 every 2 weeks or docetaxel at 75 mg/m2 every 3 weeks. Key eligibility criteria included patients with nonsquamous NSCLC previously treated with platinum-based chemotherapy and an immune checkpoint inhibitor (ICI), CEACAM5 expression of at least 2+ intensity in at least 50% of tumor cells by immunohistochemistry (IHC), at least one measurable lesion per RECIST v1.1 criteria, and an ECOG performance status of 0 or 1. Patients were stratified by ECOG performance status, geographical region, and prior ICI treatment.
The dual primary endpoints were PFS per IRC and OS. Secondary endpoints included objective response rate (ORR), duration of response (DOR), safety, and health-related quality of life (HRQoL).
Subgroup Analysis and Quality of Life
Subgroup analysis indicated that patients with at least 80% CEACAM5 expression favored tusamitamab ravtansine over docetaxel for PFS (HR, 0.866; 95% CI, 0.597-1.257) and OS (HR, 0.711; 95% CI, 0.492-1.028). The time to deterioration in HRQoL in the ITT population showed a positive trend for tusamitamab ravtansine. The median survival for disease-related symptoms was 2.8 months (range, 2.1-4.3) and 1.9 months (range, 1.5-2.8) in the tusamitamab ravtansine and docetaxel arms, respectively. For role functioning, median survival was 5.6 months (range, 3.7-6.3) vs 4.2 months (range, 2.8-4.4) in the respective arms. The median survival for physical functioning was 7.5 months (range, 5.5-15.2) and 4.2 months (range, 3.0-4.6).
Safety Profile
The safety profile favored tusamitamab ravtansine, with fewer grade 3 or higher or serious adverse events (AEs) and treatment discontinuations compared to docetaxel. All-grade treatment-emergent AEs (TEAEs) occurred in 186 patients (95.9%) and 168 patients (94.9%) in the tusamitamab ravtansine and docetaxel arms, respectively; grade 3 or higher TEAEs occurred in 79 patients (40.7%) and 102 patients (57.6%). All-grade treatment-related AEs (TRAEs) occurred in 141 patients (72.7%) and 152 patients (85.9%) in the respective arms; 29 patients (14.9%) and 70 patients (39.5%) experienced grade 3 or higher TRAEs. TEAEs leading to dose reductions occurred in 32 patients (16.5%) and 64 patients (36.2%), while 15 patients (7.7%) and 30 patients (16.9%) experienced TEAEs leading to definitive treatment discontinuation.
According to Dr. Benjamin Besse, a medical oncologist and professor of medicine at Paris Saclay University, Institut Gustave Roussy, CARMEN-LC03 was discontinued in December 2023, but patients benefiting from treatment could continue to receive tusamitamab ravtansine.
