The Phase III CARMEN-LC03 trial, which investigated the efficacy of tusamitamab ravtansine, a CEACAM5-directed antibody-drug conjugate, versus docetaxel in previously treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC), did not meet its dual primary endpoints of progression-free survival and overall survival. The findings, presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer by Benjamin Besse, MD, PhD, of Gustave Roussy, led to the study's termination in December 2023.
Study Details and Patient Population
The CARMEN-LC03 trial enrolled 389 patients with advanced nonsquamous NSCLC who had previously undergone platinum-based chemotherapy and immunotherapy. Participants were randomized (1:1) to receive either tusamitamab ravtansine (100 mg/m2 every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks). Inclusion criteria included high CEACAM5 expression, defined as ≥2+ intensity in ≥50% of tumor cells, assessed by immunohistochemistry. The data cutoff date was September 22, 2023.
Primary and Secondary Endpoints
The dual primary endpoints were independent review committee-assessed progression-free survival and overall survival. Key secondary endpoints included objective response rate, health-related quality of life, duration of response, and safety. The median follow-up was 7.4 months for progression-free survival and 18.1 months for overall survival.
Efficacy Outcomes
The median progression-free survival was 5.4 months with tusamitamab ravtansine and 5.9 months with docetaxel (HR=1.14, 95% CI=0.86–1.51; P=0.8204). The median overall survival was 12.8 months and 11.5 months, respectively (HR=0.85, 95% CI=0.64–1.11; P=0.112). Subgroup analyses suggested a trend toward improved progression-free and overall survival with tusamitamab ravtansine in patients with CEACAM5 expression levels of at least 80%.
Safety Profile
The incidence of treatment-related adverse events of grade 3 or higher was lower with tusamitamab ravtansine (14.9%) compared to docetaxel (39.5%). Serious treatment-related adverse events (6.2% vs 20.3%) and treatment-emergent adverse events leading to treatment discontinuation (7.7% vs 16.9%) and dose reduction (16.5% vs 36.2%) were also less frequent with tusamitamab ravtansine. However, dose delay was more frequently required with tusamitamab ravtansine (42.8% vs 28.2%). Ocular adverse events, including corneal events, were consistent with previous studies of tusamitamab ravtansine.
Expert Commentary
Saiama N. Waqar, MD, MSCI, of the Washington University School of Medicine, commented on the trial, noting that docetaxel has been a standard of care in the second-line setting for over 20 years. While tusamitamab ravtansine did not meet its primary endpoints, Dr. Waqar highlighted the need for further refinement of biomarker cutoffs, particularly regarding CEACAM5 expression. She also acknowledged a potential prognostic role for CEACAM5 in the CARMEN-LC03 study, based on exploratory analyses.
