Tusamitamab Ravtansine Fails to Meet Survival Endpoints in NSCLC Trial

Tusamitamab ravtansine查看药品详情, an antibody-drug conjugate (ADC) targeting CEACAM5 (搜索)搜索该靶点, failed to significantly improve progression-free survival (PFS) or overall survival (OS) compared to docetaxel查看药品详情 in patients with advanced nonsquamous non-small cell lung cancer (NSCLC (搜索)搜索该疾病) expressing CEACAM5. These findings were presented from the phase 3 CARMEN-LC03 trial (NCT04154956查看临床试验) 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查看药品详情 arm (n = 194) and 5.9 months (95% CI, 5.5-7.4) in the docetaxel查看药品详情 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查看药品详情 at 100 mg/m2 every 2 weeks or docetaxel查看药品详情 at 75 mg/m2 every 3 weeks. Key eligibility criteria included patients with nonsquamous NSCLC (搜索)搜索该疾病 previously treated with platinum-based chemotherapy and an immune checkpoint inhibitor (ICI), CEACAM5 (搜索)搜索该靶点 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 (搜索)搜索该靶点 expression favored tusamitamab ravtansine查看药品详情 over docetaxel查看药品详情 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查看药品详情, with fewer grade 3 or higher or serious adverse events (AEs) and treatment discontinuations compared to docetaxel查看药品详情. 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查看药品详情.