Tusamitamab Ravtansine Fails to Prolong Survival in Nonsquamous NSCLC

On Friday, September 13, 2024, a study presented at the International Association for the Study of Lung Cancer's 2024 World Conference on Lung Cancer in San Diego revealed that Tusamitamab ravtansine (tusa rav), an immunoconjugate, does not enhance progression-free survival (PFS) in patients with previously treated advanced nonsquamous non-small cell lung cancer (NSCLC). The study was conducted by Benjamin Besse from Gustave Roussy in Paris and his colleagues.

The CARMEN-LC03 trial involved adult participants with advanced nonsquamous NSCLC who had previously undergone platinum-based chemotherapy and immunotherapy. These participants were randomly assigned to receive either tusa rav at a dose of 100 mg/m² every two weeks (194 patients) or docetaxel at a dose of 75 mg/m² every three weeks (177 patients). The study focused on comparing survival rates among patients whose tumors exhibited CEACAM5 positivity, as determined by immunohistochemistry, with an intensity of ≥2+ in at least 50 percent of tumor cells.

During the trial, the researchers monitored the patients for a median duration of 7.4 months for PFS, as assessed by an independent radiologic committee, and 18.1 months for overall survival (OS). The results indicated that the median PFS for patients receiving tusa rav was 5.4 months compared to 5.9 months for those receiving docetaxel. The hazard ratio (HR) was 1.14 with a 95 percent confidence interval (CI) ranging from 0.86 to 1.51, and the P-value was 0.820, indicating no significant difference in PFS between the two groups. Additionally, the median OS for tusa rav was 12.8 months versus 11.5 months for docetaxel, with an HR of 0.85 and a 95 percent CI of 0.64 to 1.11, and a P-value of 0.112.

Objective response rates were found to be similar between the two treatment groups. However, patients receiving tusa rav experienced a numerically prolonged time to the deterioration of disease-related symptoms, physical functioning, and role functioning. Importantly, tusa rav was associated with fewer grade ≥3 treatment-related adverse events (AEs) and serious AEs, which led to fewer treatment discontinuations and dose reductions compared to docetaxel. Nonetheless, dose delays were more frequent in the tusa rav group, primarily due to corneal events. The incidence and severity of ocular AEs in the tusa rav group were consistent with previous studies.

Despite some trends favoring tusa rav in interim OS and electronic patient-reported outcomes analysis, the study did not achieve its dual primary endpoint of improving PFS as assessed by central review. The researchers suggest that this outcome may be due to unexpectedly higher median PFS and OS observed with docetaxel.

In summary, the CARMEN-LC03 trial concluded that tusa rav does not provide a significant improvement in progression-free survival for patients with advanced nonsquamous NSCLC who have been previously treated with platinum-based chemotherapy and immunotherapy. While there were some favorable trends for tusa rav in terms of overall survival and patient-reported outcomes, the higher than anticipated effectiveness of docetaxel likely influenced the study's results.

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