by International Association for the Study of Lung Cancer

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Credit: Pixabay/CC0 Public Domain

A Phase III study comparing tusamitamab ravtansine with docetaxel in patients with advanced non-squamous non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and immunotherapy (in combination or sequential), whose tumors highly expressed CEACAM5, was presented at the International Association for the Study of Lung Cancer 2024 World Conference on Lung Cancer in San Diego, Calf., by Dr. Benjamin Besse of Gustave Roussy, in Paris, France.

As previously announced by Sanofi in December 2023, the study results did not meet its primary endpoint of improved progression-free survival (PFS).

Tusamitamab ravtansine is an immunoconjugate consisting of anti-carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) conjugated to a cytotoxic agent, with antineoplastic activity.

The CARMEN-LC03 is a Phase III open-label, randomized, pivotal, multicenter study evaluating tusamitamab ravtansine (a CEACAM5-directed antibody-drug conjugate (ADC) with cytotoxic payload DM4/ravtansine) versus docetaxel in patients with advanced non-squamous NSCLC previously treated with platinum-based chemotherapy and immunotherapy (in combination or sequential), whose tumors highly expressed CEACAM5.

Dr. Besse reported the results from the prespecified final progression-free survival and first interim overall survival (OS) analyses.

The trial randomized adult patients 1:1 to intravenously receive either 100 mg/ m2 tusamitamab ravtansine once every two weeks or docetaxel 75 mg/m2 once every three weeks.

Patients with CEACAM5 positivity (assessed by immunohistochemistry) of greater than or equal to 2+ intensity involving ≥50% of tumor cells were included in the study. CEACAM5 is a member of the CEACAM family of 12 glycoproteins and may drive cell adhesion and migration, as well as inhibit apoptosis, and may be overexpressed in many different cancer types.

Dual primary endpoints were PFS and OS. Secondary endpoints were objective response rate (ORR), health-related quality of life (HRQoL), duration of response and safety.

Besse and colleagues randomized 194 patients to receive tusamitamab ravtansine (all patients received treatment) and 195 to docetaxel of whom 177 received treatment; 61 patients (n=36 tusamitamab ravtansine and n=25 docetaxel) remained on treatment.

Most patients received one or two prior lines of therapy, had a median age of 64 years and the majority were males (59.6%). Median follow-up was 7.4 and 18.1 months for PFS (by Independent Radiologic Committee [IRC]) and OS, respectively.

According to data presented by Dr. Besse, results include:

  • Median progression-free survival as per IRC for tusamitamab ravtansine and docetaxel was 5.4 vs. 5.9 months, respectively (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 0.86-1.51; p=0.820).

  • Median overall survival (60% Information Fraction) of tusamitamab ravtansine vs. docetaxel was 12.8 vs. 11.5 months; HR=0.85 (95% CI [0.64-1.11]; p=0.112).

  • Similar overall response rate was observed with tusamitamab ravtansine and docetaxel. Time to deterioration of disease related symptoms/physical functioning/role functioning were numerically prolonged with tusamitamab ravtansine.

  • Grade ≥ 3 treatment-related adverse events and treatment-related serious AEs, TEAE leading to discontinuation and dose reduction were lower with tusamitamab ravtansine; however, dose delay was more frequently required for tusamitamab ravtansine, mainly due to corneal events.

"Despite trends favoring tusamitamab ravtansine on interim overall survival and electronic patient reported outcomes analysis, CARMEN did not meet its co-primary endpoint of improving PFS. The higher median PFS and OS observed with docetaxel was unexpected," said Dr. Besse. He noted that tusamitamab ravtansine showed better safety data in various important clinical categories.

These exploratory analyses identify patients with advanced non-squamous NSCLC previously treated with immunotherapy and chemotherapy who are likely to derive clinical benefit from CEACAM5-directed therapy and suggest a previously unknown prognostic role for CEACAM5 in NSCLC, Additional research would be needed to corroborate these findings.

Provided by International Association for the Study of Lung Cancer