Tusamitamab Ravtansine-Based Combinations Show Activity in NSCLC

Combination regimens including tusamitamab ravtansine have demonstrated activity in patients with CEACAM5-positive non-small cell lung cancer (NSCLC), according to a study presented at the European Lung Cancer Congress 2023.

In this phase 2 trial, responses were observed in patients who received tusamitamab ravtansine in combination with pembrolizumab alone, pembrolizumab plus platinum chemotherapy, or pembrolizumab plus platinum chemotherapy and pemetrexed. 

The trial (CARMEN-LC05; ClinicalTrials.gov Identifier: NCT04524689) enrolled 25 adults with advanced or metastatic nonsquamous NSCLC who were CEACAM5-positive by immunohistochemistry. The patients’ median age was 65 (range, 38-83) years, 48% of patients were women, 64% had high CEACAM5 expression (≥50%), and 12% had PD-L1 expression below 1%.

The patients were assigned to 1 of 3 treatment arms:

• In the T2 cohort, patients received tusamitamab ravtansine at 150 mg/m² or 170 mg/m² every 3 weeks as well as pembrolizumab every 3 weeks (n=5) 
• In the T3 cohort, patients received tusamitamab ravtansine and pembrolizumab at the same dosing schedule in combination with either cisplatin or carboplatin (n=5)
• In the T4 cohort, patients received tusamitamab ravtansine, pembrolizumab, platinum chemotherapy, and pemetrexed (n=15). 

At the data cutoff, 11 patients (44%) were still on study treatment. The median treatment duration was 24 weeks, and 7 patients were treated for at least 12 months.

Safety Results

The primary endpoint was dose-limiting toxicity. There was 1 dose-limiting toxicity (increased aspartate aminotransferase) in a patient from the T4 cohort who received tusamitamab ravtansine at 170 mg/m².

All patients experienced at least 1 treatment-emergent adverse event (TEAE). Grade 3 or higher TEAEs occurred in 68% of patients. The most common TEAEs were nausea (44%), diarrhea (36%), and asthenia (32%). Any-grade pneumonitis/interstitial lung disease (ILD) was reported in 16% of patients, and 4% of patients had grade 3 pneumonitis/ILD. 

There were 4 fatal TEAEs (16%). All of these patients were in the T4 cohort and received tusamitamab ravtansine at 150 mg/m².

Efficacy Results

In the entire cohort, the overall response rate was 52%, and the disease control rate was 88%. All 13 responses were partial responses, and 9 patients had stable disease.

In the T2 cohort, all 3 patients who received tusamitamab ravtansine at 150 mg/m² had a partial response. Both patients who received tusamitamab ravtansine at 170 mg/m² had stable disease.

In the T3 cohort, 2 of 4 patients who received tusamitamab ravtansine at 150 mg/m² had a partial response, and 2 had stable disease. The patient who received tusamitamab ravtansine at 170 mg/m² had stable disease. 

In the T4 cohort, 6 of 12 patients who received tusamitamab ravtansine at 150 mg/m² had a partial response, and 3 had stable disease. Two of 3 patients who received tusamitamab ravtansine at 170 mg/m² had a partial response, and 1 had stable disease.

Disclosures: This research was supported by Sanofi. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Paz-Ares L, Isambert N, Nagy T, et al.  Safety and efficacy of tusamitamab ravtansine in combination with pembrolizumab ± chemotherapy in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05 phase 2 study). ELCC 2023. March 29 – April 1, 2023. Abstract 13MO.