1106P - Capmatinib for METex14 non-small cell lung cancer patients: Results of the real-world study IFCT-2104 CapmATU

Background

MET exon 14 skipping (METex14) mutations are detected in 3% of non-small cell lung cancer (NSCLC) patients (pts). A recent clinical trial reported robust activity of capmatinib, a new generation MET tyrosine kinase inhibitor, in METex14 NSCLC. However, its efficacy and safety need to be confirmed in real-world (RW) setting.

Methods

We conducted a retrospective multicenter study including all NSCLC pts who received at least 1 dose of capmatinib as part of the French expanded access program in which capmatinib was given to pts who failed or were not eligible to standard treatments. Pts with MET aberrations different from METex14 mutations and those for whom METex14 was a mechanism of acquired resistance to other targeted therapies were excluded. The primary endpoint was time to treatment failure (TTF).

Results

160 pts received capmatinib and 146 had a METex14 NSCLC and were included in the analysis. Median age was 75 years. ECOG PS was 0, 1, ≥2 for 18 (16.2%), 56 (50.5%), 37 (33.3%) pts, respectively. Brain metastases were present in 47 pts (32.4%). Number of lines of treatment before capmatinib was 0, 1 or ≥2 for 23 (15.8%), 56 (38.4%) and 67 pts (45.9%). 46 (31.5%) pts received crizotinib before capmatinib. Median TTF was 5.1 months (m) [95% CI 4.2-6.0] and median PFS was 4.8 m [95% CI 4.0-6.0]. Best objective response rate (ORR) was 55.2% [95% CI 46.8-63.6]. For pts treated in 1^st, 2^nd and ≥3^rd line, median PFS was 7.7 m [95% CI 4.0-NR], 6.0 m [95% CI 3.6-7.7], 4.1 m [95% CI 2.5-5.1], respectively. Median PFS was 2.6 m [95% CI 2.1-4.6] for pts who received crizotinib before capmatinib, and 6.0 m [95% CI 4.5-7.7] for those who did not. PFS results were similar in PS 0-1 and in PS ≥2 pts. For pts with and without brain metastases, median PFS was 3.0 m [95% CI 2.4-5.8] and 5.3 m [95% CI 4.5-7.7]; best ORR was 47.6% [95% CI 32.5 - 62.7] and 58.7% [95% CI 48.6 - 68.8], respectively. Treatment discontinuation occurred in 118 pts and was due to toxicity in 18 (15.2%) pts, mostly because of edema (66.7%).

Conclusions

This RW study confirms effectiveness of capmatinib in METex14 NSCLC pts, including those who have been pretreated, with poor PS or brain metastases. These results highlight the need for early detection of METex14 mutations, given the availability of potent targeted therapies.

Clinical trial identification

NCT05154344.

Editorial acknowledgement

Legal entity responsible for the study

French Cooperative Thoracic Intergroup.

Funding

Novartis.

Disclosure

A. Swalduz: Financial Interests, Personal, Other, honoraria: AstraZeneca, Janssen, Roche, Amgen, BMS; Financial Interests, Personal, Advisory Role: AstraZeneca, Janssen, Roche, Amgen, BMS, Pfizer, Lilly. A.C. Toffart: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, BMS, Roche, Amgen, Takeda. J. Raimbourg: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS. V. Gounant: Financial Interests, Personal, Advisory Role: BMS, AstraZeneca, Takeda; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi, Pfizer. S. Couraud: Financial Interests, Personal, Other, honoraria: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Fabentech, Boehringer Ingelheim, Takeda; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Chugai, Novartis, Pfizer, Sysmex, Cellgene, Takeda, Janssen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Roche, Takeda. M. Wislez: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, Amgen, BMS, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, Amgen, BMS, Roche; Financial Interests, Institutional, Funding, research funding: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD, Amgen, BMS, Roche. V. Westeel: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BMS, Amgen, Roche; Financial Interests, Personal, Advisory Role: MSD, Takeda; Financial Interests, Personal, Speaker’s Bureau: BMS, AstraZeneca, Roche, MSD, Pfizer, Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS, AstraZeneca, Sanofi. A. Cortot: Financial Interests, Personal, Other, Consulting fees: Roche Novartis; Financial Interests, Personal, Other, Honoraria: Novartis Pfizer Takeda Roche; Financial Interests, Personal, Advisory Board: Roche Novartis Pfizer Takeda. All other authors have declared no conflicts of interest.