1304P - Investigator-initiated study of crizotinib in patients with MET activated advanced stage non-small cell lung cancer: A Canadian experience

Background

Currently in Canada, MET inhibitors are not funded for MET-driven lung cancer. We conducted a single-arm study of crizotinib, a Type1a oral tyrosine kinase inhibitor, to promote access and assess its efficacy as first line or subsequent therapy in patients with MET TKI naïve advanced NSCLC.

Methods

Eligible patients at the Princess Margaret Cancer Centre (Toronto, Canada) with advanced NSCLC harboring MET exon 14 skipping mutations or MET amplification (primary or acquired) received crizotinib 250 mg BID. The primary endpoint was response rate (ORR) by RECIST 1.1; other endpoints included progression-free survival (PFS), overall survival (OS), safety and plasma ctDNA correlates of response and resistance.

Results

Among 28 patients,19 had MET ^ex14 mutations, 9 had MET amplified lung cancer (7 EGFR mutant post TKI, 1 RET fusion post TKI). Median age was 68.5 (range 43-86), 68% were female, 48% Asian, 71% ECOG PS 1, and 46% received prior chemotherapy. The median treatment duration was 5.1 months (range 1-34). The ORR was 33% in the MET^amp and 53% in the MET ^ex14cohorts. Six patients had CNS-only progression. Grade ≥3 treatment-related adverse events were seen in 11 patients, most commonly anemia. At a median follow-up of 7.0 months (0.4-36.0), the median PFS was 6.2 months (95% CI 4.9-7.9), 1-yr PFS 23.3% (CI, 11.6-46.8%). The median OS was 8.7 months (95% CI 6.9-23.2) with 1-yr OS 42.9% (CI, 26.2-70.3%). Genomic correlates of response and resistance in plasma ctDNA will be presented.

Conclusions

Herein we provide real-world data that crizotinib yields clinically relevant ORR and PFS with acceptable toxicity in patients with advanced MET-driven NSCLC. MET targeted therapy is an important option for patients and should be accessible in the Canadian and other systems.

Clinical trial identification

NCT04084717.

Editorial acknowledgement

Legal entity responsible for the study

University Health Network

Funding

Princess Margaret Cancer Foundation.

Disclosure

G. Liu: Financial Interests, Personal, Advisory Board: Amgen, AnHeart, AstraZeneca, Bayer, EMD Serono, Jazz, Johnson and Johnson, Merck, Novartis, Pfizer, Roche, Sterimax, Takeda; Financial Interests, Personal, Coordinating PI: AstraZeneca, Takeda; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Pfizer, Takeda. N.B. Leighl: Other, Institutional, Other, Drugs/Research/Materials: Pfizer. All other authors have declared no conflicts of interest.