Dr. Paik on Tepotinib in METex14-Mutated NSCLC

Paul K. Paik, MD, associate attending physician, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, discussed using tepotinib — a highly selective, ATP-competitive, reversible, potent MET TKI – to treat patients with non–small cell lung cancer (NSCLC) with MET exon 14 skipping (METex14) mutations.

METex14 mutations are reported in approximately 3% to 4% of patients with NSCLC. In the phase II VISION study, 85 patients were enrolled and had detected METex14 mutations, 55 were detected using liquid biopsies, and 52 were detected using tumor biopsies. Patients received 500 mg of tepotinib daily until progression, intolerable toxicity, or withdrawal. In evaluable liquid biopsy patients, the objective response rate (ORR) was 50% by independent central review (IRC) and 55.3% by investigator assessment. In 51 evaluable tumor biopsy patients, ORR was 45.1% by IRC and 54.9% by investigator assessment.

Any grade treatment-related adverse events (TRAEs), reported by ≥10% of 69 patients evaluable for safety, included peripheral edema (48.3%), nausea (23.0%), diarrhea (20.7%), blood creatinine increased (12.6%), and asthenia (9.2%). No TRAEs were grade 4 or 5. No TRAEs led to death but led to permanent discontinuation in 4 patients.

Tepotinib showed durable clinical activity in patients with NSCLC and METex14 mutations and had a favorable safety profile. Recruitment for this trial is ongoing.