Natasha B. Leighl, BSc, MMSc, MD, clinician investigator, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses efficacy findings with the EGFR/MET inhibitor amivantamab-vmjw (Rybrevant) in patients with advanced non–small cell lung cancer (NSCLC) harboring 

At the 2023 IASLC World Conference on Lung Cancer, Leighl presented updated findings from the ongoing phase 1 CHRYSALIS trial (NCT02609776) that investigated the efficacy of amivantamab monotherapy in patients with advanced NSCLC with 

 exon 14 skipping mutations whose disease had progressed on or who had declined the current regional standard-of-care therapy.

At a median follow-up of 10.0 months, 97 patients had received amivantamab in this trial. Of these patients, 16, 28, and 53 were treatment naïve, had prior treatment but no prior MET inhibitor, and a prior MET inhibitor, respectively. Common MET inhibitors used in prior lines of therapy included capmatinib (Tabrecta) and tepotinib (Tepmetko), Leighl says.

The overall response rate (ORR) in the entire population was 33%, with a median duration of response (DOR) of 11.2 months (95% CI, 5.3-19.0). Fifteenpatients had a DOR of at least 6 months, and 12 patients were still receiving the study treatment at the data cutoff date. Among the 49 patients who achieved stable disease, 48 experienced reductions in tumor size. In the cohorts of patients with treatment-naïve, no prior MET inhibition, and prior MET inhibition, the ORRs were 50%, 46%, and 21%, respectively. In addition, the clinical benefit rate (CBR) in the overall population was 70% (95% CI, 60%-79%), and the CBRs in the treatment naïve, no prior MET inhibition, and prior MET inhibition cohorts were 88% (95% CI, 62%-98%), 64% (95% CI, 44%-81%), and 68% (95% CI, 54%-80%), respectively. Median progression-free survival and overall survival were 5.4 months (95% CI, 4.3-7.0) and 15.8 months (95% CI, 13.1-21.8), respectively.

The most common treatment-emergent adverse effects (TEAEs) were rash, infusion-related reactions, and paronychia. Furthermore, 42% of patients experienced TEAEs of grade 3 or higher, and 20% of grade 3 or higher TEAEs were reported as treatment related.

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Natasha B. Leighl, BSc, MMSc, MD, discusses efficacy findings with the EGFR/MET inhibitor amivantamab in patients with advanced non–small cell lung cancer harboring MET exon 14 skipping mutations.
 

Dr Leighl on Amivantamab in Advanced NSCLC With MET Exon 14 Skipping Mutations

Natasha Leighl, MD, medical oncologist, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses binimetinib (Mektovi) in

-mutated non—small cell lung cancer (NSCLC).

The most common gene to be abnormal in NSCLC is RAS, Leighl says. Currently, there is no targeted therapy for this large population of patients, so they receive standard chemotherapy or immunotherapy.

-driven tumors rely on MEK to promote cancer survival, explains Leighl. Binimetinib is a potent oral inhibitor of MEK1 and MEK2, and it is a very well tolerated.

Binimetinib was approved by the FDA in June 2018 in combination with the BRAF inhibitor encorafenib (Braftovi) for the treatment of patients with 

mutant unresectable or metastatic melanoma, as detected by an FDA-approved test. Leighl says that based on this study in melanoma, investigators thought binimetinib might be a beneficial addition to frontline chemotherapy. At the 2018 International Lung Cancer Congress, Leighl presented data on the optimal dose of binimetinib with carboplatin and pemetrexed in patients with non-squamous NSCLC.

Natasha Leighl, MD, medical oncologist, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses binimetinib (Mektovi) in KRAS-mutated non–small cell lung cancer. 

Natasha Leighl, MD

Articles

Dr Leighl on Amivantamab in Advanced NSCLC With MET Exon 14 Skipping Mutations

Dr. Leighl Discusses Binimetinib in KRAS-Mutated NSCLC