As reported in the Journal of Clinical Oncology by Keunchil Park, MD, PhD, and colleagues, amivantamab-vmjw given at the selected phase II dose in a phase I trial (CHRYSALIS) produced durable responses in patients with EGFR exon 20 insertion–mutated non–small cell lung cancer (NSCLC) whose disease progressed on platinum-based chemotherapy. The findings supported the May 2021 accelerated approval of amivantamab in this setting.

Keunchil Park, MD, PhD

As stated by the investigators, “Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor’s extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site.”

Study Details

The study enrolled patients between May 2016 and June 2020 from sites in Korea, the United States, and Japan. The current report presents findings in 81 patients in the pivotal efficacy population, consisting of the first 81 patients enrolled who received the recommended phase II dose of 1,050 mg (1,400 mg in patients > 80 kg) given via intravenous infusion once weekly for the first 4 weeks and then once every 2 weeks starting at week 5. The safety population included 114 patients receiving the phase II dose by June 2020. In the efficacy population, the median age was 62 years, 49% of patients were Asian, and the median number of previous lines of therapy was two (range = 1–7).

Responses

At the efficacy data cutoff (October 2020), median follow-up was 9.7 months (range = 1.1­–29.3 months).

Objective response on blinded independent central review was observed in 32 patients (40%, 95% confidence interval [CI] = 29%–51%), including complete response in 3 (4%). An additional 34 patients had stable disease for ≥ 11 weeks, yielding a clinical benefit rate of 74% (95% CI = 63%–83%). Median duration of response was 11.1 months (95% CI = 6.9 months–not reached).

Median progression-free survival was 8.3 months (95% CI = 6.5–10.9 months). Overall survival data were not mature, with death occurring in 23 patients at time of analysis. Median overall survival at the time of analysis was 22.8 months (95% CI = 14.6 months–not reached).  

Adverse Events

In the safety population, the most common adverse events of any grade were rash (86%), infusion-related reactions (66%), and paronychia in (45%). Grade 3 or 4 adverse events were observed in 35% of patients, with the most common being hypokalemia (5%) and rash, pulmonary embolism, diarrhea, and neutropenia (4% each). Serious adverse events occurred in 30% of patients, the most common being pulmonary embolism and back pain (3% each). Treatment was discontinued due to treatment-related adverse events in 4%, with causes consisting of rash and infusion-related reaction in two patients each and paronychia in one. No treatment-related deaths were reported.

The investigators concluded, “Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with EGFR exon 20 insertion–mutated [NSCLC] after progression on platinum-based chemotherapy.”

Byoung Chul Cho, MD, PhD, of the Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Janssen R&D LLC. For full disclosures of the study authors, visit ascopubs.org.