Amivantamab Induces Responses in Patients With METex14-Positive NSCLC

Alexander Spira, MD, PhD, FACP

Treatment with amivantamab-vmjw (Rybrevant) in the phase 1 CHRYSALIS study has released anti-tumor activity in patients with non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping (METex14) mutations treated with the agent, according to a press release by the Janssen Pharmaceutical Companies of Johnson & Johnson.¹

"Newer treatment advances for non-small cell lung cancer provide benefit to patients with MET exon 14 skipping mutations, but because they are effective for only a finite period of time, patients ultimately find themselves in need of new therapies," said Alexander Spira, MD, PhD, FACP, director of the Virginia Cancer Specialists Research Institute, co-chair US Oncology Thoracic Program and presenting study investigator.

The phase 1 first-in-human, open-label, dose-escalation CHRYSALIS study (NCT02609776) is evaluating the efficacy and safety of amivantamab in patients with METex14-positive NSCLC. The primary end points include the number of adverse events (AEs) and serious AEs, objective response rate (ORR), duration of response (DOR), and clinical benefit rate (CBR).² The key secondary end points of the study include progression-free survival (PFS), overall survival (OS), and time to treatment failure.

Nineteen patients in the CHRYSALIS study were treated with amivantamab 1050 mg for patients <80 kg or1400 mg for patients who weigh ≥80 kg. Fourteen patients were evaluable for response, and of those patients, 64% had a partial response to therapy, regardless of prior lines of therapy. Notably, 4 of the 7 responders were previously treated with a MET tyrosine kinase inhibitor.¹

The median time to first response observed was 4.1 months (range, 1-9.9).

In terms of safety, most treatment-related AEs (TRAEs) were grades 1 and 2, and 16% of patients experienced grade 3 or higher AEs. The grade 3 AEs observed in the study subjects were dyspnea, hypoalbuminemia, and rash, which occurred in 1 patient each. TRAEs led to dose reduction in 11% of patients and discontinuation of treatment in 5%. Further, 32% of patients had dose interruption due to TRAEs.

Positive results from the CHRYSALIS study comes on the heels of an accelerated FDA approval granted to amivantamab for the frontline treatment of adult patients with NSCLC whose tumors have EGFR exon 20 insertion mutations. Approval was granted based on earlier results from the CHRYSALIS.³

In 63 patients with EGFR exon 20-positive NSCLC who were followed for a median of 9.7 months (range, 1.1-29.3), the ORR was 40% (95% CI, 29%-51%), which included 3 complete responses and 29 partial responses. Stable disease was noted in 39 patients (48%), and 8 (10%) had progressive disease for a clinical benefit rate of 74% (95% CI, 63%-83%). The median duration of response was 11.1 months (95% CI, 6.9-not reached [NR]).⁴

In terms of survival, the median PFS was 8.3 months (95% CI, 6.5-10.9) and the median OS was 22.8 months (95% CI, 14.6%-NR).

TRAEs occurred in almost all patients, with 16% of patients experienced grade 3 or higher TRAEs. Serious TRAEs were observed in 9%, and 4% had treatment-related events that led to discontinuation. Dose reductions and interruptions deemed to be related to therapy were seen in 13% and 21%, respectively.

Regarding Amivantamab for the treatment of METex14-positive NSCLC, Kiran Patel, MD, vice president, clinical development, solid tumors, Janssen Research & Development, LLC said, in a press release:¹ "While the recent FDA approval of Rybrevant was an important milestone for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations, there continues to be a lack of long-term treatment options for patients with other mutations, including MET exon 14 skipping mutations. "We are encouraged by these data showing evidence that Rybrevant can lead to broad activity against both EGFR and MET-driven tumors."

"We look forward to sharing these latest results for amivantamab that suggest its novel mechanism of action may be of benefit to people living with this type of lung cancer, said Spira, in a statement to the press.

_Reference:

_{1. Janssen Presents phase 1 results for RYBREVANT™ (amivantamab-vmjw) in the treatment of patients with advanced non-small cell lung cancer with MET exon 14 skipping mutations. News release. August 19, 2021. Accessed August 19, 2021. https://bit.ly/37ZHOjo}

_{2. Study of amivantamab, a human bispecific EGFR and cMet antibody, in participants with advanced non-small cell lung cancer (CHRYSALIS). Clinicaltrials.gov. Accessed August 19, 2021.}

_{3. FDA approves first targeted therapy for subset of non-small cell lung cancer. News release. FDA. May 21, 2021. Accessed August 19, 2021. https://bit.ly/3fCjEyT}

_{4. Sabari JK, Shu CA, Park K, et al. Amivantamab in post-platinum EGFR Exon 20 insertion mutant non–small cell lung cancer. Presented at: IASLC 2020 World Conference on Lung Cancer Singapore. January 28-31, 2021. Abstract OA04.04}