FDA Approves Companion Diagnostic for Amivantamab in EGFR Exon 20–Positive NSCLC

Helmy Eltoukhy

The FDA has granted approval to the Guardant360 CDx liquid biopsy assay as the first companion diagnostic for amivantamab-vmjw (Rybrevant) to determine which patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations may derive benefit from the agent after progressing on, or after, platinum-based chemotherapy.¹

The regulatory agency gave the green light to amivantamab on May 21, 2021, for use in this patient population. The decision was based on data from the phase 1 CHRYSALIS trial (NCT02609776), in which amivantamab induced an overall response rate (ORR) of 40% (95% CI, 29%-51%), with a median duration of response (DOR) of 11.1 months (95% CI, 6.9–not reached [NR]) in pretreated patients with NSCLC harboring EGFR exon 20 insertion mutations.² Notably, 63% of the responders had their response persist for at least 6 months.

“Today’s FDA approval of Guardant360 CDx as a companion diagnostic for [amivantamab], the first targeted therapy to treat EGFR exon 20 mutations, is a key milestone for patients who, until now, have had limited treatment options,” Helmy Eltoukhy, chief executive officer of Guardant Health, stated in a press release. “We are proud to offer our Guardant360 CDx liquid biopsy blood test as a companion diagnostic so that patients may have access to comprehensive genomic profiling in order to see if they are eligible to receive this new treatment.”

The Guardant360 CDx uses a simple blood draw to provide comprehensive genomic results within 7 days; the test allows for the field to move beyond the limitations faced with tissue biopsies by making clinically relevant information rapidly available so that patients can be optimally matched with individualized treatment.

Notably, the test covers all genes that are recommended by the National Comprehensive Cancer Network, including those considered to be most relevant to care and treatment guidelines in this disease.

The CHRYSALIS trial was comprised of 2 phases: dose-escalation and -expansion. The recommended phase 2 dose (RP2D) was identified to be 1050 mg in patients who weighed less than 80 kg and 1400 kg in those who weighed 80 kg and above. Data presented during the 2020 World Conference on Lung Cancer Singapore included patients in the post-platinum setting who harbored exon 21 insertion mutations and were treated at the RP2D for the safety analysis (n = 114) and those with 3 or more disease assessments at the time of cutoff as part of the efficacy population (n = 81).³

The primary end point for the trial was ORR, while key secondary end points were clinical benefit rate (CBR), DOR, progression-free survival (PFS), and overall survival (OS).

Among those who responded to amivantamab, 3 achieved complete responses, 29 had partial responses, and 39 (48%) achieved disease stability. The CBR in this population was 74% (95% CI, 63%-83%). Ten percent of patients (n = 8) experienced disease progression.

Of the 63 patients with EGFR exon insertion mutations that were detectable in circulating tumor DNA, 25 distinct variants were observed in the helical (n = 1), near loop (n = 54), and far loop (n = 8) regions. However, these variations did not seem to impact response to treatment.

Additional data revealed that the median PFS achieved with amivantamab was 8.3 months (95% CI, 6.5-10.9), while the median OS was 22.8 months (95% CI, 14.6-NR).

Regarding safety, almost all participants experienced treatment-related adverse effects (TRAEs); 16% experienced TRAEs that were grade 3 or higher in severity. Nine percent of patients reported serious TRAEs and 4% had toxicities that resulted in discontinuation. Dose reductions that were considered to be associated with treatment were reported in 13% of patients, while treatment-related dose interruptions were experienced by 21% of patients.

The most frequent TRAEs reported with amivantamab included rash (86%), paronychia (42%), stomatitis (18%), and pruritis (17%); these were all related to EGFR inhibition. Effects associated with the MET pathway included hypoalbuminemia (15%) and peripheral edema (10%). Sixty-six percent of patients experienced infusion-related reactions and 12% were noted to have fatigue.

References

1. Guardant360 CDx receives FDA approval as companion diagnostic for Janssen’s RYBREVANT (amivantamab-vmjw) for use in patients with advanced non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. May 21, 2021. Accessed May 25, 2021. https://bit.ly/3vmj5Qw
2. FDA approves first targeted therapy for subset of non-small cell lung cancer. News release. FDA. May 21, 2021. Accessed May 25, 2021. https://prn.to/3hOrU1t
3. Sabari JK, Shu CA, Park K, et al. Amivantamab in post-platinum EGFR Exon 20 insertion mutant non–small cell lung cancer. J Thorac Oncol. 2021;16(3):S108-S109. doi:10.1016/10.1016/j.jtho.2021.01.284