Therapy With Bispecific Antibody for EGFR Exon 20 Insertion–Mutated NSCLC

Amivantamab Shows Strong Efficacy in NSCLC With EGFR Exon 20 Insertion

Erminia Massarelli, MD, PhD, MS, discusses the efficacy outcomes of the CHRYSALIS trial of amivantamab in patients with non–small cell lung cancer and an EGFR exon 20 insertion.

Erminia Massarelli, MD, PhD, MS, codirector of the lung cancer and thoracic oncology program, section chief of thoracic oncology, and associate professor in the department of medical oncology and therapeutics research at City of Hope, discusses the efficacy outcomes of the CHRYSALIS trial (NCT02609776) of amivantamab (Rybrevant) in patients with non–small cell lung cancer (NSCLC) and an EGFR exon 20 insertion.

Eighty-one patients from cohorts A and D of the phase 1 study were assessed after receiving amivantamab following progression on platinum-based chemotherapy. The overall response rate (ORR) was 40% (95% CI, 29%-51%) including 3 complete responses (CRs). The median duration of response (DOR) was 11.1 months (95% CI, 6.9–not reached) and the median progression-free survival (PFS) was 8.3 months (95% CI, 6.5-10.9).

A subset analysis of the EGFR exon 20 insertions in these patients with NSCLC analyzed the location of the insertion based on circulating tumor DNA (ctDNA) or tumor samples. The only patient with a mutation in the helical region had a confirmed response to amivantamab. Out of 54 patients with the insertion in the near-loop region, 41% had responses. Out of 8 patients with an insertion in the far-loop region, 25% had responses. Investigators were not able to identify the site of the mutation by ctDNA in 18 patients. Massarelli says this could potentially identify the likelihood of responding and the depth of response to amivantamab.

TRANSCRIPTION:

0:08 | The ORR was 40% and included 3 CRs with a median DOR of 11.1 months. The median PFS was 8.3 months, and the tumor reduction was significant. There were several CRs, as we said 3. But there was also a subset analysis about the exon 20 insertion locations. What they found was that—they were divided in a helical region, near loop, far loop, and not detected. The ones that did the best, apparently, were the helical region insertion that had a response rate of 100%. The second best were the near loop, which had 41%. And then the far loop actually had 25%. I think also knowing the location of this insertion might actually predict the response, even if we need more information with a larger cohort of patients.