Dr Goldberg on Investigational Agents in EGFR-mutant NSCLC

Sarah Goldberg, MD, MPH, associate professor, internal medicine (medical oncology), associate director, Medical Oncology-Hematology Program, research director, Center for Thoracic Cancers, chief, Thoracic Oncology, Yale School of Medicine, discusses ongoing investigations with antibody-drug conjugates (ADCs) and bispecific antibodies in patients with non–small cell lung cancer (NSCLC) harboring EGFR mutations.

As ADCs continue to broaden the NSCLC treatment paradigm across disease subtypes, the HER3-directed ADC patritumab deruxtecan (HER3-DXd) is a notable investigational agent in patients with EGFR-mutant disease, Goldberg says. In the phase 1 U31402-A-U102 trial (NCT03260491), at a median follow-up of 23 months, patritumab deruxtecan generated an overall response rate (ORR) of 40.2% in the cohort of patients with EGFR-mutated NSCLC, including 1 complete response (CR) and 40 partial responses (PRs). Based on the findings from that trial, in 2021, the FDA granted a breakthrough therapy designation to patritumab deruxtecan for patients with metastatic or locally advanced EGFR-mutated NSCLC who have progressed on or after a third-generation TKI and platinum-based therapy.

In addition, the bispecific antibody amivantamab-vmjw (Rybrevant) was approved by the FDA in 2021 for patients with NSCLC harboring EGFR exon 20 insertion mutations. In the pivotal trial, amivantamab elicited an ORR of 40% along with a median duration of response of 11.1 months.

Amivantamab may also be effective in patients with EGFR-mutant disease after progression on an EGFR inhibitor, Goldberg explains. Findings from the phase 1 CHRYSALIS-2 trial (NCT04077463), which evaluated the agent in combination with the EGFR TKI lazertinib, showed that treatment with the combination led to a 36% ORR, including 1 CR and 17 PRs in patients who had progressed on osimertinib and platinum-based chemotherapy.

As these agents and others emerge in the EGFR-mutated NSCLC treatment landscape, the next steps will include determining effective predictive biomarkers, Goldberg notes. As patients with NSCLC have achieved positive outcomes with patritumab deruxtecan, amivantamab, and other drugs and drug combinations, additional data may further support their use in the EGFR-mutated population, Goldberg concludes.