Dr Lisberg on Emerging Post-Osimertinib Treatment Options in EGFR-mutant NSCLC

Aaron Lisberg, MD, assistant professor of medicine, hematologist, thoracic medical oncologist, University of California, Los Angeles (UCLA) Health, discusses ongoing and future efforts to expand effective treatment options for patients with osimertinib (Tagrisso)-resistant, EGFR-mutant non–small cell lung cancer (NSCLC).

The phase 1 Chrysalis-2 trial (NCT04077463) is evaluating the use of the EGFR TKI lazertinib (Laclaza) alone and in combination with the bispecific antibody amivantamab-vmjw (Rybrevant) for patients with EGFR-mutant NSCLC. Those patients who progressed on prior treatment with osimertinib and platinum-based chemotherapy were enrolled to cohort A of the dose-expansion portion of the study.

Updated results from cohort A were previously presented at the 2022 ASCO Annual Meeting, and they showed that the combination of lazertinib plus amivantamab produced an overall response rate of 33% (95% CI, 26%-41%) and a median duration of response of 9.6 months (95% CI, 7.0–not evaluable) in these patients, who harbored EGFR exon 19 deletions or L858R mutations. The safety profile of this regimen was also consistent with prior reports, and these data support the continued exploration of the combination in a larger patient population, Lisberg says.

Other emerging agents in the post-osimertinib space include the antibody-drug conjugates patritumab deruxtecan (HER3-DXd) and datopotamab deruxtecan (Dato-DXd; DS-1062a), Lisberg continues.

HER3 is particularly overexpressed in EGFR-mutant NSCLC after osimertinib progression, making this target a viable candidate for exploration, Lisberg states. In a phase 1 trial (NCT03260491) of previously treated patients with EGFR-mutated metastatic or unresectable NSCLC, HER3-DXd was shown to generate responses and be well-tolerated.

Meanwhile, the TROP-2 targeted agent Dato-DXd is currently being explored in patients who have NSCLC with or without actionable genomic alterations, Lisberg continues. Current data indicate that the agent has shown efficacy in both populations, he adds. Findings previously presented at the 2021 ESMO Congress from the phase 1 TROPION-PanTumor01 trial (NCT03401385) highlighted the agent's promising response rate and safety in patients with NSCLC harboring genetic alterations, including EGFR mutations, Lisberg notes.

Future data will hopefully continue to support the viability of these novel strategies for patients with NSCLC and acquired osimertinib resistance, Lisberg concludes.

Disclosures: Dr Lisberg reported receiving consultant/advisory board fees from AstraZeneca, Bristol Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys, Eli-Lilly, Oncocyte, Novartis, Regeneron, Janssen Incology, and Sanofi; commercial research grants from Daiichi Sankyo, Calithera Biosciences, AstraZeneca, Dracen Pharmaceuticals, WindMIL, and eFFECTOR Therapeutics; and employment and equity interest from Boston Scientific.