Dr. Kelly on Overcoming Osimertinib Resistance in NSCLC With Bispecific Antibodies

Karen L. Kelly, MD, a professor, associate director for Clinical Research, and Jennifer Rene Harmon Tegley and Elizabeth Erica Harmon Endowed Chair in Cancer Clinical Research at the University of California Davis, discusses overcoming osimertinib (Tagrisso) resistance in patients with non–small cell lung cancer through the use of bispecific antibodies.

Amivantamab-vmjw (Rybrevant) is a bispecific to EGFR and MET that has demonstrated activity in patients who have developed osimertinib resistance, yielding a promising objective response rate as a monotherapy, according to Kelly. However, the concern with utilizing a monoclonal antibody in this setting is that it will not cross the blood brain barrier, she says. As such lazertinib (YH25448), a third generation TKI that is fairly similar to osimertinib, is a highly efficacious option that is capable of crossing the blood brain barrier with a low toxicity profile.

The theory is that by combining the 2 agents, further activity may be achieved, Kelly says. This formed the rationale for the phase 1 CHRYSALIS study (NCT02609776), which examined the combination in patients who had progressed on osimertinib but had not received standard of care chemotherapy. Findings from the study indicated that patients achieved a response rate of approximately 36% and a median progression-free survival of 4.9 months. When patients were stratified based on EGFR/MET dependence, the response rate increased to 47%, Kelly concludes.