Evolving NSCLC Treatment Paradigm

Updated phase 2 data showed a 60% ORR and 86% CNS ORR with frontline silevertinib in non-classical EGFR-mutant NSCLC; FDA discussion supported a phase 3 trial in 2027.

The NDA was completed for first-line zipalertinib plus platinum chemotherapy in EGFR exon 20 insertion NSCLC, based on phase 3 REZILIENT3 data showing improved PFS.

Telisotuzumab adizutecan showed promising survival in pretreated nonsquamous NSCLC, with the most benefit in EGFR wild-type tumors with high c-Met levels.

FDA issues a not approvable letter for Novocure’s Optune Mya in NSCLC brain metastases, citing uncertain clinical benefit. No safety concerns were raised.

Imneskibart showed promising outcomes and tolerability in patients who had previously received immune checkpoint inhibition for either melanoma or lung adenocarcinoma.

In KEYNOTE-867, adding pembrolizumab to radiotherapy did not extend event-free survival in inoperable early-stage NSCLC and raised toxicity; the phase 3 trial was stopped for futility in 2024.