Zipalertinib Plus Chemotherapy Moves to Phase 3 Study in EGFR Exon 20 Insertion+ NSCLC

The safety and efficacy of zipalertinib (CLN-081, TAS6417) plus platinum-based chemotherapy will be compared with platinum-based chemotherapy alone in patients with treatment-naïve, locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations in the phase 3 REZILIENT3 trial (NCT05973773).¹

Previously, results from a phase 1/2a trial (NCT04036682) that were presented at the 2022 ASCO Annual Meeting and subsequently published in the Journal of Clinical Oncology showed a 38.4% partial response rate in 73 evaluable patients with recurrent or metastatic EGFR exon 20 insertion–mutant NSCLC following prior platinum-based chemotherapy.^2,3

“Patients with NSCLC who have EGFR exon 20 insertion mutations are known to have poorer outcomes than those with more common EGFR mutations,” Volker Wacheck, MD, PhD, senior vice president, Clinical Development, Taiho Oncology, Inc, stated in a press release. “Advancing care for this subset of patients with NSCLC is essential to advancing care in NSCLC overall.”

Zipalertinib is a next-generation oral, irreversible, small molecule designed to target EGFR activating mutations, including EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. In January 2022, the FDA granted breakthrough therapy designation to zipalertinib for the treatment of patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations and who have received prior platinum-based chemotherapy.⁴

REZILIENT3 is a global, multicenter, open-label, randomized controlled trial seeking to enroll approximately 312 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC with EGFR exon 20 insertion mutations.¹

Progression-free survival will serve as the primary end point of the trial.

“The initiation of the phase 3 trial for zipalertinib in the first-line setting is an important step forward for this clinical research program, as it represents an opportunity for zipalertinib to help more patients with EGFR exon 20 insertion mutation NSCLC,” Jeffrey Jones, MD, MPH, MBA, chief medical officer, Cullinan Oncology, Inc., stated in a press release. “We look forward to working with our partners at Taiho to rapidly assess zipalertinib in the front line, while in parallel continuing to advance our pivotal phase 2b trial in patients who have received prior systemic treatment for locally advanced or metastatic disease.”

References

1. Rezilient3 global first-line trial of zipalertinib launched in patients with non-small cell lung cancer harboring EGFR exon 20 insertion mutations. News release. Taiho Oncology. August 3, 2023. Accessed August 4, 2023. https://www.taihooncology.com/us/news/2023-08-03_zipalertnib_phase3/
2. Yu HA, Tan DSW, Smit EF, et al. Phase (Ph) 1/2a study of CLN-081 in patients (pts) with NSCLC with EGFR exon 20 insertion mutations (Ins20). J Clin Oncol. 2022;40(suppl 16):9007. doi:10.1200/JCO.2022.40.16_suppl.9007
3. Piotrowska Z, Tan DSW, Smit EF, et al. Safety, tolerability, and antitumor activity of zipalertinib among patients with non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions. J Clin Oncol. Published online June 29, 2023. doi:10.1200/JCO.23.00152
4. FDA grants breakthrough therapy designation for Cullinan Oncology’s CLN-081 in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer. News release. Cullinan Oncology, Inc.; January 4, 2022. Accessed August 4, 2023. https://investors.cullinanoncology.com/news-releases/news-release-details/fda-grants-breakthrough-therapy-designation-cullinan-oncologys