NEW YORK – Taiho Pharmaceutical and Cullinan Oncology on Friday said they launched a Phase III trial of the EGFR inhibitor zipalertinib as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer harboring the EGFR exon 20 insertion mutation.
In the REZILIENT3 trial, researchers from Taiho Oncology, a subsidiary of Princeton, New Jersey-based Taiho Pharmaceutical, and Cullinan, which is headquartered in Cambridge, Massachusetts, are evaluating the efficacy and safety of zipalertinib with standard chemotherapy in this patient group in two parts. Part A of the trial is a safety lead-in study to determine a recommended dose, and Part B is a randomized, controlled, open-label Phase III trial to assess efficacy and safety of the drug at that recommended dose, compared to chemotherapy alone. About six to 12 patients will be enrolled in Part A and 300 patients in Part B.
In a previous Phase I/IIa trial, patients with NSCLC harboring EGFR exon 20 insertion mutations had a partial response rate of 38.4 percent, or 28 out of 73 participants, demonstrating preliminary antitumor activity.
Up to 4 percent of patients with NSCLC have EGFR exon 20 insertions, which account for up to 12 percent of all EGFR mutations.
"Patients with NSCLC who have EGFR exon 20 insertion mutations are known to have poorer outcomes than those with more common EGFR mutations," Taiho Oncology Senior VP Volker Wacheck said in a statement. "Advancing care for this subset of patients with NSCLC is essential to advancing care in NSCLC overall."
In addition to zipalertinib, Taiho is also advancing its FGFR 1-4 inhibitor futibatinib in two Phase II trials in urothelial cancer in combination with Merck's Keytruda (pembrolizumab), and in non-small cell lung cancer with KRAS mutations in combination with Pfizer's Mektovi (binimetinib).