Tokyo’s Taiho and Cullinan Announce Positive Phase 3 Lung Cancer Results

Taiho Pharmaceutical Co., Ltd., its U.S. subsidiary Taiho Oncology, Inc., and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) said the Phase 3 REZILIENT3 trial met its primary endpoint of progression-free survival at a planned interim analysis. The global, multicenter, randomized, open-label study compares zipalertinib plus platinum-based chemotherapy with chemotherapy alone in adults with previously untreated, locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying EGFR exon 20 insertion mutations. The trial enrolled 285 patients.

The combination arm showed a statistically significant and clinically meaningful improvement in progression-free survival, with safety described as manageable. An Independent Data Monitoring Committee recommended unblinding the study based on the interim results, and the trial will continue to track efficacy and safety data going forward. The companies plan to submit full results for presentation at an upcoming international medical conference.

A Genetically Defined Subset With Few Options

Zipalertinib, also known by its development codes CLN-081 and TAS6417, is an orally available, irreversible small-molecule inhibitor engineered to target activating EGFR mutations, including variants carrying exon 20 insertions. Because platinum-based chemotherapy remains the standard frontline regimen for this population, an oral targeted option that improves on chemotherapy alone would fill a gap in first-line care.

EGFR exon 20 insertion mutations account for up to 4% of all NSCLC cases worldwide. In the United States, roughly 16% of NSCLC patients carry an EGFR mutation, and insertions at exon 20 make up as much as 12% of those mutations, according to genomic profiling data. Because the mutation defines a molecular subgroup rather than a single histology, diagnosis depends on routine genomic testing being available at the point of care, a step that still varies widely by health system.

Lung Cancer’s Global Burden Frames the Stakes

Lung cancer carries the heaviest burden of any tumor type worldwide. The World Health Organization’s Global Cancer Observatory recorded roughly 2.64 million new lung cancer cases in 2024, 12.8% of all cancer diagnoses globally, ranking it first by incidence. The disease also caused an estimated 1.86 million deaths that year, 19.1% of all cancer deaths, making it the leading cause of cancer mortality worldwide.

Non-small cell lung cancer accounts for the large majority of these cases, and molecular subtyping has increasingly separated the disease into biomarker-defined populations, each with its own treatment pathway and, in many cases, its own drug-development program. EGFR exon 20 insertion-positive disease sits within that broader shift: a comparatively small population in absolute terms, but one that trial sponsors can now target with purpose-built therapies rather than the broader chemotherapy and immunotherapy regimens used across unselected NSCLC.

Amivantamab Sets the Competitive Bar

Zipalertinib would enter a field already anchored by amivantamab, marketed as Rybrevant by Janssen, a Johnson & Johnson company. The FDA granted amivantamab accelerated approval in May 2021 for patients previously treated with platinum-based chemotherapy, then expanded the label in March 2024 to cover first-line use in combination with carboplatin and pemetrexed, based on the Phase 3 PAPILLON trial. In that trial, the amivantamab-chemotherapy combination extended median progression-free survival to 11.4 months, compared with 6.7 months for chemotherapy alone, a result published in the New England Journal of Medicine.

Currently, Rybrevant (amivantamab) can be delivered intravenously or via subcutaneous injection as a bispecific antibody targeting EGFR and MET, a mechanism and administration route distinct from zipalertinib’s oral, small-molecule design. If zipalertinib’s data hold up through full analysis and regulatory review, an oral option would give physicians and patients an alternative to infusion-based treatment in the first-line setting, though cross-trial comparisons of the two regimens are not yet available.

The Regulatory Path Ahead

Taiho Pharmaceutical, Taiho Oncology and Cullinan Therapeutics said they plan to pursue U.S. regulatory approval for the zipalertinib-chemotherapy combination in the first-line setting, pending discussions with the FDA. Zipalertinib has not been approved by any health authority, and the companies characterized the interim results as investigational pending full trial readout. Fabio Benedetti, global chief medical officer at Taiho Pharmaceutical, called the result an important milestone for a compound developed through the company’s own drug-discovery technology, while executives at Taiho Oncology and Cullinan Therapeutics pointed to the unmet need that persists in this mutation-defined patient population.

Otsuka’s Widening Oncology Footprint

Taiho Pharmaceutical operates as a subsidiary of Otsuka Holdings Co., Ltd., the Tokyo-based holding company that oversees Otsuka’s pharmaceutical, nutraceutical, consumer-product and other businesses. Otsuka Holdings reported consolidated revenue of ¥2,468.9 billion for fiscal 2025, with the pharmaceuticals segment contributing ¥1,744.2 billion of that total, according to the company’s investor relations disclosures. The group employed 37,758 people across 182 consolidated companies as of December 31, 2025, spanning 37 R&D sites and 111 manufacturing sites worldwide.

Within that structure, Taiho Pharmaceutical operates as an R&D-driven specialty pharma company focused on oncology and immune-related diseases, a position the REZILIENT3 result reinforces. Cullinan Therapeutics, a Nasdaq-listed biopharmaceutical company built around T cell engagers for autoimmune diseases and cancer, holds the U.S. collaboration rights to zipalertinib alongside Taiho, giving the smaller company a late-stage oncology asset inside a larger pipeline still centered on earlier-stage T cell engager programs.

Author

Bernice Lottering