A phase 2 signal-finding basket trial investigating oral ponatinib in solid tumors harboring specific gain-of-function genomic alterations did not meet its primary endpoint in patients with FGFR alterations. Although the multi-target tyrosine kinase inhibitor did not achieve the prespecified response threshold in this group, researchers reported that the regimen yielded prolonged disease control in several patients alongside manageable toxicity.
Genomic alterations across tyrosine kinase receptors, including FGFR, KIT, RET, VEGFR, and PDGFRα, function as driver mutations in many solid tumors, presenting an unmet need particularly for inhibitors of FGFR1.
Designed to assess the efficacy and safety of oral ponatinib in solid tumors with select gain-of-function alterations, the basket trial set overall response rate as the primary endpoint. Key secondary endpoints included progression-free survival, overall survival, and safety. A total of 22 enrolled patients took part in the study, and all 22 were included in the prespecified primary efficacy analysis.
In the primary cohort, designated as cohort A for patients with FGFR alterations, the overall response rate was 5.9% (1 of 17 patients). The median progression-free survival in cohort A was 1.9 months with a 95% confidence interval of 0.5 to 3.9 months, and the median overall survival was 5.3 months with a 95% confidence interval of 3.4 to 25.0 months. In the secondary cohort, designated as cohort B for patients with RET, KIT, VEGFR, or PDGFRα alterations, the overall response rate was 0% (0 of 5 patients), with a median progression-free survival of 9.5 months and a median overall survival of 11.8 months.
The study authors concluded that ponatinib is not a therapy of choice for patients with FGFR alterations. However, because ponatinib is a potent inhibitor of FGFR family members—particularly FGFR1—as well as KIT, RET, VEGFR, PDGFRα, and other tyrosine kinase proteins, the authors noted that it could be considered for patients who are intolerant of FGFR-selective inhibitors.
Subject of Research: Phase 2 basket trial evaluating oral ponatinib in solid tumors with FGFR and other tyrosine kinase alterations
Article Title: Phase 2 basket trial of ponatinib in tumors with FGFR alterations and other genomic targets
Article References: Risch, Z., Reeser, J., Wing, M., Hays, J., Noonan, A., Damodaran, S., Smith, A., Dao, T., Samorodnitsky, E., Pan, X., & Roychowdhury, S. (2026). Phase 2 basket trial of ponatinib in tumors with FGFR alterations and other genomic targets. BMC Cancer. https://doi.org/10.1186/s12885-026-17235-0
Image Credits: AI Generated
DOI: 10.1186/s12885-026-17235-0
Keywords: ponatinib, FGFR alterations, solid tumors, basket trial, phase 2 clinical trial, tyrosine kinase inhibitors, oncology, cancer research, Phase, basket, trial, tumors
