KEY TAKEAWAYS
- The FIGHT-101 study (NCT02393248) looked at advanced refractory cancers with and without fibroblast growth factor (FGF) and receptor (FGFR) gene changes.
- The study aimed to assess the safety, pharmacokinetics, pharmacodynamics, and early efficacy of pemigatinib as monotherapy or in combination therapy
- Part 1 (dose escalation; 3 + 3 design) aimed to find the maximum tolerable dose in molecularly unselected patients with advanced malignancies.
- The suggested phase II dose was analyzed for tumors with or without FGF/FGFR activity in Part 2 (dose expansion).
Pemigtinib 1-20 mg once daily was administered to patients (N = 128) either sporadically (2 weeks on/1 week off; n = 70) or continuously (n = 58). There were no reports of fatalities caused by the dose. The pharmacological activity was observed at doses 4 mg (maximum tolerated dose not reached; recommended phase II dose 13.5 mg once daily). Hyperphosphatemia (75.0%; grade 3, 2.3%) and fatigue (10.2%) were the most common treatment-emergent adverse events (TEAEs). Sixty-six (51.6%) patients experienced dosage interruption, 14 (10.9%) experienced dose decrease, and 13 (10.2%) discontinued treatment altogether because of TEAE. Altogether, 12 partial responses were seen across a wide range of tumor types, including cholangiocarcinoma (n = 5), head and neck cancer, pancreatic cancer, gallbladder cancer, uterine cancer, urothelial cancer, recurrent pilocytic astrocytoma, and non-small-cell lung cancer (each n = 1). The median duration of response was 7.3 months [95% CI, 3.3-14.5 months]. Patients with FGFR fusions/rearrangements (n = 5; 25.0% (95% CI 8.7% to 49.1%)) had the greatest overall response rate, followed by patients with FGFR mutations (n = 3; 23.1% (95% CI 5.0% to 53.8%).
Responses were reported across tumor types and were fueled by FGFR fusions/rearrangements and mutations, although the drug’s safety profile was acceptable. Because of these findings, researchers decided to do a registrational study on cholangiocarcinoma and conduct phase II/III studies on multiple tumor types to further prove the efficacy of precision medicine at such an early stage.
Source: https://pubmed.ncbi.nlm.nih.gov/35176457/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02393248
Subbiah, V., Iannotti, N. O., Gutierrez, M., Smith, D. C., Féliz, L., Lihou, C. F., Tian, C., Silverman, I. M., Ji, T., & Saleh, M. (2022). FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies. Annals of oncology : official journal of the European Society for Medical Oncology, 33(5), 522–533. https://doi.org/10.1016/j.annonc.2022.02.001
