Pemigatinib Demonstrates Activity in Previously Treated Solid Tumors Harboring Activating FGFR Alterations


Pemigatinib generated efficacy and tolerability in previously treated patients with advanced/metastatic or unresectable solid tumors harboring activating FGFR mutations or fusions/rearrangements, including cholangiocarcinoma, central nervous system tumors, gynecologic tumors, and pancreatic cancer.

Jordi Rodón, MD, PhD

Jordi Rodón, MD, PhD

Pemigatinib (Pemazyre) generated efficacy and tolerability in previously treated patients with advanced/metastatic or unresectable solid tumors harboring activating FGFR mutations or fusions/rearrangements, including cholangiocarcinoma, central nervous system (CNS) tumors, gynecologic tumors, and pancreatic cancer, according to data from the phase 2 FIGHT-207 trial (NCT03822117; EudraCT 2018-004768-69).1

Findings presented at the 2023 AACR Annual Meeting showed that patients with FGFR fusions or rearrangements (n = 49; cohort A) experienced an objective response rate (ORR) of 26.5% (95% CI, 15.0%-41.1%) and a disease control rate (DCR) of 65.3% (95% CI, 50.4%-78.3%). Those harboring FGFR actionable single nucleotide variants (n = 32; cohort B) had an ORR of 9.4% (95% CI, 2.0%-25.0%) and a DCR of 56.3% (95% CI, 37.7%-73.6%). Patients with FGFR kinase domain mutations or a variant of unknown significance (n = 26; cohort C) had an ORR of 3.8% (95% CI, 0.1%-19.6%) and a DCR of 34.6% (95% CI, 17.2%-55.7%).

“We saw significant activity in cholangiocarcinoma with FGFR fusions...We [also] saw significant activity in mutations both in the extracellular domain ligand binding and the transmembrane domain,” lead study author Jordi Rodón, MD, PhD, said in a presentation of the data. Rodón is an associate professor in the Department of Investigational Cancer Therapeutics in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

Pemigatinib is a selective, potent, oral FGFR1-3 inhibitor that previously produced a manageable safety profile, plus pharmacodynamic and clinical activity, in pretreated patients with FGF/FGFR-altered solid tumors in the phase 1/2 FIGHT-101 trial (NCT02393248).2

In August 2022, the FDA approved pemigatinib for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms and FGFR1 rearrangement.3

The open-label, single-arm FIGHT-207 basket trial further evaluated pemigatinib in patients with unresectable or advanced/metastatic solid tumors who had a confirmed activating FGFR mutation or fusion/rearrangement.

All patients in cohorts A, B, and C received continuous pemigatinib at 13.5 mg per day for 21-day cycles until they experienced disease progression or unacceptable toxicity.

Independent central review–confirmed ORR per RECIST v1.1 or Response Assessment in Neuro-Oncology criteria in cohorts A and B served as the trial’s primary end point. Secondary end points consisted of progression-free survival (PFS), duration of response (DOR), and overall survival (OS) in cohorts A and B, as well as safety in all cohorts.

“Cohort C [was] a more exploratory [group] where we included patients with mutations in the kinase domain, as well as other [FGFR] variants of unknown significance that we thought could be actionable, but were not well identified clinically,” Rodón said.

A translational analysis also featured a Foundation Medicine, Inc. co-alteration analysis, as well as circulating tumor DNA (ctDNA) at baseline and at progression using the 152-gene PredicineCare Assay.

At data cutoff, all patients in all 3 cohorts had discontinued treatment. In cohort A, reasons for discontinuation included progressive disease (67.3%), physician decision (4.1%), adverse effects (AEs; 6.1%), patient withdrawal (6.1%), study terminated by sponsor (8.2%), and other (8.2%). In cohort B, reasons for discontinuation were progressive disease (96.9%) and death (3.1%). Patients in cohort C discontinued treatment due to progressive disease (65.4%), AEs (11.5%), patient withdrawal (7.7%), study terminated by sponsor (3.8%), death (7.7%), or other (3.8%).

Across all patients (n = 111), the median age was 62.0 years (range, 25-84), and 55.9% of patients were female. Most patients (95.5%) had an ECOG performance status of 0 or 1. Additionally, 55.9% of patients received 2 or more prior lines of systemic therapy, and 44.1% of patients had 0 or 1 prior lines of systemic therapy.

The most common tumor types in the overall population included cholangiocarcinoma (16.2%), gynecologic (12.6%), CNS (11.7%), urothelial/bladder cancer (10.8%), pancreatic cancer (7.2%), non–small cell lung cancer (NSCLC; 6.3%), and breast cancer (5.4%). (Table)

Additional data from cohort A showed the median DOR was 7.8 months (95% CI, 4.2-not estimable [NE]). These patients achieved a median PFS of 4.5 months (95% CI, 3.6-6.3) and a median OS of 17.5 months (95% CI, 7.8-NE).

In cohort B, patients experienced a median DOR of 6.9 months (95% CI, 4.0-NE), a median PFS of 3.7 months (95% CI, 2.1-4.5), and a median OS of 11.4 months (95% CI, 16.6-NE).

The median PFS and median OS for patients in cohort C was 2.0 months (95% CI, 1.8-3.7) and 11.0 months (95% CI, 3.9-NE), respectively. Median DOR data were not available.

Regarding safety, the toxicity profile for pemigatinib was generally consistent with prior findings. The most common treatment-emergent AEs included hyperphosphatemia (any grade, 83.8%; grade ≥3, 0.9%), stomatitis (53.2%; 9.0%), alopecia (40.5%; 0.9%), diarrhea (38.7%; 0.9%), and constipation (33.3%; 0.9%).

Findings from the translational analysis showed that responses were observed across all cohorts, including in patients who harbored FGFR alterations that were not previously considered actionable or previously uncharacterized FGFR alterations. Most responses were reported in patients with cholangiocarcinoma, CNS tumors, gynecologic tumors, and pancreatic tumors with actionable FGFR alterations.

Furthermore, tissue analysis showed that co-alterations in BAP1 and TP53 were mutually exclusive in baseline archival tumor samples. BAP1 co-alterations were significantly associated with response, and TP53 co-alterations were generally associated with poor response. Among tissue-evaluable patients in the overall population who achieved a response (n = 15), 46.7% had a BAP1 co-alteration, and none had a TP53 co-alteration. Among those who had stable disease or progressive disease (n = 57), 3.5% had a BAP1 co-alteration, and 40.4% harbored a TP53 co-alteration.

A pathway analysis using tissue and ctDNA showed that co-alterations in the MAPK and PI3K pathway genes were generally associated with a lack of response.

An analysis of FGFR resistance mutations in ctDNA at baseline and disease progression showed that FGFR baseline mutations in “molecular brake” residues were generally associated with progressive disease. Moreover, FGFR gatekeeper and molecular brake mutations were detected at disease progression.

At disease progression, the most frequent emergent pathogenic variants by ctDNA included FGFR2, TP53, PIK3CA, KRAS, NRAS, FGFR3, FGFR1, ARID1A, KIT, ATM, BRCA2, and HRAS.

Disclosures: Dr Rodón reported serving as a consultant for AADi, Cullgen, Debiopharm Group, Ellipses Pharma, iOnctura, Macrogenics, Merus, Monte Rosa Therapeutics, Oncology One, Pfizer, Sardona Therapeutics, Vall d’Hebron Institute of Oncology, Avoro Capital Advisors, Boxer Capital, Chinese University of Hong Kong, Clarion Healthcare, Columbus Venture Partners, Envision Pharma Group, and Tang Advisors; and receiving personal grant/research support from Black Diamond Therapeutics, Blueprint Medicines, Merck Sharp & Dohme, Hummingbird, and Yingli Pharma.

Dr Rodón also reported institutional grant/research support from AADi, Amgen, Bayer, Bicycle Therapeutics, BioAtla, BioMed Valley Discoveries, Cellestia Biotech, Curis, CytomX Therapeutics, Deciphera, Fore Biotherapeutics, Genmab, GlaxoSmithKline, Hutchison MediPharma, IDEAYA Biosciences, Kelun, Linnaeus Therapeutics, Loxo, Merus, Mirati Therapeutics, Novartis, Nuvation Bio, Pfizer, Roche, Spectrum Pharmaceuticals, Symphogen, Taiho Pharmaceutical, Takeda/Millennium, and Tango Therapeutics.


  1. Rodón J, Damian S, Furqan M, et al. Clinical and translational findings of pemigatinib in previously treated solid tumors with activating FGFR1-3 alterations in the FIGHT-207 study. Presented at: 2023 AACR Annual Meeting; April 14-19, 2023; Orlando, FL. Abstract CT016.
  2. Subbiah V, Iannotti NO, Gutierrez M, et al. 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. Ann Oncol. 2022;33(5):522-533. doi:10.1016/j.annonc.2022.02.001
  3. FDA approves pemigatinib for relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement. News release. FDA. August 26, 2022. Accessed April 18, 2023.
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