FDA Grants Priority Review to Infigratinib for Cholangiocarcinoma

The FDA has granted a priority review designation to the oral FGFR1-3 selective inhibitor infigratinib for the treatment of patients with cholangiocarcinoma, according to an announcement from BridgeBio Pharma, Inc.¹

The new drug application for the agent is being assessed under the Real-Time Oncology Review pilot program, which was developed to expedite the distribution of safe and effective therapies to patients with cancer.

The pharmaceutical company announced plans to submit the application for review in Australia and Canada under Project Orbis, which permits concurrent submission and review of cancer therapies among participating international regulatory agencies.

“We want to thank the patients, families, scientists, physicians and all others involved who helped us move this NDA forward,” Neil Kumar, PhD, CEO of BridgeBio, stated in a press release. “At BridgeBio, we believe that every minute counts for patients and their families, and we are eager to help as many people suffering from cholangiocarcinoma as possible—as quickly as possible.”

An oral agent, infigratinib is an ATP-competitive, FGFR1-3 TKI that is under investigation for patients whose tumors harbor FGFR mutations, including those with cholangiocarcinoma, urothelial carcinoma, and achondroplasia.

Results from a retrospective analysis presented during the 2020 ASCO Virtual Scientific Program and the 2020 ESMO World Congress on Gastrointestinal Cancer demonstrated that infigratinib induced a clinically meaningful progression-free survival (PFS) and overall response rate (ORR) when given as a third- and later-line treatment for patients with FGFR2 fusion–positive cholangiocarcinoma.²

Infigratinib resulted in a median PFS of 6.77 months (95% CI, 3.94-7.79) compared with 4.63 months (95% CI, 2.69-7.16) with pre-infigratinib, second-line chemotherapy. The ORR with the agent was 21.6% (95% CI, 9.8-38.2) versus just 5.4% (95% CI, 0.7-18.2) with second-line chemotherapy.

In the analysis, investigators evaluated data from a subset of 37 patients with FGFR-mutant advanced or metastatic cholangiocarcinoma who had been administered second-line chemotherapy and subsequent third- or later-line infigratinib as part of a single-arm phase 2 trial (NCT02150967).

The effectiveness of each intervention was compared in the subset of patients to define outcomes for patients with FGFR2-mutated cholangiocarcinoma who received standard chemotherapy in the second-line setting. Before this investigation, this had been largely unknown.³ Standard chemotherapy for this population has historically been comprised of gemcitabine- or capecitabine-based combinations, and leucovorin calcium, fluorouracil, oxaliplatin (FOLFOX).

Overall, the study had enrolled a total of 71 patients with advanced or metastatic cholangiocarcinoma that harbored either FGFR2 fusions or other FGFR alterations; these patients had progressed on previous treatment.

In the patient subset, 38% (n = 14) of patients were male, while 62% (n = 23) were female. Moreover, 76% (n = 28) were white, 5% (n = 2) were Black/African American, 5% (n = 2) were Asian, and 14% (n = 5) were other race or did not have those data available. More than half, or 57% (n = 21) of patients had an ECOG performance status of 1, while 43% (n = 16) had a status of 0. Additionally, all patients had received 2 or more previous therapies, and all had FGFR2 positivity.

In the trial, participants were given infigratinib at a once-daily dose of 125 mg for 21 days, followed by 7 days off therapy, for 28-day treatment cycles. Treatment was continued until either intolerable toxicity, progressive disease, cessation per investigation discretion, or withdrawn consent from the patient. The primary end point of the trial was ORR per investigator assessment.⁴

Data presented at the 2019 ESMO World Congress on Gastrointestinal Cancer showed that infigratinib elicited an ORR of 31.0% (95% CI, 20.5-43.1), with no complete responses, a 25.4% partial response rate (n = 18) and a 57.7% (n = 41) stable disease rate. Of those with the potential for confirmation, defined as patients who completed 6 cycles of treatment or discontinued before the sixth cycle, the median PFS was 6.8 months (95% CI, 5.3-7.6). Here, the median duration of response was 5.4 months (95% CI, 3.7-7.4) and the median overall survival (OS) was 12.5 months (95% CI, 9.9-16.6).

References

1. BridgeBio Pharma and affiliate QED Therapeutics announce FDA acceptance of new drug application for infigratinib for the treatment of cholangiocarcinoma. News release. December 1, 2020. Accessed December 1, 2020. https://bit.ly/36oTe04.
2. Javle M, Sadeghi , Roychowdhury S, et al. Efficacy of second-line chemotherapy in patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions: a retrospective analysis. Presented at: ESMO World Congress on Gastrointestinal Cancer 2020. July 1-4, 2020; Virtual. ASO-5.
3. Outcomes from second-line chemotherapy in patients with cholangiocarcinoma and FGFR2 fusions. News release. European Society for Medical Oncology. July 1, 2020. Accessed December 1, 2020. https://bit.ly/38pnl6U
4. Javle M, Kelley RK, Roychowdhoury S, et al. A phase II study of infigratinib (BGJ398) in previously-treated advanced cholangiocarcinoma containing FGFR2 fusions. Presented at: Cholangiocarcinoma Foundation Annual Conference 2019. January 30-February 2, 2019. https://bit.ly/2NRezpa