FDA Approves Infigratinib for FGFR2+ Cholangiocarcinoma


The FDA has approved infigratinib for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.


The FDA has approved infigratinib (Truseltiq) for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.1

The application for infigratinib was evaluated under the FDA's Real-Time Oncology Review pilot program, which was developed to expedite the distribution of safe and effective therapies to patients with cancer.

The regulatory decision was based on data from a phase 2 trial (NCT02150967) of 108 patients who had undergone at least 1 previous treatment for advanced cholangiocarcinoma. The agent elicited a confirmed objective response rate (ORR) of 23% (95% CI, 16%-32%), and the median duration of response (DOR) was 5.0 months (95% CI, 3.7-9.3 months).2

“This is an important milestone for patients diagnosed with FGFR2-fusion-driven cholangiocarcinoma who have recurred after first-line therapy and are in need of targeted options for further treatment,” Susan Moran, MD, MSCE, chief medical officer for QED Therapeutics, Inc, stated in a press release. “Based on the efficacy seen to date, our team believes infigratinib possesses promise for a range of FGFR-driven conditions, including other cancers. We will continue to evaluate its safety and efficacy in these areas of unmet need.”

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.

The open-label phase 2 trial enrolled patients with unresectable locally advanced or metastatic cholangiocarcinoma who had progressed on, or were intolerant to, gemcitabine-based chemotherapy. To be eligible for enrollment on the trial, patients had to have tumors that harbored FGFR gene fusions or rearrangements.

The trial is comprised of 3 cohorts: those with FGFR2 gene fusions/rearrangements (cohort 1; n = 120), those with FGFR1&3 gene fusions/rearrangements and/or FGFR mutations (cohort 2; n = 20), and those with FGFR2 gene fusions who have progressed after previous treatment with a selective FGFR inhibitor other than infigratinib (cohort 3; n = 20).

Study participants were given single-agent infigratinib at a dose of 125 mg once day for 21 days every 28-day treatment cycle.

The co-primary end points of the trial were ORR and DOR, while key secondary end points comprised progression-free survival (PFS), disease control rate (DCR), best ORR, overall survival, safety, and pharmacokinetics.

The median age of participants at baseline was 53 years (range, 23-81), 62.0% were female, 72.2% were White, and 57.4% had an ECOG performance status of 1. The majority of the patients (99.1%) had stage IV disease at study entry. About 26% of patients had non-liver metastasis in the bone, 68.5% had it in the lung, 57.4% had it in the nodes, and 38.0% had it in another site.

Moreover, patients received a median of 2 prior lines of treatment; 46.3% received 0 or 1 prior lines, 29.6% received 2 prior lines, 13.0% received 3 prior lines, and 11.1% received 4 or more prior lines of therapy.

Additional data presented during the 2021 Gastrointestinal Cancers Symposium indicated that of those who responded to infigratinib, 1 experienced a complete response, 24 had a partial response, and 66 achieved disease stability; 11 patients experienced disease progression and 6 had unknown status.

Per blinded independent central review, best ORR rate with infigratinib was 34.3% (95% CI, 25.4%-44.0%), and the median time to response was 3.6 months. Moreover, the disease control rate achieved with the agent was 84.3% (95% CI, 76.0%-90.6%).

Additionally, patients who received infigratinib experienced a median PFS of 7.3 months (95% CI, 5.6-7.6), with a 4-month PFS rate of 75.2%. The median OS in these patients was 12.2 months (95% CI, 10.7-14.9).

Per investigator assessment, infigratinib elicited a confirmed ORR of 30.6% (95% CI, 22.1%-40.2%), with a median DOR of 6.0 months (95% CI, 5.2-9.0).

When looking at efficacy with infigratinib based on prior lines of therapy received, findings indicated that among those who had received 0 to 1 previous lines of treatment (n = 50), the confirmed ORR with the agent was 34.0% (95% CI, 21.2%-48.8%), with a best ORR rate of 42.0% (95% CI, 28.2%-56.8%) and a DCR of 88.0% (95% CI, 75.7%-95.5%).

Among those who had received 2 or more prior lines of treatment, infigratinib elicited a confirmed ORR of 13.8% (95% CI, 6.1%-25.4%), with a best ORR of 27.6% (95% CI, 16.7%-40.9%), and a DCR of 81.0% (95% CI, 68.6%-90.1%).

Previous 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 PFS and ORR when given as a third- and later-line treatment for patients with FGFR2 fusion–positive cholangiocarcinoma.3

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.4 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.

Common toxicities experienced with infigratinib include increased creatinine, increased phosphate, decreased phosphate, nail toxicity, stomatitis, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, dry eye, fatigue, increased lipase, decreased lymphocytes, increased calcium, decreased sodium, alopecia, increased triglycerides, increased aspartate aminotransferase, decreased platelets, increased urate, palmar-plantar erythrodysesthesia syndrome, arthralgia, and dysgeusia.

"While targeted treatments have extended survival for many types of cancer, people diagnosed with cholangiocarcinoma have previously been presented with extremely limited treatment options coupled with low statistical survival data,” Milind Javle, MD, professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, stated in a press release. “In this study, [infigratinib] showed promise as a targeted treatment option for patients with FGFR2 fusion–driven cholangiocarcinoma with a well-tolerated safety profile in line with previous observations in this patient population.”


  1. Bridgebio pharma’s affiliate qed therapeutics and partner helsinn group announce fda approval of truseltiq (infigratinib) for patients with cholangiocarcinoma. News release. BridgeBio Pharma, Inc. May 28, 2021. Accessed May 28, 2021. https://bit.ly/3wE320C
  2. Javle M, Roychowdhury S, Kelley RK, et al. Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. J Clin Oncol. 2021;39(suppl 3):265. doi:10.1200/JCO.2021.39.3_suppl.265
  3. 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.
  4. 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
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