Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Standard of Care for Urothelial Carcinoma (FIGHT-205)
Condition: Metastatic Urothelial Carcinoma; Unresectable Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Pemigatinib; Pembrolizumab; Gemcitabine; Carboplatin
Intervention description: 13.5 mg once a day orally; 200 mg Q3W intravenously; 1000 mg/m^2 IV over 30 minutes on Days 1 and 8 of each 3-week cycle; Dosed to target AUC of 5 mg/mL/min or 4.5 mg/mL/min if required per local guidelines on Day 1 or 2 of each 3-week cycle
Intervention MeSH terms: Carboplatin; Gemcitabine; Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urothelial carcinoma; fibroblast growth factor receptor (FGFR) inhibitor; FGFR3 mutation; FGFR3 rearrangement; metastatic; unresectable; cisplatin-ineligible

Summary:

      The purpose of this study is to evaluate the safety and efficacy of pemigatinib plus
      pembrolizumab or pemigatinib alone versus the standard of care for participants with
      metastatic or unresectable urothelial carcinoma who are not eligible to receive cisplatin,
      are harboring FGFR3 mutation or rearrangement, and who have not received prior treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically documented metastatic or unresectable urothelial carcinoma. Both
             transitional cell and mixed transitional cell histologies are allowed, provided
             urothelial component is ≥ 50%.

          -  At least 1 measurable target lesion per RECIST v1.1.

          -  Must be ineligible to receive cisplatin. Patients ineligible for any platinum-based
             chemotherapy are allowed.

          -  Known FGFR3 mutation or rearrangement confirmed by the central laboratory prior to
             randomization.

          -  Central laboratory test result of PD-L1 status is mandatory at screening.

          -  Have received no prior systemic chemotherapy for metastatic or unresectable urothelial
             carcinoma (except adjuvant platinum-based chemotherapy following radical cystectomy,
             with recurrence > 12 months from completion of therapy, or neo-adjuvant platinum-based
             chemotherapy, with recurrence > 12 months since completion of therapy).

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

          -  Willingness to avoid pregnancy or fathering children.

        Exclusion Criteria:

          -  Prior receipt of a selective FGFR inhibitor for any indication or reason.

          -  Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent
             directed to another co-inhibitory T-cell receptor.

          -  Receipt of anticancer medications or investigational drugs for unresectable and/or
             metastatic disease.

          -  Concurrent anticancer therapy, except for treatment allowed per protocol.

          -  Has disease that is suitable for local therapy administered with curative intent.

          -  Has tumor with any neuroendocrine or small cell component.

          -  Current evidence of clinically significant corneal or retinal disorder as confirmed by
             ophthalmologic examination.

          -  Has received prior radiotherapy to a metastatic site without the use of chemotherapy
             radiosensitization within 3 weeks of the first dose of study treatment, with the
             exception of palliative radiotherapy to bone lesions, which is allowed if completed 2
             weeks before the start of study treatment.

          -  Has central nervous system metastases, unless the participant has completed local
             therapy (eg, whole brain radiation therapy, surgery, radiosurgery) and has
             discontinued use of corticosteroids for this indication for at least 4 weeks before
             starting treatment in this study.

          -  Known additional malignancy that is progressing or required active treatment within
             the past 3 years

          -  Laboratory values outside the protocol-defined range at screening.

          -  Clinically significant or uncontrolled cardiac disease.

          -  History of autoimmune disease that has required systemic treatment in past 2 years.