Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Standard of Care for Urothelial Carcinoma (FIGHT-205)

A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Plus Pembrolizumab Versus Pemigatinib Alone Versus Standard of Care as First-Line Treatment for Metastatic or Unresectable Urothelial Carcinoma in Cisplatin-Ineligible Participants Whose Tumors Express FGFR3 Mutation or Rearrangement (FIGHT-205)

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.

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.