Derazantinib and Atezolizumab in Patients With Urothelial Cancer

Overview

The purpose of this study is to evaluate efficacy of derazantinib single-agent or derazantinib-atezolizumab in combination in patients with advanced urothelial cancer harboring fibroblast growth factor receptor (FGFR) genetic aberrations (GA) of various clinical stages of disease progression and prior treatments.

Full Title of Study: “An Open-label Multi-cohort Phase 1b/2 Study of Derazantinib and Atezolizumab in Patients With Urothelial Cancer Expressing Activating Molecular FGFR Aberrations”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2022

Detailed Description

The study comprises four open-label substudies in patients with advanced urothelial cancer harboring FGFR GA who will be treated by single-agent derazantinib or derazantinib in combination with atezolizumab. The study enrolls patients with cisplatin-ineligible status, or patients whose disease progressed after either first-line treatment or prior treatment with FGFR inhibitors.

Interventions

  • Drug: Derazantinib
    • Substudy 1: Derazantinib will be administered orally at a dose of 300mg once per day Substudy 2: Derazantinib will be administered orally at various dose levels Substudy 3 and 4: Derazantinib will be administered orally at the dose of 300mg once per day as single agent or at the identified RP2D for derazantinib-atezolizumab
  • Drug: Atezolizumab (drug supplied by Hoffmann-La Roche)
    • Atezolizumab will be intravenously administered every 3 weeks at a dose of 1200mg.

Arms, Groups and Cohorts

  • Experimental: Derazantinib [Substudy 1]
    • Patients with urothelial cancer who have progressed on at least one line of standard treatment will be treated with derazantinib.
  • Experimental: Derazantinib + Atezolizumab: Dose finding [Substudy 2]
    • Dose finding and dose expansion in patients with solid tumor.
  • Experimental: Derazantinib +/- Atezolizumab: First line [Substudy 3]
    • Patients with urothelial cancer will be randomized for first-line treatment with either derazantinib alone or the recommended phase 2 dose (RP2D) for derazantinib-atezolizumab.
  • Experimental: Derazantinib +/- Atezolizumab: Second line [Substudy 4]
    • Patients with urothelial cancer progressing after prior FGFR inhibitor treatment will be randomized to receive either derazantinib alone or the RP2D for derazantinib-atezolizumab.

Clinical Trial Outcome Measures

Primary Measures

  • Overall Response Rate (ORR) based on RECIST 1.1
    • Time Frame: Approximately up to 2 years
  • Recommended Phase 2 dose (RP2D) of derazantinib in combination with atezolizumab
    • Time Frame: Approximately up to 8 weeks

Secondary Measures

  • Disease control rate per RECIST 1.1
    • Time Frame: Approximately up to 2 years
  • Duration of Response per RECIST 1.1
    • Time Frame: Approximately up to 2 years
  • Median progression-free survival (PFS) and PFS at 6 months
    • Time Frame: Approximately up to 2 years
  • Median overall survival (OS) and OS at 6 months
    • Time Frame: Approximately up to 2 years
  • Safety and tolerability of study treatment based on incidence of treatment-emergent adverse events
    • Time Frame: Approximately up to 2 years

Participating in This Clinical Trial

Inclusion Criteria

  • Histologically-confirmed transitional cell carcinoma of the urothelium of the upper or lower urinary tract – Recurrent or progressing stage IV disease, or surgically unresectable, recurrent or progressing disease – Documented central FGFR genetic alteration – Measurable disease per RECIST 1.1 – Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 – Adequate bone marrow, liver and renal function Exclusion Criteria:
  • Receipt of chemotherapy, targeted therapies, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or at least 5 half-lives of the drug whichever is longer before the first dose of study drug. – Concurrent evidence of any clinically significant corneal or retinal disorder – Phosphatemia greater than institutional upper limit of normal (ULN) at screening – Uncontrolled tumor-related hypercalcemia
  • Gender Eligibility: All

    Minimum Age: 18 Years

    Maximum Age: N/A

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Basilea Pharmaceutica
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Frédérique Cantero, MD, Study Director, Basilea Pharmaceutica International Ltd
    • Overall Contact(s)
      • Frédérique Cantero, MD, +41 76 830 2499, Frederique.Cantero@basilea.com

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