Derazantinib and Atezolizumab in Patients With Urothelial Cancer (FIDES-02)

Basilea Pharmaceutica

Status and phase: Completed; Phase 2; Phase 1

Conditions: Urothelial Carcinoma

Treatments: Drug: Derazantinib 200 mg once daily + atezolizumab 1200 mg; Drug: Derazantinib 200 mg twice daily + atezolizumab 1200 mg; Drug: Derazantinib 300 mg once daily monotherapy; Drug: Derazantinib 300 mg once daily monotherapy (QD); Drug: Derazantinib 300 mg once daily+ atezolizumab 1200 mg; Drug: Derazantinib 300 mg once daily + atezolizumab 1200 mg; Drug: Derazantinib 200 mg twice daily monotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT04045613

2019-000359-15 (EudraCT Number)

DZB-CS-201

Details and patient eligibility

About

The purpose of this study was to evaluate efficacy of derazantinib monotherapy 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 description

The study comprised five open-label substudies (1-5) in patients with advanced urothelial cancer harboring FGFR GA (with the exception of substudy 2 which did not require a FGFR GA) who were treated by derazantinib monotherapy or derazantinib in combination with atezolizumab. The study enrolled patients with cisplatin-ineligible status, or patients whose disease progressed after either first-line treatment or prior treatment with FGFR inhibitors.

Enrollment: 95 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 aberration (FGFR1, FGFR2, or FGFR3 mutations / short variants and rearrangements / fusions) (Note; Substudy 2 started with patients requiring an FGFR GA, but this requirement was removed from the protocol later on)
• Measurable disease, as defined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• Adequate organ functions as indicated by Screening visit local laboratory values

Exclusion criteria

• Receipt of prior cancer treatment within specific interval periods
• Concurrent evidence of any clinically significant corneal or retinal disorder
• History of clinically significant cardiac disorders
• Known CNS metastases
• Concurrent uncontrolled or active infection with human immunodeficiency virus
• Active hepatitis B or chronic hepatitis B without current antiviral therapy
• Active hepatitis C
• Active tuberculosis
• Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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95 participants in 7 patient groups

Substudy 1: Derazantinib 300 mg once daily

Experimental group

Description:

Patients with urothelial cancer were treated with derazantinib 300 mg once daily

Treatment:

Drug: Derazantinib 300 mg once daily monotherapy

Substudy 2 (Dose-Level 1): Derazantinib 200 mg once daily + atezolizumab 1200 mg

Experimental group

Description:

Patients with any solid tumors were treated with derazantinib 200 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as intravenous (IV) infusion

Treatment:

Drug: Derazantinib 200 mg once daily + atezolizumab 1200 mg

Substudy 2 (Dose-Level 2): Derazantinib 300 mg once daily + atezolizumab 1200 mg

Experimental group

Description:

Patients with any solid tumors were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Treatment:

Drug: Derazantinib 300 mg once daily+ atezolizumab 1200 mg

Substudy 3: Derazantinib 200 mg twice daily + atezolizumab 1200 mg

Experimental group

Description:

Patients with urothelial cancer were treated with derazantinib 200 mg twice daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Treatment:

Drug: Derazantinib 200 mg twice daily + atezolizumab 1200 mg

Substudy 4 (Cohort 4a):Derazantinib 300 mg once daily

Experimental group

Description:

Patients with FGFR inhibitor resistant urothelial cancer were treated with derazantinib 300 mg once daily

Treatment:

Drug: Derazantinib 300 mg once daily monotherapy (QD)

Substudy 4 (Cohort 4b):Derazantinib 300 mg once daily + atezolizumab 1200 mg

Experimental group

Description:

Patients with urothelial cancer were treated with derazantinib 300 mg once daily in combination with atezolizumab 1200 mg given every 3 weeks as IV infusion

Treatment:

Drug: Derazantinib 300 mg once daily + atezolizumab 1200 mg

Substudy 5: Derazantinib 200 mg twice daily

Experimental group

Description:

Patients with urothelial cancer were treated with derazantinib 200 mg twice daily

Treatment:

Drug: Derazantinib 200 mg twice daily monotherapy