Derazantinib and Atezolizumab in Patients With Urothelial Cancer

NCT04045613 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: DZB-CS-2012019-000359-15
• Study Type: interventional
• Target: 95
• Locations: 13 countries
• Sites: 61

Brief Summary

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.

Conditions

Urothelial Carcinoma

Keywords

metastatic urothelial cancer; bladder cancer; Fibroblast Growth Factor Receptor; FGFR genetic aberration; targeted therapy; derazantinib; checkpoint inhibitor; immune checkpoint blockade; atezolizumab; Tecentriq; solid tumor

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5)

  ORR was defined as the proportion of patients who achieved a confirmed clinical response (CR) or partial response (PR) by blinded investigator central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST) Version 1.1

  From first dose up to 2 years

• Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2)

  The RP2D was determined by a joint decision taken by the Independent Data Monitoring Committee (IDMC), Investigators, and the Sponsor in reviewing the aggregate of DLT and AE data, and considering efficacy data

  From first dose up to 2 years

• Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2

  In Substudy 2, the primary endpoint was the number of patients with DLTs. A DLT was defined as a clinically-significant adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications. Any DLT had to be a toxicity considered at least possibly related to derazantinib or the combination of derazantinib and atezolizumab

  From first dose up to 2 years

Secondary Outcomes (6)

• Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies

  From first dose up to 2 years

• Duration of Response (DOR) Per RECIST 1.1

  From first dose up to 2 years

• ORR Based on RECIST 1.1 (Substudy 2)

  From first dose up to 2 years

• Progression-free Survival (PFS) by RECIST in All Substudies

  From first dose up to 2 years

• Overall Survival (OS) in All Substudies

  From first dose up to 2 years

Study Arms (7)

Substudy 1: Derazantinib 300 mg once daily

EXPERIMENTAL

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

Drug: Derazantinib 300 mg once daily monotherapy

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

EXPERIMENTAL

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

Drug: Derazantinib 200 mg once daily + atezolizumab 1200 mg

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

EXPERIMENTAL

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

Drug: Derazantinib 300 mg once daily+ atezolizumab 1200 mg

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

EXPERIMENTAL

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

Drug: Derazantinib 200 mg twice daily + atezolizumab 1200 mg

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

EXPERIMENTAL

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

Drug: Derazantinib 300 mg once daily monotherapy (QD)

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

EXPERIMENTAL

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

Drug: Derazantinib 300 mg once daily + atezolizumab 1200 mg

Substudy 5: Derazantinib 200 mg twice daily

EXPERIMENTAL

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

Drug: Derazantinib 200 mg twice daily monotherapy

Interventions

Derazantinib 300 mg once daily monotherapy DRUG

Derazantinib was administered orally at a dose of 300 mg once daily

Substudy 1: Derazantinib 300 mg once daily

Derazantinib 200 mg once daily + atezolizumab 1200 mg DRUG

Derazantinib was administered orally at a dose of 200 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

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

Derazantinib 300 mg once daily + atezolizumab 1200 mg DRUG

Derazantinib was administered orally at a dose of 300 mg once daily in combination with atezolizumab 1200 mg every 3 weeks

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

Derazantinib 200 mg twice daily + atezolizumab 1200 mg DRUG

Derazantinib was administered orally at a dose of 200 mg twice daily in combination with atezolizumab 1200 mg every 3 weeks

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

Derazantinib 300 mg once daily monotherapy (QD) DRUG

Derazantinib was administered orally at a dose of 300 mg once daily

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

Derazantinib 200 mg twice daily monotherapy DRUG

Derazantinib was administered orally at a dose of 200 mg twice daily

Substudy 5: Derazantinib 200 mg twice daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (66)

CTCA Clinical Research Inc., Atlanta

Newnan, Georgia, 30265, United States

Location

Englander Institute Weill Cornell Medicine

New York, New York, 10021, United States

Location

New York Cancer and Blood Specialists

Port Jefferson Station, New York, 11776, United States

Location

University of Texas Southwestern Medical Center (UTSWMC)

Dallas, Texas, 75390-8852, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Medical Oncology Associates PS (dba Summit Cancer Centers)

Spokane, Washington, 99208, United States

Location

Coastal Cancer Care

Birtinya, 4575, Australia

Location

Canberra Hospital and Health Services

Canberra, 2065, Australia

Location

John Flynn Private Hospital

Tugun, 4224, Australia

Location

Ballarat Oncology & Haematology Services

Wendouree, 3355, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Medizinische Universitaet Wien - Allgemeines Krankenhaus der Stadt Wien (AKH) - Universitaetsklinik fuer Urologie

Vienna, 1090, Austria

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Juravinski Cancer Center

Hamilton, L8V 5C2, Canada

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 61700, Czechia

Location

Fakultni Nemocnice Olomouc

Olomouc, 77900, Czechia

Location

Institut Bergonie

Bordeaux, 33076 CEDEX, France

Location

Centre François Baclesse

Caen, 14000, France

Location

CHU Timone / CEPCM

Marseille, 13005, France

Location

Medical Oncology - Pitié-Salpêtrière Hopital

Paris, 75030, France

Location

IUCT-Oncopole de Toulouse

Toulouse, 31100, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Campus Charite Mitte

Berlin, 10117, Germany

Location

Universitaetsklinikum Duesseldorf

Düsseldorf, 40225, Germany

Location

University Clinic Erlangen

Erlangen, 91054, Germany

Location

Universitaetsklinikum Magdeburg A.oe.R

Magdeburg, 39120, Germany

Location

Studienpraxis Urologie

Nürtingen, 72622, Germany

Location

National Institute of Oncology

Budapest, 1122, Hungary

Location

Bacs- Kiskun Megyei Korhaz

Kecskemét, 6000, Hungary

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

IRCCS - Istituto Europeo di Oncologia IEO

Milan, 20141, Italy

Location

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, 53100, Italy

Location

ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio

Sondrio, 23100, Italy

Location

Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego

Lublin, 20-718, Poland

Location

Med-Polonia Sp. z o. o.

Poznan, 60-693, Poland

Location

Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o., 04-073, Warszawa, Poland

Warsaw, 04-073, Poland

Location

Mazowiecki Szpital Onkologiczny

Wieliszew, 05-135, Poland

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Chungnam National University Hospital

Daejeon, 35105, South Korea

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Yonsei University Health System

Seoul, 3722, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

Seoul St. Marys Hospital Catholic University of Korea

Seoul, 6591, South Korea

Location

Vall d Hebron Hospital

Barcelona, 08035, Spain

Location

Hospital del Mar

Barcelona, 8003, Spain

Location

IOB - Hospital Quiron Salud

Barcelona, 8023, Spain

Location

ICO Hospitalet

Barcelona, 8908, Spain

Location

Hospital Universitario HM Sanchinarro CIOCC

Madrid, 28050, Spain

Location

Marques de Valdecilla University Hospital

Santander, 39011, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 14009, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Lausanne University Hospital

Lausanne, 1011, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, 8091, Switzerland

Location

Barts and The London School of Medicine and Dentistry - Barts Cancer Institute (BCI)

London, EC1M 6BQ, United Kingdom

Location

The Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

University College London Hospitals

London, W1T7HA, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Necchi A, Ramlau R, Falcon Gonzalez A, Chaudhry A, Todenhofer T, Tahbaz R, Fontana E, Giannatempo P, Deville JL, Pouessel D, Yoon S, Powles T, Bernat M, Hackl M, Marszewska M, McKernan P, Saulay M, Scaleia F, Engelhardt M, Loriot Y, Siefker-Radtke A, De Santis M. Derazantinib alone and with atezolizumab in metastatic urothelial carcinoma with activating FGFR aberrations. JNCI Cancer Spectr. 2024 Apr 30;8(3):pkae030. doi: 10.1093/jncics/pkae030.

  PMID: 38627238 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Acrocephalosyndactylia

Interventions

derazantinib; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Study Director
• Organization: Basilea Pharmaceutica International Ltd, Allschwil

manuel.haeckl@basilea.com

+41 76 302 53 10

Study Officials

• Manuel Häckl, MD

  Basilea Pharmaceutica International Ltd, Allschwil

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: August 5, 2019
• Study Start: August 2, 2019
• Primary Completion: October 4, 2022
• Study Completion: October 4, 2022
• Last Updated: October 13, 2023
• Results First Posted: October 13, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

HU (2); GB (4); FR (6); DE (5); AU (1); CZ (2); KR (11); CA (2); US (7); IT (6); PL (4); CH (3); ES (8)