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NCT04045613: FIDES-02

Derazantinib and Atezolizumab in Patients With Urothelial Cancer

Completed Phase 1, PHASE2 Results posted Last updated 13 October 2023
What this trial tests

Phase 1, PHASE2 trial testing Derazantinib 300 mg once daily monotherapy in Urothelial Carcinoma in 95 participants. Completed in 4 October 2022.

Timeline
2 August 2019
Primary endpoint
4 October 2022
4 October 2022

Quick facts

Lead sponsorBasilea Pharmaceutica
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment95
Start date2 August 2019
Primary completion4 October 2022
Estimated completion4 October 2022
Sites66 locations across France, Italy, Austria, United Kingdom, Germany, Hungary, Poland, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Basilea Pharmaceutica — full company profile →

Who can join

18 and older, any sex, with Urothelial Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Based on RECIST 1.1 (Substudies 1,3,4 and 5) Primary · From first dose up to 2 years

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

GroupValue95% CI
Substudy 1: Derazantinib 300 mg Once Daily9.42.0 – 25.0
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg0.00.0 – 84.2
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily14.30.4 – 57.9
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg0.00.0 – 30.8
Substudy 5: Derazantinib 200 mg Twice Daily5.90.1 – 28.7
Recommended Phase 2 Dose (RP2D) of Derazantinib-atezolizumab in Combination Based on DLT Criteria, Safety and Efficacy Data (Substudy 2) Primary · From first dose up to 2 years

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

GroupValue95% CI
Substudy 2 Combined (Dose-Level 1 and 2): Derazantinib 200 or 300 Once Daily+ Atezolizumab 1200 mg300
Number of Patients With Dose-limiting Toxicities (DLTs) in Substudy 2 Primary · From first dose up to 2 years

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

GroupValue95% CI
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily + Atezolizumab 1200 mg0
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg0
Disease Control Rate (DCR) Per RECIST 1.1 in All Substudies Secondary · From first dose up to 2 years

DCR was defined as the proportion of patients who achieved a confirmed clinical response (CR), partial response (PR) or stable disease (SD) by BICR using the internationally recognized criteria in accordance with RECIST Version 1.1

GroupValue95% CI
Substudy 1: Derazantinib 300 mg Once Daily18.87.2 – 36.4
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily + Atezolizumab 1200 mg18.22.3 – 51.8
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg50.021.1 – 78.9
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg50.01.3 – 98.7
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily28.63.7 – 71.0
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg20.02.5 – 55.6
Substudy 5: Derazantinib 200 mg Twice Daily52.927.8 – 77.0
Duration of Response (DOR) Per RECIST 1.1 Secondary · From first dose up to 2 years

DOR was calculated from the first date of documented tumor response (confirmed CR or PR) to the date of disease progression as assessed by BICR or death per RECIST 1.1

GroupValue95% CI
Substudy 1: Derazantinib 300 mg Once Daily6.9NA – NA
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily+ Atezolizumab 1200 mgNANA – NA
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily+ Atezolizumab 1200 mg7.46.9 – 7.9
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mgNANA – NA
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily3.3NA – NA
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mgNANA – NA
Substudy 5: Derazantinib 200 mg Twice DailyNANA – NA
ORR Based on RECIST 1.1 (Substudy 2) Secondary · From first dose up to 2 years

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

GroupValue95% CI
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily + Atezolizumab 1200 mg0.00.0 – 28.5
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg16.72.1 – 48.4
Progression-free Survival (PFS) by RECIST in All Substudies Secondary · From first dose up to 2 years

PFS was calculated as the time from cohort assignment until disease progression as assessed by BICR, or death from any cause, whichever came first

GroupValue95% CI
Substudy 1: Derazantinib 300 mg Once Daily2.01.9 – 2.1
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily + Atezolizumab 1200 mg2.01.5 – 2.1
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily+ Atezolizumab 1200 mg4.20.7 – 10.8
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg2.50.6 – 4.4
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily2.00.6 – 4.7
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg1.90.2 – 4.1
Substudy 5: Derazantinib 200 mg Twice Daily2.12.1 – 7.0
Overall Survival (OS) in All Substudies Secondary · From first dose up to 2 years

OS was calculated from the date of cohort assignment until death from any cause

GroupValue95% CI
Substudy 1: Derazantinib 300 mg Once Daily4.73.4 – 7.3
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily + Atezolizumab 1200 mg8.73.0 – NA
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily+ Atezolizumab 1200 mg12.62.5 – NA
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg4.22.3 – 6.2
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once DailyNA2.3 – NA
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg6.21.1 – 11.8
Substudy 5: Derazantinib 200 mg Twice Daily7.55.6 – 9.0
Number of Patients With at Least Grade 3 Adverse Events (AEs) Secondary · From first dose and until 90 days following the last dose

Common Terminology Criteria for Adverse Events (CTCAE) displayed by increasing severity grades 3 to 5 (CTCAE grade 3/4/5 )

GroupValue95% CI
Substudy 1: Derazantinib 300 mg Once Daily11
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily+ Atezolizumab 1200 mg5
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg7
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg0
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily2
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg5
Substudy 5: Derazantinib 200 mg Twice Daily3
Substudy 1: Derazantinib 300 mg Once Daily11
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily+ Atezolizumab 1200 mg3
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg3
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg2
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily2
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg4
Substudy 5: Derazantinib 200 mg Twice Daily9
Substudy 1: Derazantinib 300 mg Once Daily10
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily+ Atezolizumab 1200 mg6
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg2
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg0
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily4
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg1
Substudy 5: Derazantinib 200 mg Twice Daily5

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs were assessed from first dose and until 90 days following the last dose. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Substudy 1: Derazantinib 300 mg Once Daily
Serious: 17/32 (53%)
Deaths: 8/32
Substudy 2 (Dose-Level 1): Derazantinib 200 mg Once Daily + Atezolizumab 1200 mg
Serious: 4/14 (29%)
Deaths: 3/14
Substudy 2 (Dose-Level 2): Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg
Serious: 6/12 (50%)
Deaths: 3/12
Substudy 3: Derazantinib 200 mg Twice Daily + Atezolizumab 1200 mg
Serious: 1/2 (50%)
Deaths: 1/2
Substudy 4 (Cohort 4a):Derazantinib 300 mg Once Daily
Serious: 3/8 (38%)
Deaths: 0/8
Substudy 4 (Cohort 4b):Derazantinib 300 mg Once Daily + Atezolizumab 1200 mg
Serious: 6/10 (60%)
Deaths: 4/10
Substudy 5: Derazantinib 200 mg Twice Daily
Serious: 8/17 (47%)
Deaths: 1/17

Serious adverse events (58 terms)

ReactionSystemSubstudy 1: Derazantinib 3…Substudy 2 (Dose-Level 1):…Substudy 2 (Dose-Level 2):…Substudy 3: Derazantinib 2…Substudy 4 (Cohort 4a):Der…Substudy 4 (Cohort 4b):Der…Substudy 5: Derazantinib 2…
Disease progressionGeneral disorders
VomitingGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Eastern Cooperative Oncology Group performance status worsenedInvestigations
AnaemiaBlood and lymphatic system disorders
Acute kidney injuryRenal and urinary disorders
FatigueGeneral disorders
Blood creatine phosphokinase increasedInvestigations
Blood creatinine increasedInvestigations
Acute myocardial infarctionCardiac disorders
BradycardiaCardiac disorders
Sinus bradycardiaCardiac disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Gastric haemorrhageGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Intestinal perforationGastrointestinal disorders
NauseaGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
HaematuriaRenal and urinary disorders
Other adverse events (97 terms — click to expand)

ReactionSystemSubstudy 1: Derazantinib 3…Substudy 2 (Dose-Level 1):…Substudy 2 (Dose-Level 2):…Substudy 3: Derazantinib 2…Substudy 4 (Cohort 4a):Der…Substudy 4 (Cohort 4b):Der…Substudy 5: Derazantinib 2…
NauseaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
ConstipationGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
AstheniaGeneral disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Dry mouthGastrointestinal disorders
Blood creatinine increasedInvestigations
VomitingGastrointestinal disorders
Amylase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Blood phosphorus increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Lipase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
DehydrationMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Weight decreasedInvestigations
LymphopeniaBlood and lymphatic system disorders
DysgeusiaNervous system disorders
Dry eyeEye disorders
Vision blurredEye disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HypercalcaemiaMetabolism and nutrition disorders
HyperphosphataemiaMetabolism and nutrition disorders
Urinary tract infectionInfections and infestations
HypertensionVascular disorders
PyrexiaGeneral disorders
Blood creatine phosphokinase increasedInvestigations
Blood thyroid stimulating hormone increasedInvestigations
C-reactive protein increasedInvestigations
Haemoglobin decreasedInvestigations
Platelet count decreasedInvestigations
Transaminases increasedInvestigations
TremorNervous system disorders

Most-reported serious reactions: Disease progression, Vomiting, Alanine aminotransferase increased, Aspartate aminotransferase increased, Eastern Cooperative Oncology Group performance status worsened, Anaemia, Acute kidney injury, Fatigue.

Data from ClinicalTrials.gov NCT04045613 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice.
    Kommalapati A, Tella SH, Borad M, Javle M, et al · · 2021 · cited 119× · PMID 34199304 · DOI 10.3390/cancers13122968
  2. FGFR Fusions in Cancer: From Diagnostic Approaches to Therapeutic Intervention.
    De Luca A, Esposito Abate R, Rachiglio AM, Maiello MR, et al · · 2020 · cited 87× · PMID 32962091 · DOI 10.3390/ijms21186856
  3. Unleashing the potential of combining FGFR inhibitor and immune checkpoint blockade for FGF/FGFR signaling in tumor microenvironment.
    Ruan R, Li L, Li X, Huang C, et al · · 2023 · cited 86× · PMID 36966334 · DOI 10.1186/s12943-023-01761-7
  4. Targeted therapies for advanced bladder cancer: new strategies with FGFR inhibitors.
    Casadei C, Dizman N, Schepisi G, Cursano MC, et al · · 2019 · cited 76× · PMID 31803255 · DOI 10.1177/1758835919890285
  5. Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma.
    Mollica V, Rizzo A, Montironi R, Cheng L, et al · · 2020 · cited 75× · PMID 32498352 · DOI 10.3390/cancers12061449
  6. Tyrosine Kinase Receptors in Oncology.
    Esteban-Villarrubia J, Soto-Castillo JJ, Pozas J, San Román-Gil M, et al · · 2020 · cited 72× · PMID 33198314 · DOI 10.3390/ijms21228529
  7. <i>FGFR3</i> Alterations in the Era of Immunotherapy for Urothelial Bladder Cancer.
    Kacew A, Sweis RF. · · 2020 · cited 51× · PMID 33224141 · DOI 10.3389/fimmu.2020.575258
  8. Fibroblast growth factor receptor fusions in cancer: opportunities and challenges.
    Chen L, Zhang Y, Yin L, Cai B, et al · · 2021 · cited 50× · PMID 34732230 · DOI 10.1186/s13046-021-02156-6

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing