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NCT03834220

Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial)

Terminated Phase 2 Results posted Last updated 7 February 2024
What this trial tests

Phase 2 trial testing Debio 1347 in Solid Tumor in 63 participants. Terminated before completion.

Timeline
22 March 2019
Primary endpoint
31 December 2020
4 January 2022

Quick facts

Lead sponsorDebiopharm International SA
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment63
Start date22 March 2019
Primary completion31 December 2020
Estimated completion4 January 2022
Sites105 locations across Finland, Taiwan, Poland, South Korea, Philippines, Croatia, Denmark, Netherlands

Drugs / interventions tested

Conditions studied

Sponsor

Debiopharm International SA — full company profile →

Who can join

18 and older, any sex, with Solid Tumor. 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) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria Primary · Up to disease progression or end of study (up to 1 year and 9 months)

ORR was defined as the percentage of participants with a best overall response (BOR) of partial or complete response (PR or CR). BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

GroupValue95% CI
Cohort 1: Debio 1347 (Biliary Tract Cancer)6.71.2 – 19.5
Cohort 2: Debio 1347 (Urothelial Cancer)00.0 – 63.2
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)4.00.2 – 17.6
Duration of Response (DOR) as Centrally Measured by Independent Review Committee (IRC) Secondary · Up to disease progression or end of study (up to 2 years and 9 months)

DOR was defined as the time from the date of the initial PR or CR to date of the first documented progression or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

GroupValue95% CI
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)5.55NA – NA
Disease Control Rate (DCR) as Centrally Measured by Independent Review Committee (IRC) Secondary · Up to disease progression or end of study (up to 2 years and 9 months)

DCR was defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or stable disease (SD) ≥6 weeks. BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor

GroupValue95% CI
Cohort 1: Debio 1347 (Biliary Tract Cancer)63.343.9 – 80.1
Cohort 2: Debio 1347 (Urothelial Cancer)00 – 60.2
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)34.517.9 – 54.3
Progression-Free Survival (PFS) as Centrally Measured by Independent Review Committee (IRC) Secondary · From the start of the study up to disease progression or death (up to 2 years and 9 months)

PFS was defined as the time from the start date of treatment to date of the first documented progression or death due to any cause.

GroupValue95% CI
Cohort 1: Debio 1347 (Biliary Tract Cancer)3.683.55 – 10.58
Cohort 2: Debio 1347 (Urothelial Cancer)1.770.95 – NA
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)1.841.71 – 3.52
Overall Survival (OS) Secondary · Until death or loss to follow-up or end of study (up to 2 years and 9 months)

OS was defined as the time from the start date of treatment to date of death due to any cause. Participants with no documented death were censored at the last date known to be alive.

GroupValue95% CI
Cohort 1: Debio 1347 (Biliary Tract Cancer)NANA – NA
Cohort 2: Debio 1347 (Urothelial Cancer)NANA – NA
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)7.134.30 – 11.37
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs) Secondary · From first dose of study drug up to 30 days post last dose (Up to 2 years and 9 months)

An AE is any untoward medical occurrence in a participant or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE that either starts or worsens in severity on or after the first administration of the study drug and within 30 days of the last administration of the study drug. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or signific

TEAEs
GroupValue95% CI
Cohort 1: Debio 1347 (Biliary Tract Cancer)30
Cohort 2: Debio 1347 (Urothelial Cancer)4
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)28
Serious TEAEs
GroupValue95% CI
Cohort 1: Debio 1347 (Biliary Tract Cancer)14
Cohort 2: Debio 1347 (Urothelial Cancer)2
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)7
Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma Secondary · Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days)

Geometric mean and geometric percent CV summary was estimated based on log-linear model.

GroupValue95% CI
Cohort 1: Debio 1347 (Biliary Tract Cancer)619.6± 100.0
Cohort 2: Debio 1347 (Urothelial Cancer)306.8± 43.4
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)463.2± 127.3
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma Secondary · Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days)

Geometric mean and geometric percent CV summary was estimated based on log-linear model.

GroupValue95% CI
Cohort 1: Debio 1347 (Biliary Tract Cancer)23326.7± 70.4
Cohort 2: Debio 1347 (Urothelial Cancer)13999.0± 39.1
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)18192.1± 86.2

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to 30 days post last dose (up to 2 years and 9 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Debio 1347 (Biliary Tract Cancer)
Serious: 14/30 (47%)
Deaths: 9/30
Cohort 2: Debio 1347 (Urothelial Cancer)
Serious: 2/4 (50%)
Deaths: 1/4
Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
Serious: 7/29 (24%)
Deaths: 17/29

Serious adverse events (31 terms)

ReactionSystemCohort 1: Debio 1347 (Bili…Cohort 2: Debio 1347 (Urot…Cohort 3: Debio 1347 (All …
Acute kidney injuryRenal and urinary disorders
PyrexiaGeneral disorders
Biliary sepsisInfections and infestations
Biliary tract infectionInfections and infestations
DehydrationMetabolism and nutrition disorders
Malignant melanomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
HypotensionVascular disorders
Oedema peripheralGeneral disorders
Laryngeal haemorrhageRespiratory, thoracic and mediastinal disorders
Blood creatinine increasedInvestigations
Femur fractureInjury, poisoning and procedural complications
Cardiac arrestCardiac disorders
SyncopeNervous system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
EnterocolitisGastrointestinal disorders
Gastric ulcerGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
CholelithiasisHepatobiliary disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Urinary tract obstructionRenal and urinary disorders
Back painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Other adverse events (95 terms — click to expand)

ReactionSystemCohort 1: Debio 1347 (Bili…Cohort 2: Debio 1347 (Urot…Cohort 3: Debio 1347 (All …
HyperphosphataemiaMetabolism and nutrition disorders
AlopeciaSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
DysgeusiaNervous system disorders
AnaemiaBlood and lymphatic system disorders
StomatitisGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
PyrexiaGeneral disorders
Dry eyeEye disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
ParonychiaInfections and infestations
HypomagnesaemiaMetabolism and nutrition disorders
HyperbilirubinaemiaHepatobiliary disorders
Oedema peripheralGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
InsomniaPsychiatric disorders
Alanine aminotransferase increasedInvestigations
Weight decreasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
HypercalcaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Aspartate aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
HeadacheNervous system disorders
Vision blurredEye disorders

Most-reported serious reactions: Acute kidney injury, Pyrexia, Biliary sepsis, Biliary tract infection, Dehydration, Malignant melanoma, Tumour pain, Hypotension.

Data from ClinicalTrials.gov NCT03834220 adverse events section.

Sponsor's own description

The primary objective of this study is to assess the efficacy of Debio 1347 in terms of objective response rate (ORR) in participants with solid tumors harboring fibroblast growth factor receptor (FGFR)1-3 gene fusion/rearrangement.

Publications & conference data

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

  1. Cancer-associated fibroblasts and resistance to anticancer therapies: status, mechanisms, and countermeasures.
    Feng B, Wu J, Shen B, Jiang F, et al · · 2022 · cited 150× · PMID 35488263 · DOI 10.1186/s12935-022-02599-7
  2. FGFR-TKI resistance in cancer: current status and perspectives.
    Yue S, Li Y, Chen X, Wang J, et al · · 2021 · cited 98× · PMID 33568192 · DOI 10.1186/s13045-021-01040-2
  3. 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
  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. KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities.
    Luchini C, Paolino G, Mattiolo P, Piredda ML, et al · · 2020 · cited 75× · PMID 33115526 · DOI 10.1186/s13046-020-01732-6
  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. Therapy of Primary Liver Cancer.
    Feng M, Pan Y, Kong R, Shu S. · · 2020 · cited 71× · PMID 32914142 · DOI 10.1016/j.xinn.2020.100032
  8. FGFR4: A promising therapeutic target for breast cancer and other solid tumors.
    Levine KM, Ding K, Chen L, Oesterreich S. · · 2020 · cited 68× · PMID 32492514 · DOI 10.1016/j.pharmthera.2020.107590

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Other trials of Debio 1347

Trials testing the same drug.

Other recruiting trials for Solid Tumor

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Trials by the same sponsor.

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