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NCT04604132: FIDES-03

Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma

Terminated Phase 1, PHASE2 Results posted Last updated 4 April 2024
What this trial tests

Phase 1, PHASE2 trial testing Derazantinib in Gastric Adenocarcinoma in 47 participants. Terminated before completion.

Timeline
6 October 2020
Primary endpoint
21 November 2022
21 November 2022

Quick facts

Lead sponsorBasilea Pharmaceutica
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment47
Start date6 October 2020
Primary completion21 November 2022
Estimated completion21 November 2022
Sites81 locations across France, Italy, Russia, Belgium, Chile, United Kingdom, Germany, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Basilea Pharmaceutica — full company profile →

Who can join

18 and older, any sex, with Gastric Adenocarcinoma. 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) in Substudy 1 (in Cohorts 1.1 and 1.2) Primary · From first dose and up to 18 months

ORR was defined by the percentage of patients with confirmed complete response (CR, which means disappearance of all target lesions) or partial response (PR, which means \>=30% decrease in the sum of the longest diameter of target lesions) by blinded independent central review (BICR) using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST 1.1). Overall Response (OR) = CR + PR. The patients in Cohort 1.1 had FGFR2 fusions or amplification gastric adenocarcinoma (GAC) and FGFR1-3 mutations GAC in Cohort 1.2.

GroupValue95% CI
Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily0.00.0 – 20.6
Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily0.00.0 – 31.2
Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3 Primary · From first dose and up to 4 months

PFS4 was defined by the percentage of patients alive and free of disease progression (defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions) by BICR per RECIST. 1.1. Patients in this Cohort had FGFR fusions, amplifications or mutations GAC

GroupValue95% CI
Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily7.70.4 – 31.6
Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination) Primary · From first dose and up to 18 months

RP2D was determined from safety and tolerability according to the aggregate of dose-limiting toxicity criteria and adverse event (AE) data, and considering further pharmacokinetic and efficacy data of the derazantinib-paclitaxel-ramucirumab combination in patients with FGFR fusions, amplifications or mutations GAC.

GroupValue95% CI
Substudy 2 Combined: Derazantinib +Paclitaxel+ Ramucirumab200
ORR in Substudy 1 in Cohort 1.3 Secondary · From first dose and up to 9 months

ORR was defined by the percentage of patients with CR or PR by BICR according to RECIST Version 1.1.

GroupValue95% CI
Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily0.00.0 – 20.6
Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts Secondary · From first dose and up to 18 months

Defined as the percentage of patients with confirmed CR, PR or stable disease (SD) by BICR per RECIST version 1.1.

GroupValue95% CI
Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily30.811.3 – 57.3
Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily25.04.6 – 60.0
Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily15.42.8 – 41.0
Substudy 1 Combined: Derazantinib 300 mg Once Daily or 200 mg Twice Daily23.512.3 – 38.5
PFS in Substudy 1 in Cohort 1.3 Secondary · From first dose and up to 9 months

PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1

GroupValue95% CI
Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily1.71.0 – 1.9
Overall Survival (OS) in Substudy 1 in Cohort 1.3 Secondary · From first dose and up to 9 months

OS was measured from patient enrollment to time of death.

GroupValue95% CI
Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily3.32.2 – 3.7
OS in Substudy 2 Secondary · From first dose and up to 15 months

OS was measured from patient enrollment to time of death

GroupValue95% CI
Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab5.52.7 – NA
Substudy 2: Derazantinib 300 mg Once Daily + Paclitaxel + RamucirumabNANA – NA
ORR in Substudy 2 Secondary · From first dose and up to 15 months

ORR was defined by the percentage of patients with CR or PR by BICR per RECIST version 1.1.

GroupValue95% CI
Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab40.07.6 – 81.1
Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ Ramucirumab57.122.5 – 87.1
DCR in Substudy 2 Secondary · From first dose and up to 15 months

Defined as the percentage of patients with confirmed CR, PR or SD by BICR per RECIST version 1.1.

GroupValue95% CI
Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab80.034.3 – 99.0
Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel + Ramucirumab71.434.1 – 94.7
Substudy 2 Combined: Derazantinib +Paclitaxel+ Ramucirumab75.047.3 – 92.8
DOR in Substudy 2 (Separate and Combined Cohorts) Secondary · From first dose and up to 15 months

DOR was calculated from the first date of documented tumor response to disease progression by BICR per RECIST version 1.1 (or death if no documentation of PD is obtained).

GroupValue95% CI
Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab9.2NA – NA
Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ RamucirumabNA3.3 – NA
Substudy 2 Combined: Derazantinib +Paclitaxel+ Ramucirumab9.23.3 – NA
PFS in Substudy 2 Secondary · From first dose and up to 15 months

PFS was calculated from patient enrollment to progressive disease (PD) date by BICR per RECIST version 1.1.

GroupValue95% CI
Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab11.11.6 – NA
Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ RamucirumabNA1.7 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs which were assessed per patient from the patient's first dose and until 90 days after the last dose, which corresponded up to 19 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Substudy 1: Cohort 1.1 Derazantinib 300 mg Once Daily
Serious: 7/13 (54%)
Deaths: 10/13
Substudy 1: Cohort 1.2 Derazantinib 300 mg Once Daily
Serious: 4/8 (50%)
Deaths: 6/8
Substudy 1: Cohort 1.3 Derazantinib 200 mg Twice Daily
Serious: 10/13 (77%)
Deaths: 10/13
Substudy 2: Derazantinib 200 mg Once Daily +Paclitaxel+ Ramucirumab
Serious: 4/6 (67%)
Deaths: 4/6
Substudy 2: Derazantinib 300 mg Once Daily +Paclitaxel+ Ramucirumab
Serious: 3/7 (43%)
Deaths: 0/7

Serious adverse events (23 terms)

ReactionSystemSubstudy 1: Cohort 1.1 Der…Substudy 1: Cohort 1.2 Der…Substudy 1: Cohort 1.3 Der…Substudy 2: Derazantinib 2…Substudy 2: Derazantinib 3…
Disease progressionGeneral disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Acute coronary syndromeCardiac disorders
AnaemiaBlood and lymphatic system disorders
EncephalopathyNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
Anal haemorrhageGastrointestinal disorders
StomatitisGastrointestinal disorders
Diabetic ketoacidosisMetabolism and nutrition disorders
COVID-19 pneumoniaInfections and infestations
PneumoniaInfections and infestations
SepsisInfections and infestations
Metastases to meningesNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AstheniaGeneral disorders
General physical health deteriorationGeneral disorders
PyrexiaGeneral disorders
Hepatic cytolysisHepatobiliary disorders
Hepatic failureHepatobiliary disorders
HyperbilirubinaemiaHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
Other adverse events (126 terms — click to expand)

ReactionSystemSubstudy 1: Cohort 1.1 Der…Substudy 1: Cohort 1.2 Der…Substudy 1: Cohort 1.3 Der…Substudy 2: Derazantinib 2…Substudy 2: Derazantinib 3…
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
NauseaGastrointestinal disorders
Blood alkaline phosphatase increasedInvestigations
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
AstheniaGeneral disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
Neck painMusculoskeletal and connective tissue disorders
HyperphosphataemiaMetabolism and nutrition disorders
Amylase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Lipase increasedInvestigations
Neutrophil count decreasedInvestigations
LeukopeniaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
DizzinessNervous system disorders
Peripheral sensory neuropathyNervous system disorders
Dry eyeEye disorders
Abdominal painGastrointestinal disorders
Dry mouthGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
StomatitisGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
Blood albumin decreasedInvestigations
Blood bilirubin increasedInvestigations
Blood creatinine increasedInvestigations
Blood glucose increasedInvestigations
Blood phosphorus increasedInvestigations
Blood potassium increasedInvestigations
C-reactive protein increasedInvestigations
Electrocardiogram QT prolongedInvestigations

Most-reported serious reactions: Disease progression, Pulmonary embolism, Acute coronary syndrome, Anaemia, Encephalopathy, Dyspnoea, Pneumonitis, Abdominal pain.

Data from ClinicalTrials.gov NCT04604132 adverse events section.

Sponsor's own description

The purpose of this study was to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel and ramucirumab in patients with gastric adenocarcinoma (GAC) i.e. with human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring fibroblast growth factor receptor 2 (FGFR2) genetic aberrations (GA).

Publications & conference data

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

  1. 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
  2. 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
  3. Targeting FGFR2 Positive Gastroesophageal Cancer: Current and Clinical Developments.
    Gordon A, Johnston E, Lau DK, Starling N. · · 2022 · cited 25× · PMID 36238135 · DOI 10.2147/ott.s282718
  4. Overcoming physical stromal barriers to cancer immunotherapy.
    Chung SW, Xie Y, Suk JS. · · 2021 · cited 20× · PMID 34351575 · DOI 10.1007/s13346-021-01036-y
  5. FGFR Pathway Inhibition in Gastric Cancer: The Golden Era of an Old Target?
    Lengyel CG, Hussain S, Seeber A, Jamil Nidhamalddin S, et al · · 2022 · cited 18× · PMID 35054474 · DOI 10.3390/life12010081
  6. Diffuse Gastric Cancer: A Comprehensive Review of Molecular Features and Emerging Therapeutics.
    Wu LW, Jang SJ, Shapiro C, Fazlollahi L, et al · · 2024 · cited 13× · PMID 39271577 · DOI 10.1007/s11523-024-01097-2
  7. Clinical Developments and Challenges in Treating FGFR2-Driven Gastric Cancer.
    Lau DK, Collin JP, Mariadason JM. · · 2024 · cited 11× · PMID 38791079 · DOI 10.3390/biomedicines12051117
  8. Probing the Effects of the FGFR-Inhibitor Derazantinib on Vascular Development in Zebrafish Embryos.
    Kotini MP, Bachmann F, Spickermann J, McSheehy PM, et al · · 2020 · cited 4× · PMID 33396726 · DOI 10.3390/ph14010025

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