Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma
- Conditions
- Gastric Adenocarcinoma
- Interventions
- Drug: Derazantinib-paclitaxel-ramucirumab combination
- Registration Number
- NCT04604132
- Lead Sponsor
- Basilea Pharmaceutica
- Brief Summary
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).
- Detailed Description
The study comprised two open-label substudies in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 gene translocations, FGFR2 gene amplifications, or FGFR1-3 mutations.
In Substudy 1, GAC patients with specified FGFR GAs, after either first- or second-line treatment, and no approved treatment alternative were treated with derazantinib 300 mg once daily or 200 mg twice daily, with the aim of evaluating the safety, tolerability, and efficacy of derazantinib monotherapy in this patient population.
In Substudy 2, GAC patients with specified FGFR GAs after standard first-line treatment, were treated with a derazantinib-paclitaxel-ramucirumab combination with the aim of evaluating the safety, tolerability, and efficacy of the combination therapy and determining the recommended phase 2 dose (RP2D).
The study originally planned to include three substudies but was prematurely terminated for administrative reasons before the third substudy (including combination therapy with derazantinib plus atezolizumab) was initiated.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 47
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 1: Cohort 1.2 Derazantinib 300 mg once daily Derazantinib Patients with FGFR1-3 mutations were treated with 300 mg Derazantinib monotherapy once daily Substudy 1: Cohort 1.3 Derazantinib 200 mg twice daily Derazantinib Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib monotherapy twice daily Substudy 2: Derazantinib 300 mg once daily+Paclitaxel+ Ramucirumab Derazantinib-paclitaxel-ramucirumab combination Patients with FGFR fusions, amplifications or mutations were treated with 300 mg Derazantinib once daily combination with Paclitaxel and Ramucirumab Substudy 2: Derazantinib 200 mg once daily +Paclitaxel+ Ramucirumab Derazantinib-paclitaxel-ramucirumab combination Patients with FGFR fusions, amplifications or mutations were treated with 200 mg Derazantinib once daily in combination with Paclitaxel and Ramucirumab Substudy 1: Cohort 1.1 Derazantinib 300 mg once daily Derazantinib Patients with FGFR2 fusions or amplifications were treated with 300 mg Derazantinib monotherapy once daily
- Primary Outcome Measures
Name Time Method Progression-free Survival at 4 Months (PFS4) in Substudy 1 in Cohort 1.3 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
Recommended Phase 2 Dose (RP2D) in Substudy 2 (Derazantinib-paclitaxel-ramucirumab in Combination) 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.
Objective Response Rate (ORR) in Substudy 1 (in Cohorts 1.1 and 1.2) 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.
- Secondary Outcome Measures
Name Time Method ORR in Substudy 1 in Cohort 1.3 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.
OS in Substudy 2 From first dose and up to 15 months OS was measured from patient enrollment to time of death
ORR in Substudy 2 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.
DCR in Substudy 2 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.
DOR in Substudy 2 (Separate and Combined Cohorts) 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).
PFS in Substudy 2 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.
Number of Patients With at Least Grade 3 Treatment-emergent Adverse Events (TEAEs) TEAEs defined as 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 Number of patients experiencing TEAE of Grade 3 and above according to Common Terminology Criteria for Adverse Events (CTCAE). CTCAE are a set of criteria for the standardized classification of TEAEs of drugs used in cancer therapy. It uses a range of grades from 1 to 5 describing increasing levels of severity of the TEAEs.
Disease Control Rate (DCR) in Substudy 1: Cohort 1.1, 1.2 and 1.3 and Combined Cohorts 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.
PFS in Substudy 1 in Cohort 1.3 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
Overall Survival (OS) in Substudy 1 in Cohort 1.3 From first dose and up to 9 months OS was measured from patient enrollment to time of death.
Trial Locations
- Locations (81)
AdventHealth Cancer Institute
🇺🇸Orlando, Florida, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Fundación Favaloro para la Docencia e Investigación Médica
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Monash Medical Centre Clayton
🇦🇺Clayton, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Australia
The Alfred Hospital
🇦🇺Prahran, Australia
UZA
🇧🇪Edegem, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
AZ Delta
🇧🇪Menen, Belgium
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