Clinical Trials /

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

NCT04604132

Description:

The purpose of this study is to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 genetic aberrations (GA).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma
  • Official Title: A Phase 1b/2 Study of Derazantinib as Monotherapy and Combination Therapy With Paclitaxel, Ramucirumab or Atezolizumab in Patients With HER2-negative Gastric Adenocarcinoma Expressing FGFR2 Genetic Aberrations

Clinical Trial IDs

  • ORG STUDY ID: DZB-CS-202
  • NCT ID: NCT04604132

Conditions

  • Gastric Adenocarcinoma

Interventions

DrugSynonymsArms
DerazantinibDerazantinib
Derazantinib-paclitaxel-ramucirumabDerazantinib-paclitaxel-ramucirumab
Derazantinib-atezolizumabDerazantinib-atezolizumab
Paclitaxel-ramucirumabStandard of care

Purpose

The purpose of this study is to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 genetic aberrations (GA).

Detailed Description

      The study comprises three 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. Patients will be treated with single-agent derazantinib
      or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab. The study
      enrolls patients with either metastatic or recurrent locally advanced HER2-negative
      adenocarcinoma of the stomach or gastro-esophageal junction inoperable at the time of
      screening, and radiologically confirmed disease progression after one or at least one
      standard treatment regimen.
    

Trial Arms

NameTypeDescriptionInterventions
DerazantinibExperimentalIn Substudies 1 and 3.1, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib.
  • Derazantinib
Derazantinib-paclitaxel-ramucirumabExperimentalIn Substudies 2 and 3.2, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib-paclitaxel-ramucirumab in combination.
  • Derazantinib-paclitaxel-ramucirumab
Derazantinib-atezolizumabExperimentalIn Substudy 3.3, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive derazantinib-atezolizumab in combination.
  • Derazantinib-atezolizumab
Standard of careActive ComparatorIn Substudy 3.4, patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR genetic aberrations will receive the Standard of Care drugs paclitaxel-ramucirumab in combination.
  • Paclitaxel-ramucirumab

Eligibility Criteria

        Key Inclusion Criteria:

          -  Histologically-confirmed adenocarcinoma of the gastro-esophageal junction or stomach

          -  Male or female aged ≥ 18 years

          -  Negative HER2 status obtained from the most recent available tissue sample

          -  Inoperable recurrent, locally advanced adenocarcinoma or progressing stage IV
             adenocarcinoma of the gastro-esophageal junction or stomach, and disease progression
             after either standard first- or second-line treatment (Substudy 1), or after standard
             first-line treatment (Substudies 2 and 3)

          -  Positive test for eligible FGFR aberrations

          -  For Substudies 1 and 3, measurable disease as defined by the Investigator using RECIST
             1.1 criteria

          -  ECOG PS of 0 or 1

          -  Men and women of childbearing potential must agree to avoid impregnating a partner or
             becoming pregnant, respectively, during the study, and for at least 150 days after the
             last dose of either investigational drug

        Key Exclusion Criteria:

          -  Prior anticancer or investigational drug treatment within an interval shorter than the
             following, as applicable:

               1. One chemotherapy or biological (e.g., antibody) cycle interval

               2. Five half-lives of any small molecule investigational or licensed medicinal
                  product

               3. Two weeks, for any investigational medicinal product with an unknown half-life

               4. Four weeks of curative radiotherapy

               5. Seven days of palliative radiotherapy

               6. 28 days of radiotherapy

          -  Prior treatment with FGFR Inhibitors (all substudies), and prior treatment with
             taxanes within 6 months prior to randomization and/or anti-VEGF(R) therapeutic
             antibody or pathway-targeting agents (Substudies 2 and 3), and prior treatment with
             anti-programmed cell death receptor-1 (PD-1) or anti-programmed death ligand-1 (PD-L1)
             therapeutic antibody or pathway-targeting agents (Substudy 3)

          -  Concurrent evidence of clinically significant corneal or retinal disorder

          -  History of clinically significant cardiac disorders and/or a QT interval corrected by
             Fridericia's formula (QTcF) > 450 ms for males or > 460 ms for females

          -  For Substudies 1 and 3, known CNS metastases

          -  Concurrent uncontrolled or active infection with human immunodeficiency virus (HIV;
             known HIV 1/2 antibodies positive); active hepatitis B virus (HBV) and hepatitis C
             virus (HCV) co-infection; active tuberculosis (for Substudies 2 and 3)

          -  Child-Pugh B or C liver cirrhosis, or a history of hepatic encephalopathy, hepatorenal
             syndrome, or clinically-meaningful ascites related to cirrhosis (for Substudies 2 and
             3)

          -  Administration of a live, attenuated vaccine within 30 days prior to randomization
             (for Substudy 3)

          -  Treatment with systemic corticosteroids (except for steroidal replacement therapy) or
             other systemic immunosuppressive medications within 2 weeks prior to first dose of
             study drug or anticipated requirement for systemic immunosuppressive medications
             during the study (for Substudy 3)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR) per RECIST 1.1 (Substudies 1 and 3)
Time Frame:Approximately 30 months
Safety Issue:
Description:ORR of will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) by blinded independent central review (BICR).

Secondary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:Approximately 2 years
Safety Issue:
Description:PFS will be measured from patient enrollment to progressive disease (PD) date by BICR
Measure:Disease Control Rate (DCR)
Time Frame:Approximately 2 years
Safety Issue:
Description:Measured by the proportion of patients with confirmed CR, PR or stable disease (SD) by BICR
Measure:Duration of Response (DOR)
Time Frame:Approximately 2 years
Safety Issue:
Description:DOR will be calculated from the first date of documented tumor response to disease progression by BICR (or death if no documentation of PD is obtained)
Measure:Overall Survival (OS)
Time Frame:Approximately 2 years
Safety Issue:
Description:OS will be measured from patient enrollment to time of death

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Basilea Pharmaceutica

Trial Keywords

  • gastric cancer
  • gastro-esophageal adenocarcinoma
  • adenocarcinoma of the stomach or gastro-esophageal junction
  • fibroblast growth factor receptor
  • FGFR genetic aberration
  • targeted therapy
  • derazantinib
  • atezolizumab
  • Tecentriq
  • paclitaxel
  • ramucirumab
  • Cyramza
  • solid tumor

Last Updated

June 18, 2021