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).
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
Interventions
Drug | Synonyms | Arms |
---|
Derazantinib | | Derazantinib |
Derazantinib-paclitaxel-ramucirumab | | Derazantinib-paclitaxel-ramucirumab |
Derazantinib-atezolizumab | | Derazantinib-atezolizumab |
Paclitaxel-ramucirumab | | Standard 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
Name | Type | Description | Interventions |
---|
Derazantinib | Experimental | In 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-paclitaxel-ramucirumab | Experimental | In 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-atezolizumab | Experimental | In 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 care | Active Comparator | In 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. | |
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 (FGFR2 fusions / rearrangements /
amplifications; FGFR1, FGFR2, or FGFR3 mutations / short variants)
- 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
August 13, 2021