Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma (FIDES-03)
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| ClinicalTrials.gov Identifier: NCT04604132 |
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Recruitment Status :
Terminated
(Terminated prematurely for administrative reasons not related to patient safety.)
First Posted : October 27, 2020
Last Update Posted : February 16, 2023
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Sponsor:
Basilea Pharmaceutica
Information provided by (Responsible Party):
Basilea Pharmaceutica
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Brief Summary:
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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Gastric Adenocarcinoma | Drug: Derazantinib Drug: Derazantinib-paclitaxel-ramucirumab Drug: Derazantinib-atezolizumab Drug: Paclitaxel-ramucirumab | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 47 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | October 6, 2020 |
| Actual Primary Completion Date : | December 29, 2022 |
| Actual Study Completion Date : | December 29, 2022 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Derazantinib
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.
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Drug: Derazantinib
Derazantinib will be administered orally at a dose of 300 mg once a day and at a dose of 200 mg twice daily as monotherapy in the Substudy 1. |
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Experimental: Derazantinib-paclitaxel-ramucirumab
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.
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Drug: Derazantinib-paclitaxel-ramucirumab
Derazantinib will be administered at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 in combination with paclitaxel and ramucirumab. Paclitaxel will be administered intravenously at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 on days 1, 8, and 15 of a 28-day cycle in combination with derazantinib and ramucirumab. Ramucirumab will be administered intravenously at the RP2D for derazantinib-paclitaxel-ramucirumab determined in Substudy 2 every 2 weeks in combination with derazantinib and paclitaxel. |
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Experimental: Derazantinib-atezolizumab
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.
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Drug: Derazantinib-atezolizumab
Derazantinib will be administered orally at a dose of 300 mg once a day in combination with atezolizumab. Atezolizumab will be administered intravenously at a dose of 1200 mg every 3 weeks in combination with derazantinib. |
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Active Comparator: Standard of care
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.
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Drug: Paclitaxel-ramucirumab
Paclitaxel will be administered intravenously at a dose of 80 mg/m² on days 1, 8, and 15 of a 28-day cycle in combination with ramucirumab. Ramucirumab will be administered intravenously at a dose of 8 mg/kg every 2 weeks in combination with paclitaxel. |
Primary Outcome Measures :
- Objective response rate (ORR) per RECIST 1.1 in Substudy 1 (in two subgroups Cohort 1.1 and 1.2) and Substudy 3) [ Time Frame: Approximately 30 months ]ORR will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) by blinded independent central review (BICR).
- 4-month progression-free survival rate (PFS4, in a subgroup (Cohort 1.3) within Substudy 1) [ Time Frame: Approximately 18 months ]PFS4 will be measured by the proportion of patients alive and free of disease progression by blinded independent central review (BICR) per RECIST. 1.1
- Recommended phase 2 dose (RP2D) of derazantinib-paclitaxel-ramucirumab in combination (Substudy 2) [ Time Frame: Approximately 18 months ]RP2D will be 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 combination.
Secondary Outcome Measures :
- ORR per RECIST 1.1 in subgroup Cohort 1.3 within Substudy 1and in Substudy 3 [ Time Frame: Approximately 24 months ]ORR will be measured by the proportion of patients with confirmed complete response (CR) or partial response (PR) by blinded independent central review (BICR).
- Disease Control Rate (DCR) [ Time Frame: Approximately 24 months ]Measured by the proportion of patients with confirmed CR, PR or stable disease (SD) by BICR
- Duration of Response (DOR) [ Time Frame: Approximately 24 months ]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)
- Progression-free Survival (PFS) [ Time Frame: Approximately 24 months ]PFS will be measured from patient enrollment to progressive disease (PD) date by BICR
- Overall Survival (OS) [ Time Frame: Approximately 24 months ]OS will be measured from patient enrollment to time of death
- Pharmacokinetic (PK) profile: Peak Plasma Concentration (Cmax) of derazantinib 200 mg twice daily monotherapy [ Time Frame: Approximately 24 months ]Derazantinib plasma concentrations including Cmax will be assessed by measurements in plasma samples
- Pharmacokinetic (PK) profile: Area under the plasma concentration versus time curve (AUC) of derazantinib 200 mg twice daily monotherapy [ Time Frame: Approximately 24 months ]AUC will be assessed by measurements of derazantinib in plasma samples
- Pharmacokinetic (PK) profile: The time to reach Cmax (Tmax) of derazantinib 200 mg twice daily monotherapy [ Time Frame: Approximately 24 months ]Tmax will be assessed by measurements of derazantinib in plasma samples
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
- 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:
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Prior anticancer or investigational drug treatment within an interval shorter than the following, as applicable:
- One chemotherapy or biological (e.g., antibody) cycle interval
- Five half-lives of any small molecule investigational or licensed medicinal product
- Two weeks, for any investigational medicinal product with an unknown half-life
- Four weeks of curative radiotherapy
- Seven days of palliative 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
- Known CNS metastases
- Concurrent uncontrolled or active infection with human immunodeficiency virus (HIV; known HIV 1/2 antibodies positive); active or chronic hepatitis B without current antiviral therapy and an HBV DNA ≥ 100 IU/mL virus (HBV); active 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)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04604132
Locations
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Sponsors and Collaborators
Basilea Pharmaceutica
Investigators
| Study Director: | Manuel Häckl, MD | Basilea Pharmaceutica International Ltd |
| Responsible Party: | Basilea Pharmaceutica |
| ClinicalTrials.gov Identifier: | NCT04604132 |
| Other Study ID Numbers: |
DZB-CS-202 |
| First Posted: | October 27, 2020 Key Record Dates |
| Last Update Posted: | February 16, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Basilea Pharmaceutica:
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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 |
Additional relevant MeSH terms:
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Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Paclitaxel Albumin-Bound Paclitaxel Atezolizumab Ramucirumab |
Antibodies, Monoclonal Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs |