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

• Status: Recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Basilea Pharmaceutica
• Treatments: Albumin-Bound Paclitaxel; Antibodies, Monoclonal; Atezolizumab; Paclitaxel; Ramucirumab

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)