A Phase I/II Trial of Cabozantinib in Combination with Durvalumab (MEDI4736) with or Without Tremelimumab in Patients with Advanced Gastroesophageal Cancer and Other Gastrointestinal (GI) Malignancies (CAMILLA)
The investigators propose to evaluate the safety of drug combinations in patients with advanced gastroesophageal cancer and other gastrointestinal (GI) malignancies. Finding effective novel therapies for patients with advanced gastric cancer and other GI malignancies is an area of great unmet need. The investigators believe that modulating the tumor microenvironment with biologic agents like cabozantinib will have synergistic effect when combined with checkpoint-based immunotherapeutics like durvalumab in this patient population. This is a phase I/II, open label, multi-cohort trial looking at safety, tolerability and efficacy endpoints.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Histologically confirmed diagnosis of any of the following:
‣ Gastric or gastroesophageal junction adenocarcinoma
⁃ Esophageal adenocarcinoma
⁃ Colorectal adenocarcinoma (CRC)
⁃ Hepatocellular carcinoma (HCC)
• Patients should have advanced (stage 4) or locally unresectable (stage III) disease.
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Patients must consent to undergo a required screening/baseline biopsy procedure (and potentially another tumor biopsy at time of disease response and progression) for correlative testing.
• Patients with gastric, gastroesophageal, or esophageal adenocarcinoma must show evidence of progression or intolerance to at least one previous standard of care systemic therapy.
• Patients with CRC must show evidence of progression or intolerance to at least 2 previous standard of care systemic therapy. Ras wild type patients should fail epidermal growth factor receptor (EGFR) monoclonal antibody (panitumumab or cetuximab) to be eligible.
• Patients with HCC must must be treatment naive or show evidence of disease progression or intolerance to at least 1 previous standard of care systemic therapy.
⁃ Patients should have known tumor results for microsatellite instability (MSI) or mismatch repair (MMR) proteins. If unknown, analysis will be obtained through local pathology lab using archival tissue if available or the baseline tumor biopsy.
⁃ Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
⁃ Body weight \> 66 lbs (30 kg)
⁃ Adequate organ and marrow function.
⁃ Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
⁃ Women of child-bearing potential and men with partners of child-bearing potential must agree to use the highly effective forms of contraception prior to study entry, for the duration of study participation, and for 180 Days post completion of therapy. Men of child-bearing potential must not donate sperm while on this study and for 180 Days after their last study treatment.