A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors
Phase: Phase 2
Diagnosis: Gastrointestinal Malignancies
NCT ID: NCT01562899
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 12-260
This is a multi-center, open-label, phase Ib/II study. First, the aim of the phase Ib part is to estimate the MTD(s) and/or to identify the recommended phase II dose(s) (RP2D) for the combination of MEK162 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study will be guided by a Bayesian Logistic Regression Model (BLRM). At least 18 patients are expected to be enrolled in the dose escalation part. Following MTD/ RP2D declaration, patients will be enrolled in three phase II arms to assess efficacy of the combination as well as to better understand the safety, tolerability, PK, antibody concentrations and PD of the combination at MTD/RP2D. Phase II arm 1 will consist of approximately 25 patients with KRAS-mutant colorectal adenocarcinoma. Phase II arm 2 will consist of approximately 20 patients with metastatic pancreatic adenocarcinoma. Phase II arm 3 will consist of approximately 28 patients with mutant BRAFV600 melanoma. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. All patients will be followed up - at minimum patients must complete the safety follow-up assessments 30 days after the last dose of the study treatment. Patients who have not progressed at the time of discontinuation of study treatment should be radiologically followed for the disease status and phase II patients will be followed for survival.
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital
Charles Fuchs, MD, MPH,
Dana-Farber Cancer Institute
Dana-Farber Cancer Institute:
Gastrointestinal Research Line, 617-632-5960
- Patients aged ≥ 18 years
- Patients with advanced solid tumors (CRC, melanoma) with documented somatic KRAS or
BRAFV600 mutations in tumor tissue. Patients with metastatic pancreatic
adenocarcinoma may be enrolled irrespectively of KRAS or BRAFV600 mutational status.
- Patients must have relapsed or progressed following standard therapy or patients for
whom no standard anticancer therapy exists.
- Measurable disease as determined by RECIST v1.1. World Health Organization (WHO)
Performance Status (PS) ≤ 2.
- Adequate organ function
- Negative serum pregnancy test
- Prior therapy with MEK- or IGF-1R- inhibitor
- History or current evidence of central serous retinopathy (CSR), retinal vein
occlusion (RVO) or retinal degenerative disease
- Patients with known history of severe infusion reactions to monoclonal antibodies
- Patients with primary CNS tumor or CNS tumor involvement
- History of thromboembolic event requiring full-dose anticoagulation therapy
- Clinically significant cardiac disease
- History of another malignancy within 2 years
- Pregnant or nursing (lactating) women
Other protocol-defined inclusion/exclusion criteria may apply