A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors
| Status: | Terminated |
|---|---|
| Conditions: | Colorectal Cancer, Skin Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/16/2017 |
| Start Date: | August 2012 |
| End Date: | April 2015 |
A Phase Ib/II Open-label, Multi-center Study of the Combination of MEK162 Plus AMG 479 (Ganitumab) in Adult Patients With Selected Advanced Solid Tumors
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.
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.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
We found this trial at
3
sites
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