A Study Of MEK162 And AMG 479 In Patients With Selected Solid Tumors

Study Overview

A Study of MEK162 and AMG 479 in Patients With Selected 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.

N/A

Metastatic Pancreatic Adenocarcinoma
BRAF Mutated Melanoma

DRUG: MEK162
DRUG: AMG 479

CMEK162X2111
C4211010 (OTHER Identifier) (OTHER: Alias Study Number)
2012-000305-76 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2012-03-22	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-12-09
First Submitted that Met QC Criteria 2012-03-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-12-10
First Posted (ACTUAL) 2012-03-26	Results First Posted N/A	Last Verified 2020-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
N/A

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Dose escalation Dose finding group chosen in order to establish a safe and tolerated dose of binimetinib in combination with ganitumab in patients with selected advanced solid tumors.	DRUG: MEK162 Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure. DRUG: AMG 479 Supplied as sterile liquid for intravenous infusion in vials in boxes. Until April 2013 a frozen formulation with a concentration of 30 mg/ml was used; from May 2013 onwards a refrigerated formulation with a concentration of 70 mg/ml was used.
EXPERIMENTAL: KRAS mutated colorectal adenocarcinoma Patients with KRAS mutant colorectal cancer. The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q	DRUG: MEK162 Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure. DRUG: AMG 479 Supplied as sterile liquid for intravenous infusion in vials in boxes. Until April 2013 a frozen formulation with a concentration of 30 mg/ml was used; from May 2013 onwards a refrigerated formulation with a concentration of 70 mg/ml was used.
EXPERIMENTAL: Metastatic pancreatic adenocarcinoma Patients with metastatic pancreatic cancer. The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q2	DRUG: MEK162 Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure. DRUG: AMG 479 Supplied as sterile liquid for intravenous infusion in vials in boxes. Until April 2013 a frozen formulation with a concentration of 30 mg/ml was used; from May 2013 onwards a refrigerated formulation with a concentration of 70 mg/ml was used.
EXPERIMENTAL: BRAF mutated melanoma Patients with mutant BRAF V600 melanoma. The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q2w w	DRUG: MEK162 Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure. DRUG: AMG 479 Supplied as sterile liquid for intravenous infusion in vials in boxes. Until April 2013 a frozen formulation with a concentration of 30 mg/ml was used; from May 2013 onwards a refrigerated formulation with a concentration of 70 mg/ml was used.

Primary Outcome Measures	Measure Description	Time Frame
Phase Ib: Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) by measuring incidence of dose limiting toxicities	To estimate the MTDs and/or RP2Ds of MEK162 in combination with AMG479 by measuring incidence of dose limiting toxicities in Cycle 1 (Cycle 1 = 28 days)	Approximately 6 months
Phase II: Antitumor activity of MEK162 in combination with AMG 479 by evaluating Objective Response Rate (ORR) in colorectal carcinoma and melanoma and by evaluating Disease Control Rate (DCR) at week 10 in pancreatic carcinoma	To estimate the antitumor activity of MEK162 in combination with AMG479 by evaluating Objective Response Rate (ORR) according to RECIST 1.1 in colorectal carcinoma and melanoma and by evaluating the Disease Control Rate (DCR) per RECIST 1.1 at week 10 in pancreatic carcinoma	Approximately 24 months

Secondary Outcome Measures	Measure Description	Time Frame
Both Phases: Safety and tolerability of MEK162 & AMG 479 (ganitumab) in combination by evaluating the adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs; dose interruptions, reductions and dose intensity	To characterize the safety and tolerability of MEK162 and AMG 479 (ganitumab) in combination by evaluating the incidence and severity of adverse events, serious adverse events (as per CTCAE grading), changes in hematology and chemistry values, vital signs, ECGs; dose interruptions, reductions and dose intensity	Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
Both Phases: Determination of single and multiple dose pharmacokinetics (PK) profile of MEK162 in combination with AMG 479 (ganitumab) by measuring time vs. plasma concentrations and basic PK parameters of MEK162	To determine single and multiple dose PK profile of MEK162 in combination with AMG 479 (ganitumab) by measuring time vs. plasma concentration as well as basic PK parameters of MEK162 at different timepoints prior and post study drug combination dosing.	Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
Phase Ib: Preliminary anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating the Overall Response Rate (ORR), Duration of Response (DOR) and Progression Free Survival (PFS)	To assess preliminary anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating Overall Response Rate (ORR), Duration of Response (DOR), Progression Free Survival (PFS) as assessed by the investigator according to RECIST 1.1	Approximately 6 months
Phase II: Further anti-tumor activity of MEK162 & AMG 479 (ganitumab) in combination by evaluating the DOR, PFS and OS by evaluating Disease Control Rate for colorectal carcinoma and melanoma; Overall Response Rate for pancreatic carcinoma patients	To further assess the anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating the Duration of Response (DOR) and Progression Free Survival (PFS) per RECIST 1.1 and Overall Survival in all phase II patients and by evaluating the Disease Control Rate (DCR) per RECIST 1.1 for colorectal carcinoma and melanoma and Overall Response Rate (ORR) per RECIST 1.1 for pancreatic carcinoma patients	Approximately 24 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Pfizer CT.gov Call Center, Pfizer

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record