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A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors

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ClinicalTrials.gov Identifier: NCT01562899
Recruitment Status : Terminated (Study was withdrawn due to scientific and business considerations.)
First Posted : March 26, 2012
Last Update Posted : December 10, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma BRAF Mutated Melanoma Drug: MEK162 Drug: AMG 479 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 27, 2012
Actual Primary Completion Date : April 1, 2015
Actual Study Completion Date : April 1, 2015

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Binimetinib

Arms and Interventions
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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.
Other Name: Binimetinib

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.
Other Name: Ganitumab
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 q2w which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.

 Drug: MEK162
Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.
Other Name: Binimetinib

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.
Other Name: Ganitumab
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 q2w which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.

 Drug: MEK162
Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.
Other Name: Binimetinib

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.
Other Name: Ganitumab
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 which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.

 Drug: MEK162
Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.
Other Name: Binimetinib

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.
Other Name: Ganitumab


Outcome Measures
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Primary Outcome Measures :
  1. Phase Ib: Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) by measuring incidence of dose limiting toxicities [ Time Frame: Approximately 6 months ]
    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)

  2. 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 [ Time Frame: Approximately 24 months ]
    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


Secondary Outcome Measures :
  1. 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 [ Time Frame: Phase Ib: Approximately 6 months; Phase II: Approximately 24 months ]
    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

  2. 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 [ Time Frame: Phase Ib: Approximately 6 months; Phase II: Approximately 24 months ]
    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.

  3. 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) [ Time Frame: Approximately 6 months ]
    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

  4. 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 [ Time Frame: Approximately 24 months ]
    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


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01562899


Locations
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United States, Massachusetts
Massachusetts General Hospital Mass General 2
Boston, Massachusetts, United States, 02114
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman
Salt Lake City, Utah, United States, 84103
Australia, Victoria
Pfizer Investigative Site
Parkville, Victoria, Australia, 3050
Belgium
Pfizer Investigative Site
Leuven, Belgium, 3000
Canada, Ontario
Pfizer Investigative Site
Toronto, Ontario, Canada, M5G 2M9
France
Pfizer Investigative Site
Toulouse Cedex 9, France, 31059
Italy
Pfizer Investigative Site
Napoli, Italy, 80131
Spain
Pfizer Investigative Site
Barcelona, Catalunya, Spain, 08035
United Kingdom
Pfizer Investigative Site
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01562899    
Other Study ID Numbers: CMEK162X2111
C4211010 ( Other Identifier: Alias Study Number )
2012-000305-76 ( EudraCT Number )
First Posted: March 26, 2012    Key Record Dates
Last Update Posted: December 10, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Keywords provided by Pfizer:
MEK162
AMG 479
Ganitumab
colorectal adenocarcinoma
 pancreatic adenocarcinoma
melanoma
KRAS
BRAF
Additional relevant MeSH terms:
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Melanoma
Adenocarcinoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
 Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Carcinoma
Neoplasms, Glandular and Epithelial