Phase Ib/II Study of Efficacy and Safety of MEK162 and Panitumumab, in Adult mCRC Patients With Mutant or Wild-type RAS Tumors

NCT01927341 | Completed Phase 1 Results

• 3 other identifiers: CMEK162X2116C42110082013-001986-18
• Study Type: interventional
• Target: 53
• Locations: 7 countries
• Sites: 8

Brief Summary

The primary purpose of the phase Ib is to estimate the MTD/RPD2 and of the phase II is to assess the anti-tumor activity of MEK162 in combination with panitumumab.

Conditions

Metastatic Colorectal Cancer

Keywords

MEK162,; panitumumab,; mutant RAS,; wild-type RAS,; metastatic colorectal cancer,; adult mCRC patient

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b

  DLT was defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment (Cycle 1) with binimetinib and panitumumab and met any of the specified criteria.

  Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1)

• Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2

  ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to \<10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  From the start of the treatment until CR or PR (approximately up to 11 months)

Secondary Outcomes (9)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE)

  Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)

• Number of Participants With Vital Sign Abnormalities

  Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)

• Number of Participants With Electrocardiogram (ECG) Abnormalities

  Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)

• Number of Participants With Clinically Significant Laboratory Abnormalities

  Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)

• Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b

  From the start of the treatment until disease progression (approximately up to 11 months)

Study Arms (5)

Phase Ib: Dose escalation

EXPERIMENTAL

Phase Ib: Dose escalation.

Drug: MEK162; Drug: Panitumumab

Phase II: Patients with mutant RAS mCRC

EXPERIMENTAL

Patients with mutant RAS mCRC who have not been pretreated with an EGFR inhibitor (EGFRi), including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.

Drug: MEK162; Drug: Panitumumab

Phase II: Patients with acquired mutant RAS mCRC

EXPERIMENTAL

Patients with acquired mutant RAS mCRC who have been pretreated with anti-EGFR monoclonal antibody therapy, but have not been pre-treated with EGFR tyrosine kinase inhibitor therapy.

Drug: MEK162; Drug: Panitumumab

Phase II: Patients with WT RAS mCRC (pretreated)

EXPERIMENTAL

Patients with WT RAS mCRC who have been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.

Drug: MEK162; Drug: Panitumumab

Phase II: Patients with WT RAS mCRC (not pretreated)

EXPERIMENTAL

Patients with WT RAS mCRC who have not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy.

Drug: MEK162; Drug: Panitumumab

Interventions

MEK162 DRUG

Tablet for oral use, 45 mg (three 15 mg tablets), BID

Phase II: Patients with WT RAS mCRC (not pretreated); Phase II: Patients with WT RAS mCRC (pretreated); Phase II: Patients with acquired mutant RAS mCRC; Phase II: Patients with mutant RAS mCRC; Phase Ib: Dose escalation

Panitumumab DRUG

Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle)

Phase II: Patients with WT RAS mCRC (not pretreated); Phase II: Patients with WT RAS mCRC (pretreated); Phase II: Patients with acquired mutant RAS mCRC; Phase II: Patients with mutant RAS mCRC; Phase Ib: Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Metastatic colorectal cancer
• Progression on or following standard therapy, or no standard therapy (phase Ib). Progression on or following at least 2-prior fluoropyrimidine-containing chemotherapy regimens (phase II)
• Written documentation of mutant or wild-type RAS
• Life expectancy ≥ 3 months
• ECOG performance status ≤ 2

You may not qualify if:

• Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors
• Previous treatment with MEK-inhibitors
• History of severe infusion reactions to monoclonal antibodies.
• Symptomatic or untreated leptomeningeal disease
• Symptomatic brain metastasis
• Current evidence of retinal disease; history of CSR, RVO or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO and history of keratitis.
• Acute or chronic pancreatitis
• Clinically significant cardiac disease
• Not adequate hematologic, renal and hepatic function

Sponsors & Collaborators

• Pfizer: lead

Study Sites (8)

University of California at Los Angeles Dept of Onc

Los Angeles, California, 90095, United States

Location

Memorial Sloan Kettering Cancer Center Oncology Dept

New York, New York, 90033, United States

Location

Pfizer Investigative Site

Leuven, 3000, Belgium

Location

Pfizer Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Pfizer Investigative Site

Toulouse, 31059, France

Location

Pfizer Investigative Site

Milan, MI, 20162, Italy

Location

Pfizer Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Pfizer Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Related Publications (1)

• Van Cutsem E, Yaeger R, Delord JP, Tabernero J, Siu LL, Ducreux M, Siena S, Elez E, Kasper S, Zander T, Steeghs N, Murphy D, Edwards M, Wainberg ZA. Phase Ib/II Study of the Efficacy and Safety of Binimetinib (MEK162) Plus Panitumumab for Mutant or Wild-Type RAS Metastatic Colorectal Cancer. Oncologist. 2023 Dec 11;28(12):e1209-e1218. doi: 10.1093/oncolo/oyad210.

  PMID: 37597246 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

binimetinib; Panitumumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study used binimetinib 45 mg BID and panitumumab 6 mg/kg intravenous infusion once every second week, there was no planned dose escalation.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2013
• First Posted: August 22, 2013
• Study Start: November 19, 2013
• Primary Completion: January 25, 2016
• Study Completion: January 25, 2016
• Last Updated: February 18, 2021
• Results First Posted: February 18, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); BE (1); ES (1); US (2); NL (1); FR (1); IT (1)