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

Pfizer

Status and phase: Completed; Phase 2; Phase 1

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Panitumumab; Drug: MEK162

Study type: Interventional

Funder types: Industry

Identifiers

NCT01927341

C4211008 (Other Identifier)

CMEK162X2116

2013-001986-18 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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53 participants in 5 patient groups

Phase Ib: Dose escalation

Experimental group

Description:

Phase Ib: Dose escalation.

Treatment:

Drug: Panitumumab

Drug: MEK162

Phase II: Patients with mutant RAS mCRC

Experimental group

Description:

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.

Treatment:

Drug: Panitumumab

Drug: MEK162

Phase II: Patients with acquired mutant RAS mCRC

Experimental group

Description:

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.

Treatment:

Drug: Panitumumab

Drug: MEK162

Phase II: Patients with WT RAS mCRC (pretreated)

Experimental group

Description:

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.

Treatment:

Drug: Panitumumab

Drug: MEK162

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

Experimental group

Description:

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.

Treatment:

Drug: Panitumumab

Drug: MEK162