MEK162 for Patients With RAS/RAF/MEK Activated Tumors (SIGNATURE)

Pfizer

Status and phase: Completed; Phase 2

Conditions: Solid Tumor and Hematologic Malignancies

Treatments: Drug: MEK162

Study type: Interventional

Funder types: Industry

Identifiers

NCT01885195

C4211007 (Other Identifier)

CMEK162AUS11

Details and patient eligibility

About

The purpose of this signal seeking study is to determine whether treatment with MEK162 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study

Full description

This is a phase II, open label study to determine the efficacy and safety of treatment with MEK162 in patients with a diagnosis of select solid tumors or hematological malignancies that have been pre-identified (prior to study consent) to have activations of the RAS/RAF/MEK pathway and whose disease has progressed on or after standard treatment.

Genomic profiling is becoming more accessible to patients and their physicians. This is a signal-seeking study to match patients with mutations in RAF, RAS, NF1 or MEK to the ATP-noncompetitive MEK 1/2 inhibitor, MEK162. Pre-identification of these mutations or activations in the pathway will be performed locally at a CLIA certified laboratory prior to screening for participation on the trial.

Once the patient has been identified, treating physicians who are qualified investigators may contact Novartis to consider enrollment in this study. For the purpose of this study, genomic profiling is not considered part of screening. Informed consent must be signed before any screening activities take place. Once eligibility (screening criteria met) has been confirmed by Novartis, the patient will initiate therapy with single agent MEK162. The patient may not receive any additional anti-cancer therapy during treatment with MEK162.

Patients will continue to receive study treatment until disease progression (assessed by RECIST 1.1 or appropriate hematologic response criteria), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment. All patients who discontinue from study treatment due to disease progression must have their progression clearly documented.

Disease assessment (per RECIST 1.1 or appropriate hematological response criteria) will be performed every 8 weeks (±4 days) after first dose of study drug (Day 1 of every odd cycle), until disease progression or end of treatment, whichever occurs first. The frequency of disease assessment may be reduced to every 12 weeks for patients who have at least 4 post-baseline disease assessments and are clinically stable (except AML and MM patients). Scans will be assessed locally by the investigator. After discontinuation of treatment, patients, regardless of reason for treatment discontinuation, will be followed for safety for 30 days after the last dose.

All patients will be followed for survival status every 3 months for 2 years after the last patient has enrolled in the study regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up.)

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient has a confirmed diagnosis of a select solid tumor (except for primary diagnosis of pancreatic cancer, biliary cancer, colorectal cancer, low grade serous ovarian cancer, melanoma) or hematologic malignancy (except for primary diagnosis of chronic myelomonocytic leukemia).
• Patients must be pre-identified as having a tumor with a mutation in RAF, RAS, NF1 or MEK at a CLIA certified laboratory
• Patient must have received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
• Patient must have progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion criteria

• Patient has received prior treatment with MEK162.
• Patients with primary CNS tumor or CNS tumor involvement
• History of retinal degenerative disease
• History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO)
• Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist
• Patients who have neuromuscular disorders that are associated with elevated CK

Trial design

110 participants in 1 patient group

MEK162

Experimental group

Description:

MEK162 will be dosed on a flat scale of 45 mg twice daily on a continuous dosing schedule.

Treatment:

Drug: MEK162