Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 3 - MEK162 for Patients With RAS/RAF/MEK Activated Tumors
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.)
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical benefit rate associated with MEK162 treatment
Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of CR or PR or SD. For hematologic tumors other appropriate hematological response criteria will apply
United States: Food and Drug Administration