This trial is active, not recruiting.

Condition advanced and selected solid tumors, aml, high risk and very high risk mds
Treatment byl719 plus mek162
Phase phase 1/phase 2
Targets MEK, PI3K
Sponsor Array BioPharma
Start date March 2012
End date August 2016
Trial size 138 participants
Trial identifier NCT01449058, 2011-002578-21, CMEK162X2109


This is a multi-center, open-label, dose-finding, phase Ib study to estimate the maximum tolerated dose(s) (MTD(s)) and/or recommended dose(s) for expansion (RDE(s)) for the orally administered combination of BYL719 and MEK162. This combination will be explored in adult patients with advanced CRC, esophageal cancer, pancreatic cancer, NSCLC, ovarian cancer, or other advanced solid tumors and in adult patients with AML or high risk and very high risk MDS, with documented RAS or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RDE, four expansion arms will be opened in order to further assess the safety and preliminary activity of the combination of BYL719 and MEK162 in specific patient populations.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
BYL719 plus MEK162. Dose escalation with a starting dose for the first cohort of 200mg QD BYL719 and 30mg BID MEK162
byl719 plus mek162
BYL719 plus MEK162 administered in this dose escalation study until MTD/RDE is achieved, followed by a dose expansion phase.

Primary Outcomes

Incidence of Dose Limiting Toxicities (DLT)
time frame: during the first cycle (28 days) of treatment with BYL719 and MEK162

Secondary Outcomes

Number of participants with adverse events and serious adverse events
time frame: Assessed from Cycle 1 Day 1 until treatment discontinuation
Overall response rate
time frame: Assessed every 8 weeks until disease progression
Time to progression
time frame: Assessed every 8 weeks until disease progression
Progression free survival
time frame: Assessed every 8 weeks until disease progression
Time versus plasma concentration profiles of BYL719 and MEK162
time frame: Assessed during the first cycle of treatment
Correlation of baseline mutation or amplification status (PIK3CA, KRAS, NRAS and BRAF) and clinical anti-tumor activity outcome
time frame: Assessed at Baseline (pre-treatment)
Clinical benefit rate
time frame: Assessed every 4 weeks for 3 months and every 3 months for 6 months followed by every 6 months thereafter until disease progression

Eligibility Criteria

All participants at least 18 years old.

Inclusion Criteria: - Histologically/cytologically confirmed, advanced solid tumors, AML or high risk and very high risk MDS - Measurable disease as determined by RECIST 1.1 Exclusion Criteria: - Primary CNS tumor or CNS tumor involvement - Diabetes mellitus - Unacceptable ocular/retinal conditions - Clinically significant cardiac disease or impaired cardiac function

Additional Information

Official title A Phase Ib Open-label, Multi-center, Dose Escalation and Expansion Study of Orally Administered MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Array BioPharma.