A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors

Phase 1

Completed

• Conditions: Advanced and Selected Solid Tumors; AML; High Risk and Very High Risk MDS
• Interventions: Drug: BYL719; Drug: MEK162

• Registration Number: NCT01449058
• Lead Sponsor: Array BioPharma

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-10-06
• Study First Submitted QC: 2011-10-06
• Study First Posted: 2011-10-07
• Study Start: 2012-03
• Primary Completion: 2016-08-31
• Study Completion: 2017-08-15
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-29
• Last Update Posted: 2017-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 139

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BYL719 + MEK162	MEK162	BYL719 plus MEK162. Dose escalation with a starting dose for the first cohort of 200mg QD BYL719 and 30mg BID MEK162
BYL719 + MEK162	BYL719	BYL719 plus MEK162. Dose escalation with a starting dose for the first cohort of 200mg QD BYL719 and 30mg BID MEK162

Primary Outcome Measures

Name	Time	Method
Incidence of Dose Limiting Toxicities (DLT)	during the first cycle (28 days) of treatment with BYL719 and MEK162	Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 unless otherwise specified. A DLT is defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤ 28 days following the first dose of BYL719 and MEK162 (Cycle 1), and meets any of the protocol-specified DLT criteria.

Secondary Outcome Measures

Name	Time	Method
Progression free survival	Assessed every 8 weeks until disease progression	Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
Number of participants with adverse events and serious adverse events	Assessed from Cycle 1 Day 1 until treatment discontinuation	All AEs and SAEs will be collected in accordance with the protocol and assessed for relatedness to study drug combination.
Overall response rate	Assessed every 8 weeks until disease progression	Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR).
Correlation of baseline mutation or amplification status (PIK3CA, KRAS, NRAS and BRAF) and clinical anti-tumor activity outcome	Assessed at Baseline (pre-treatment)	Collect baseline genetic mutation/alteration status to investigate the potential relationship to anti-tumor activity.
Time to progression	Assessed every 8 weeks until disease progression	Time to progression (TTP) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient has not had an event, time to progression is censored at the date of last adequate tumor assessment.
Time versus plasma concentration profiles of BYL719 and MEK162	Assessed during the first cycle of treatment	Blood concentrations of MEK162 and its metabolite (AR00426032) and BYL719 will be assessed during the first cycle of treatment.
Clinical benefit rate	Assessed every 4 weeks for 3 months and every 3 months for 6 months followed by every 6 months thereafter until disease progression	The clinical benefit rate is defined as the proportion of patients with complete remission, complete remission with incomplete blood count recovery, partial remission, minor response or stable disease for \> 15 weeks

Trial Locations

Locations (9)

H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC; 🇺🇸 Tampa, Florida, United States

Montefiore Medical Center SC; 🇺🇸 The Bronx, New York, United States

Memorial Sloan Kettering Cancer Center Onc. Dept; 🇺🇸 New York, New York, United States

Massachusetts General Hospital CCPO; 🇺🇸 Boston, Massachusetts, United States

University of Texas/MD Anderson Cancer Center Dept. of Onc.; 🇺🇸 Houston, Texas, United States

Array BioPharma Investigative Site; 🇬🇧 Sutton, United Kingdom

University of California San Diego - Moores Cancer Center Dept Onc; 🇺🇸 La Jolla, California, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

University of Utah / Huntsman Cancer Institute Huntsman (3); 🇺🇸 Salt Lake City, Utah, United States