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

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

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.

Study Overview

• Status: Completed
• Conditions: AML; Advanced and Selected Solid Tumors; High Risk and Very High Risk MDS
• Intervention / Treatment: Drug: BYL719; Drug: MEK162

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Array BioPharma Investigative Site
• France
  • Villejuif Cedex, France, 94805
    • Array BioPharma Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20133
      • Array BioPharma Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Array BioPharma Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Array BioPharma Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Array BioPharma Investigative Site
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Array BioPharma Investigative Site
• United Kingdom
  • Sutton, United Kingdom, SM2 5PT
    • Array BioPharma Investigative Site
• United States
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center Dept Onc
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital CCPO
  • New York
    • New York, New York, United States, 90033
      • Memorial Sloan Kettering Cancer Center Onc. Dept
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center SC
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas/MD Anderson Cancer Center Dept. of Onc.
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • University of Utah / Huntsman Cancer Institute Huntsman (3)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BYL719 + MEK162; BYL719 plus MEK162. Dose escalation with a starting dose for the first cohort of 200mg QD BYL719 and 30mg BID MEK162	Drug: BYL719; taken orally; Drug: MEK162; taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicities (DLT)	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.	during the first cycle (28 days) of treatment with BYL719 and MEK162

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events and serious adverse events	All AEs and SAEs will be collected in accordance with the protocol and assessed for relatedness to study drug combination.	Assessed from Cycle 1 Day 1 until treatment discontinuation
Overall response rate	Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR).	Assessed every 8 weeks until disease progression
Time to 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.	Assessed every 8 weeks until disease progression
Progression free survival	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.	Assessed every 8 weeks until disease progression
Time versus plasma concentration profiles of BYL719 and MEK162	Blood concentrations of MEK162 and its metabolite (AR00426032) and BYL719 will be assessed during the first cycle of treatment.	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	Collect baseline genetic mutation/alteration status to investigate the potential relationship to anti-tumor activity.	Assessed at Baseline (pre-treatment)
Clinical benefit rate	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	Assessed every 4 weeks for 3 months and every 3 months for 6 months followed by every 6 months thereafter until disease progression

Collaborators and Investigators

• Sponsor: Array BioPharma

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): August 31, 2016
• Study Completion (Actual): August 15, 2017

Study Registration Dates

• First Submitted: October 6, 2011
• First Submitted That Met QC Criteria: October 6, 2011
• First Posted (Estimate): October 7, 2011

Study Record Updates

• Last Update Posted (Actual): October 2, 2017
• Last Update Submitted That Met QC Criteria: September 29, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: AML; MEK162; dose escalation,; Advanced solid tumor,; high risk and very high risk MDS; RAS/BRAF mutation,; PI3K inhibitor,; MEK inhibitor,; BYL719,
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CMEK162X2109; 2011-002578-21 (EudraCT Number)