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

AML Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01449058
• Other study ID #: CMEK162X2109
• Secondary ID: 2011-002578-21
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2011
• Last updated: September 29, 2017
• Start date: March 2012
• Est. completion date: August 15, 2017

Study information

• Verified date: September 2017
• Source: Array BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: August 15, 2017
• Est. primary completion date: August 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced and Selected Solid Tumors
• AML
• High Risk and Very High Risk MDS

Intervention

Drug:
• BYL719
taken orally
• MEK162
taken orally

Locations

Country	Name	City	State
Australia	Array BioPharma Investigative Site	Parkville	Victoria
France	Array BioPharma Investigative Site	Villejuif Cedex
Italy	Array BioPharma Investigative Site	Milano	MI
Italy	Array BioPharma Investigative Site	Roma	RM
Spain	Array BioPharma Investigative Site	Barcelona	Catalunya
Spain	Array BioPharma Investigative Site	Barcelona	Catalunya
Switzerland	Array BioPharma Investigative Site	Bellinzona
United Kingdom	Array BioPharma Investigative Site	Sutton
United States	Massachusetts General Hospital CCPO	Boston	Massachusetts
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Texas/MD Anderson Cancer Center Dept. of Onc.	Houston	Texas
United States	University of California San Diego - Moores Cancer Center Dept Onc	La Jolla	California
United States	Memorial Sloan Kettering Cancer Center Onc. Dept	New York	New York
United States	University of Utah / Huntsman Cancer Institute Huntsman (3)	Salt Lake City	Utah
United States	H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC	Tampa	Florida
United States	Montefiore Medical Center SC	The Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
Array BioPharma

Countries where clinical trial is conducted

United States,  Australia,  France,  Italy,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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