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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

139

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Mar 2012

Longer than P75 for phase_1

Geographic Reach

7 countries

16 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.5 years study duration

First Submitted

Initial submission to the registry

October 6, 2011

Completed

1 day until next milestone

First Posted

Study publicly available on registry

October 7, 2011

Completed

5 months until next milestone

Study Start

First participant enrolled

March 1, 2012

Completed

4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2016

Completed

12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2017

Completed

Last Updated

October 2, 2017

Status Verified

September 1, 2017

Enrollment Period

4.5 years

First QC Date

October 6, 2011

Last Update Submit

September 29, 2017

Conditions

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

Keywords

Advanced solid tumor,AMLhigh risk and very high risk MDSdose escalation,RAS/BRAF mutation,PI3K inhibitor,MEK inhibitor,BYL719,MEK162

Outcome Measures

Primary Outcomes (1)

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 Outcomes (7)

Number of participants with adverse events and serious adverse events
Assessed from Cycle 1 Day 1 until treatment discontinuation
Overall response rate
Assessed every 8 weeks until disease progression
Time to progression
Assessed every 8 weeks until disease progression
Progression free survival
Assessed every 8 weeks until disease progression
Time versus plasma concentration profiles of BYL719 and MEK162
Assessed during the first cycle of treatment
+2 more secondary outcomes

Study Arms (1)

BYL719 + MEK162

EXPERIMENTAL

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

Drug: BYL719Drug: MEK162

Interventions

BYL719DRUG

taken orally

BYL719 + MEK162

MEK162DRUG

taken orally

BYL719 + MEK162

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Histologically/cytologically confirmed, advanced solid tumors, AML or high risk and very high risk MDS
Measurable disease as determined by RECIST 1.1

You may not qualify if:

Primary CNS tumor or CNS tumor involvement
Diabetes mellitus
Unacceptable ocular/retinal conditions
Clinically significant cardiac disease or impaired cardiac function

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Array BioPharmalead

Study Sites (16)

University of California San Diego - Moores Cancer Center Dept Onc

La Jolla, California, 92093-0658, United States

Location

H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC

Tampa, Florida, 33612, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital CCPO

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center Onc. Dept

New York, New York, 90033, United States

Location

Montefiore Medical Center SC

The Bronx, New York, 10461, United States

Location

University of Texas/MD Anderson Cancer Center Dept. of Onc.

Houston, Texas, 77030-4009, United States

Location

University of Utah / Huntsman Cancer Institute Huntsman (3)

Salt Lake City, Utah, 84103, United States

Location