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

Sponsor

Array BioPharma (Industry)

Overall Status

Completed

CT.gov ID

NCT01449058

Collaborator

(none)

139

Enrollment

Locations

Arm

65.5

Duration (Months)

8.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced and Selected Solid Tumors AML High Risk and Very High Risk MDS	Drug: BYL719 Drug: MEK162	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

139 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Aug 31, 2016

Actual Study Completion Date :

Aug 15, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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).
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.
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.
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.
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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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