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.
Brief Title
A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
Completion Date
Completion Date Type
Actual
Conditions
Advanced and Selected Solid Tumors
AML
High Risk and Very High Risk MDS
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* Histologically/cytologically confirmed, advanced solid tumors, AML or high risk and very high risk MDS
* Measurable disease as determined by RECIST 1.1
Gender
All
Gender Based
false
Keywords
Advanced solid tumor,
AML
high risk and very high risk MDS
dose escalation,
RAS/BRAF mutation,
PI3K inhibitor,
MEK inhibitor,
BYL719,
MEK162
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01449058
Org Class
Industry
Org Full Name
Array BioPharma
Org Study Id
CMEK162X2109
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Incidence of Dose Limiting Toxicities (DLT)
Outcome Time Frame
during the first cycle (28 days) of treatment with BYL719 and MEK162
Secondary Ids
Secondary Id
2011-002578-21
Secondary Outcomes
Outcome Description
All AEs and SAEs will be collected in accordance with the protocol and assessed for relatedness to study drug combination.
Outcome Time Frame
Assessed from Cycle 1 Day 1 until treatment discontinuation
Outcome Measure
Number of participants with adverse events and serious adverse events
Outcome Description
Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR).
Outcome Time Frame
Assessed every 8 weeks until disease progression
Outcome Measure
Overall response rate
Outcome Description
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.
Outcome Time Frame
Assessed every 8 weeks until disease progression
Outcome Measure
Time to progression
Outcome Description
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.
Outcome Time Frame
Assessed every 8 weeks until disease progression
Outcome Measure
Progression free survival
Outcome Description
Blood concentrations of MEK162 and its metabolite (AR00426032) and BYL719 will be assessed during the first cycle of treatment.
Outcome Time Frame
Assessed during the first cycle of treatment
Outcome Measure
Time versus plasma concentration profiles of BYL719 and MEK162
Outcome Description
Collect baseline genetic mutation/alteration status to investigate the potential relationship to anti-tumor activity.
Outcome Time Frame
Assessed at Baseline (pre-treatment)
Outcome Measure
Correlation of baseline mutation or amplification status (PIK3CA, KRAS, NRAS and BRAF) and clinical anti-tumor activity outcome
Outcome Description
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
Outcome Time Frame
Assessed every 4 weeks for 3 months and every 3 months for 6 months followed by every 6 months thereafter until disease progression
Outcome Measure
Clinical benefit rate
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Kira Gritsman
Investigator Email
kira.gritsman@einsteinmed.org
Investigator Phone
929-246-6707
MeSH Terms
ALPELISIB
BINIMETINIB