Safety, Pharmacokinetics and Pharmacodynamics of BEZ235 Plus MEK162 in Selected Advanced Solid Tumor Patients

A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BEZ235 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors

This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or RP2D of the orally administered PI3K/mTOR inhibitor BEZ235 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with EGFR mutant NSCLC which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BEZ235 and MEK162.

Study drugs will be administered orally on a continuous schedule, MEK162 bid and BEZ235 qd, a treatment cycle is defined as 28 days.

Study Overview

• Status: Completed
• Conditions: Solid Tumor; Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: BEZ235 + MEK162

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Pfizer Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Pfizer Investigative Site
• France
  • Villejuif Cedex, France, 94805
    • Pfizer Investigative Site
• Spain
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Pfizer Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Mass General 2
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas/MD Anderson Cancer Center MD Anderson PSC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• histologically/cytologically confirmed, advanced non resectable solid tumors
• Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0

Exclusion Criteria:

• Patients with primary CNS tumor or CNS tumor involvement
• Diabetes mellitus - Unacceptable ocular/retinal conditions

Other protocol-defined inclusion/exclusion criteria may apply

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: BEZ235 + MEK162	Drug: BEZ235 + MEK162

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicities	A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination	during Cycle 1 of treatment with BEZ235 and MEK162

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate, duration of response, time to response and progression free survival		every 8 weeks of treatment
Number of participants with adverse events and serious adverse events	A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination	from Cycle 1 Day 1 until treatment discontinuation
Time versus plasma concentration profiles of BEZ235 and MEK162	A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination	during the first cycle of treatment
Treatment-induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor	A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination	during the first cycle of treatment and at disease progression

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2011
• Primary Completion (Actual): March 22, 2013
• Study Completion (Actual): March 22, 2013

Study Registration Dates

• First Submitted: April 2, 2011
• First Submitted That Met QC Criteria: April 15, 2011
• First Posted (Estimate): April 19, 2011

Study Record Updates

• Last Update Posted (Actual): October 9, 2020
• Last Update Submitted That Met QC Criteria: October 7, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: MEK inhibitor; MEK162; triple negative breast cancer; RAS RAF mutations,; pancreatic cancer,; NSCLC progressed on EGFR TKI; BEZ235,; PI3K/mTOR inhibitor,; Advanced and selected solid tumors
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Dactolisib
• Other Study ID Numbers: CMEK162X2103; 2011-000421-74 (EudraCT Number); C4211009 (Other Identifier: Pfizer)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.