Phase 1b Trial of BGJ398/BYL719 in Solid Tumors

December 6, 2020 updated by: Novartis Pharmaceuticals

A Phase Ib, Open-label Study of Oral BGJ398 in Combination With Oral BYL719 in Adult Patients With Select Advanced Solid Tumors

To study the safety and efficacy of the combination of BGJ398 with BYL719 in patients whose tumors express mutations to PIK3CA with or without alterations to FGFR 1-3.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This dose escalation/dose expansion study will evaluate the combination of orally administered BGJ398 in combination with orally administered BYL719. During the dose escalation part, the MTD of the combination will be determined in patients whose advanced or metastatic tumors express mutations to PIK3CA. Once the MTD has been determined, the expansion part will begin. Patients will be addd to one of three arms based on the disease type and genetic changes. Patients with metastatic colorectal cancer are not eligible for participation in the expansion part.

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3050
        • Novartis Investigative Site
  • Belgium
      • Bruxelles, Belgium, 1200
        • Novartis Investigative Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
  • France
      • Lyon Cedex, France, 69373
        • Novartis Investigative Site
      • Saint Herblain cedex, France, 44805
        • Novartis Investigative Site
  • Germany
    • Nordrhein-Westfalen
      • Koeln, Nordrhein-Westfalen, Germany, 50937
        • Novartis Investigative Site
  • Italy
    • MI
      • Milano, MI, Italy, 20141
        • Novartis Investigative Site
    • MO
      • Modena, MO, Italy, 41100
        • Novartis Investigative Site
  • Korea, Republic of
    • Korea
      • Seoul, Korea, Korea, Republic of, 05505
        • Novartis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 169610
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28050
        • Novartis Investigative Site
    • Andalucia
      • Sevilla, Andalucia, Spain, 41013
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
  • Switzerland
      • Bellinzona, Switzerland, 6500
        • Novartis Investigative Site
  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute Moffitt 4
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0944
        • University of Michigan Comprehensive Cancer Center SC
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute Dept of Onc
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine Onc Dept
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center Onc Dept
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center Dept of Onc
    • Texas
      • San Antonio, Texas, United States, 78229
        • Cancer Therapy & Research Center / UT Health Science Center SC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 or metastatic solid tumors who have failed standard therapy or for whom no effective standard anti-cancer therapy exists
  • Documented PIK3CA mutations in all patients in dose escalation and expansion with or without documented genetic alterations in FGFR depending upon dose expansion cohort (either local or central determination)
  • Measurable disease defined by RECIST v1.1
  • ECOG performance status of ≤2

Exclusion Criteria:

  • Prior PI3Ki or selective FGFR inhibitor treatment (for patients enrolled to expansion part)
  • Colorectal cancer (for patients enrolled to expansion part)
  • Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting glucose ≥ 140 mg/dL / 7.8 mmol/L, history of clinically significant gestational diabetes mellitus or documented steroid-induced diabetes mellitus
  • Use of medications that increase serum levels of phosphorus and/or calcium
  • Inorganic phosphorus outside of normal limits
  • Total and ionized serum calcium outside of normal limits

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Metastatic breast cancer
Evaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3.
Drug: BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle.
Drug: BYL719
BYL719 will be administered orally once daily on each day of the 28-day cycle.
Experimental: Solid tumor arm 1
Patients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA.
Drug: BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle.
Drug: BYL719
BYL719 will be administered orally once daily on each day of the 28-day cycle.
Experimental: Solid tumor arm 2
Patients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3
Drug: BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle.
Drug: BYL719
BYL719 will be administered orally once daily on each day of the 28-day cycle.
Experimental: Dose escalation
To determine the MTD or RDE of the combination of BGJ398 with BYL719 in patients with advanced or metastastic solid tumors that express mutations to PIK3CA.
Drug: BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle.
Drug: BYL719
BYL719 will be administered orally once daily on each day of the 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719
Time Frame: Approximately 8 months
The dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or the recommended dose for expansion (RDE). Safety(incidence and nature of DLTs), pharmacokinetic and pharmacodynamic data will guide dose escalation decisioins.
Approximately 8 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of BGJ398/BYL719 combination at the recommended dose for expansion (RDE)
Time Frame: Every 28 days from baseline visit until end of study visit
This will be assessed by looking at the number of Adverse Events (AEs), serious AEs (SAEs) changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions and reductions
Every 28 days from baseline visit until end of study visit
Overall response rate
Time Frame: Every two months from the date of baseline CT scan
Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719; Overall response rate = complete response + partial response
Every two months from the date of baseline CT scan
Progression free survival
Time Frame: Every two months from the date of baseline CT scan
Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719
Every two months from the date of baseline CT scan
Time vs. concentration profile of BGJ398 and BYL719
Time Frame: Every 28 days for up to 10 cycles
Plasma concentration versus time profiles. Plasma PK parameters will be used to characterize the PK profiles of the combination of BGJ398 with BYL719
Every 28 days for up to 10 cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2013

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

August 21, 2013

First Submitted That Met QC Criteria

August 21, 2013

First Posted (Estimate)

August 26, 2013

Study Record Updates

Last Update Posted (Actual)

December 9, 2020

Last Update Submitted That Met QC Criteria

December 6, 2020

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CBGJ398X2102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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