Phase 1b Trial of BGJ398/BYL719 in Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Advanced Solid Tumors, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: BGJ398
* Drug: BYL719


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719 | 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) | 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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BGJ398, BYL719, advanced solid tumor, metastatic breast cancer, PK3CA, FGFR, fibroblast growth factor receptor