Phase 1b Trial of BGJ398/BYL719 in Solid Tumors

Novartis

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors; Metastatic Solid Tumors

Treatments: Drug: BYL719; Drug: BGJ398

Study type: Interventional

Funder types: Industry

Identifiers

NCT01928459

CBGJ398X2102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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62 participants in 4 patient groups

Metastatic breast cancer

Experimental group

Description:

Evaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3.

Treatment:

Drug: BGJ398

Drug: BYL719

Solid tumor arm 1

Experimental group

Description:

Patients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA.

Treatment:

Drug: BGJ398

Drug: BYL719

Solid tumor arm 2

Experimental group

Description:

Patients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3

Treatment:

Drug: BGJ398

Drug: BYL719

Dose escalation

Experimental group

Description:

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.

Treatment:

Drug: BGJ398

Drug: BYL719