Advanced Solid Tumors, Metastatic Solid Tumors
Conditions
Keywords
BGJ398, BYL719, advanced solid tumor, metastatic breast cancer, PK3CA, FGFR, fibroblast growth factor receptor
Brief summary
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
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.
Interventions
DRUGBGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle.
DRUGBYL719
BYL719 will be administered orally once daily on each day of the 28-day cycle.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of BGJ398/BYL719 combination at the recommended dose for expansion (RDE) | 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 |
| Overall response rate | 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 |
| Progression free survival | Every two months from the date of baseline CT scan | Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719 |
| Time vs. concentration profile of BGJ398 and BYL719 | 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 |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Singapore, South Korea, Spain, Switzerland, United States
Outcome results
None listed