A phase Ib, open-label study of oral BGJ398 in combination with oral BYL719 in adult patients with select advanced solid tumors

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 2

Inclusion Criteria

* Histologically/cytologically confirmed advanced or metastatic solid tumors who have failed standard therapy or for whom no effective standard anticancer 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) ;* Ongoing grade 2 or greater sequelae from previous systemic anti-cancer therapies, except for:
alopecia and stable neuropathy of * grade 2 ;* History and/or current evidence of tissue calcification;* Patients with diabetes mellitus requiring insulin treatment or with fasting glucose * 140 mg/dL / 7.8 mmol/L, ;* Known acute or chronic pancreatitis;* Treatment with chronic systemic corticosteroids * 2 weeks prior to starting study drug,
* Impairment of gastrointestinal tract function or GI disease that may significantly alter the absorption of BGJ398 or BYL719;* History and/or current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis etc;* Confirmed evidence of corneal or retinal disorder;* Treatment with agents that are known strong inducers or inhibitors CYP3A4 are prohibited. ;* Insufficient bone marrow function:
-ANC <1,000/mm3 [1.0 x 109/L]
-Platelets < 75,000/mm3 [75 x 109/L]
-Hemoglobin < 9.0 g/dL;* Insufficient hepatic and renal function
-Total bilirubin > 1.5x ULN
-AST/SGOT or ALT/SGPT > 3x ULN (AST or ALT > 5x ULN in the presence of liver metastases)
-Serum creatinine > ULN
-Calculated or measured creatinine clearance < 75% LLN;* Calcium-phosphate homeostasis
-Inorganic phosphorus outside of normal limits
-Total and ionized serum calcium outside of normal limits;* Clinically significant cardiac disease including any of the following:
- Congestive heart failure requiring treatment (NYHA grade * 2),
- LVEF < 50% (MUGA or ECHO),
- History or presence of clinically significant ventricular arrhythmias, atrial fibrillation, resting bradycardia, or conduction abnormality,
- Unstable angina pectoris or acute myocardial infarction * 3 months prior to starting study drug,
- QTcF > 450 msec, history of congenital long QT syndrome

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of the study, MTD and/or RDE, is measured by incidence of<br /><br>DLTs in cycle 1.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* Incidence and severity of adverse events and serious adverse events, changes<br /><br>in laboratory values, electrocardiograms and vital signs. Dose interruptions,<br /><br>reductions and dose intensity.<br /><br>* Time vs. concentration profiles, derived PK parameters of BGJ398 and BYL719<br /><br>and known active metabolites.<br /><br>* Overall response rate (ORR; CR+PR) assessed by investigators per RECIST and<br /><br>progression free survival.</p><br>