Ph Ib/BGJ398/Cervix and Other Solid Tumors
Ph Ib/BGJ398/Cervix and Other Solid Tumors
This study will be conducted using 3+3 design and includes, a dose escalation part to define
 the MTDfRP2D for the combination of BGJ398 and carboplatin/paclitaxel, and a dose expansion
 part to treat another 12 patients (only cervix cancer) to further evaluate safety of this
 combination. Safety, tolerability and MTD will be determined in the dose escalation part of
 the study. The dose expansion will additionally investigate preliminary anti-tumor efficacy
 in cervical cancer. The dosing cycle is 21 days.
Inclusion Criteria:

 -  Male or female subjects age >18 years at the time of informed consent

 -  Histologically/cytologically confirmed locally advanced or metastatic solid tumors for
 which no curable therapy exists. In dose expansion part of this study, only patients
 with stage IV or recurrent/persistent cervical cancer will be enrolled. Confirmation
 of FGF/FGFR aberration is not required.

 -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

 -  Adequate marrow function as defined below:

 absolute neutrophil count ≥ 1.5 x 10 9/L platelets ≥ 100,000 x 10 9/L hemoglobin ≥ 9.0 g/dL
 Adequate liver function as evidenced by bilirubin <1.5 times the upper limit of normal
 (ULN); alanine aminotransferase (AL T) and aspartate aminotransferase (AST) <3 times the
 ULN

 -  Evidence of measurable or evaluable disease, as determined by RECIST v 1.1

 -  Women of child-bearing potential and men must agree to use adequate contraception
 (hormonal or barrier method of birth control; abstinence) prior to study entry, for
 the duration of study participation, and for 90 days following completion of therapy.
 Should a woman become pregnant or suspect she is pregnant while participating in this
 study, she should inform her treating physician immediately. A female of child-bearing
 potential is any woman (regardless of sexual orientation, having undergone a tubal
 ligation, or remaining celibate by choice) who meets the following criteria: has not
 undergone a hysterectomy or bilateral oophorectomy, or has not been naturally
 postmenopausal for at least 12 consecutive months (Le., has had menses at any time in
 the preceding 12 consecutive months). Oral contraceptives (OC), injected or implanted
 hormonal methods are not allowed as the sole method of contraception because BGJ398
 has not been characterized with respect to its potential to interfere with PK and/or
 the effectiveness of OCs.

 -  It is preferred that archival tumor sample is available for molecular testing, if not
 available, a newly obtained tumor biopsy may be submitted instead (not mandatory)

 Exclusion Criteria:

 -  For patients enrolled in dose escalation, any number of prior treatments allowed. For
 patients enrolled in dose expansion, no prior chemotherapy is allowed (previous single
 agent cisplatin concurrent with radiotherapy is accepted).

 -  No prior therapy with paclitaxel, BGJ398 or other FGFR targeting agents.

 -  Preexisting> grade 2 peripheral neuropathy

 -  Patients with brain metastases are allowed provided that they are clinically stable
 for a period of 30 days prior to study entry and there is not a requirement for
 steroids or anti epileptics.

 -  History of pancreatitis in last 6 months prior to enrollment.

 -  History and/or current evidence of endocrine alterations of calcium/phosphate
 homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis,
 tumoral calcinosis, or patients with other phosphate regulating abnormalities. Because
 hyperphosphatemia is a frequent occurrence with BGJ398 treatment, pretreatment and
 concurrent treatment with phosphate regulating agents is allowed.

 -  Current evidence of corneal or retinal disorder/ keratopathy such as bullous/ band
 keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivits, etc

 -  Since BGJ398 is a likely inhibitor of CYP3A4, patients who are currently receiving
 treatment with agents that are known sting inducers or inhibitors CYP3A4 are not
 allowed

 -  Treatment with any of the following anti-cancer therapies prior to the first dose of
 the of BGJ398 within the stated timeframes: intravenous chemotherapy within a period
 of 4 weeks ( 6 weeks for nitrosourea, mitomycin-C), biological therapy (e,g.
 antibodies) within a period of time that is ~ 5 t1/2 or less than 4 weeks, whichever
 is shorter, prior to starting study drug, any other investigational agents within a
 period of time that is < 5 tl/2 or 4 weeks (whichever is shortest) prior to starting
 study drug, wide field radiotherapy < 4 weeks or limited field radiation for
 palliation < 2 weeks prior to starting study drug.

 -  Use of medications that increase serum levels of phosphorus and/or calcium.

 -  History of cardiac disease (Congestive heart failure NYHA grade> 2, LVEF < 50% as
 determined by MUGA scan or ECHO, history of clinically significant ventricular
 arrhythmias, unstable angina pectoriS or acute myocardial infarction <6 months prior
 to starting study drug, QTcF > 450 msec)

 -  Pregnant or nursing (lactating) women.