Oral SAR245408 (XL147) and Oral MSC1936369B in Patients With Locally Advanced or Metastatic Solid Tumors
Oral SAR245408 (XL147) and Oral MSC1936369B in Patients With Locally Advanced or Metastatic Solid Tumors
Primary Objective:

 - To determine the maximum tolerated dose(s) (MTD) and the recommended Phase 2 dose(s) (RP2D)
 of SAR245408 and MSC1936369B when combined in adult subjects with locally advanced or
 metastatic solid tumors.

 Secondary Objective:

 -  To characterize the safety and tolerability of SAR245408 and MSC1936369B combination
 therapy administered orally to adult patients with locally advanced or metastatic solid
 tumors

 -  To evaluate the pharmacokinetic (PK) profile of SAR245408 and MSC1936369B when used in
 combination

 -  To evaluate the pharmacodynamic (PD) effect of the SAR245408/MSC1936369B combination by
 assessing target and pathway inhibition
The duration of the study will include a period for screening of up to a maximum of 28 days,
 a pretreatment evaluation period of up to 5 days, the on-treatment period, followed by a
 minimum of 30-day follow-up after the last study drug administration.

 The patient may continue study treatment until disease progression, unacceptable toxicity, or
 consent withdrawal.

 The study will have 2 parts:

 -  Part one - Dose Escalation

 -  Part Two - Expansion. At the defined maximum tolerated doses (MTD(s), additional
 patients will be enrolled to collect safety, Pharmacokinetic, and Pharmacodynamic data
Inclusion criteria:

 Patient with advanced solid tumors for which there is no approved or curative therapy:

 -  has any advanced solid tumor with diagnosed alteration in 1 or more genes of the PI3K,
 and mitogen-activated protein kinase (MAPK) pathways and/or

 -  has a histologically or cytologically confirmed diagnosis of 1 of the following solid
 tumors: pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal,
 breast, ovarian carcinoma and melanoma

 Exclusion criteria:

 The patient has previously been treated with a PI3K inhibitor or a Mitogen-activated
 protein extracellular signal-regulated kinase (MEK) inhibitor

 The patient has received:

 -  Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other
 anticancer therapy within 28 days or 5 half lives for noncytotoxics (whichever is
 shorter) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin C)

 -  Any investigational agent within 28 days of Day 1 of trial drug treatment The patient
 is currently receiving anticoagulation therapy with therapeutic doses of warfarin
 (low-dose warfarin ≤1 mg/day, heparin, and low-molecular weight heparins are
 permitted) History of central nervous system metastases The patient has had congestive
 heart failure, unstable angina, a myocardial infarction, cardiac conduction
 abnormality or pacemaker or a stroke within 3 months of entering the study. The
 patient has retinal degenerative disease (hereditary retinal degeneration or
 age-related macular degeneration), history of uveitis, or history of retinal vein
 occlusion, or has medically relevant abnormalities identified on screening
 ophthalmologic examination.

 The above information is not intended to contain all considerations relevant to a patient's
 potential participation in a clinical trial.