Primary Objective: Part A - Monotherapy: \- To determine the maximum tolerated dose (MTD) of SAR260301 administered as monotherapy and either on a once or twice daily schedule, to patients with advanced solid tumors or lymphomas. Part B - Combination: \- To determine the maximum tolerated dose (MTD) of SAR260301 administered in combination with the recommended standard dosage of vemurafenib to patients with unresectable / metastatic v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutated melanoma. Secondary Objectives: * To characterize the overall safety and tolerability profile of SAR260301 administered as monotherapy (Part A) and in combination with vemurafenib (Part B). * To characterize the pharmacokinetic (PK) profile of SAR260301 administered as monotherapy (Part A) and in combination with vemurafenib (Part B) as well as vemurafenib PK in combination with SAR260301 (Part B) * To evaluate food effect on SAR260301 PK (Part A) * To assess preliminary antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria). * To assess preliminary antitumor activity using volumetric computed tomography (CT) or magnetic resonance imaging(MRI) * To evaluate the pharmacodynamic (PD) effects of SAR260301 on blood and tumor. * To evaluate PK/PD relationships. * To identify the recommended phase 2 dose of SAR260301 in combination with vemurafenib (RP2D) (Part B only) * To assess potential induction effect of SAR260301 on cytochrome P450 (CYP) isoenzyme 3A (CYP3A) (Part A)
Study duration for one patient will include a period for inclusion (screening period) of up to 4 weeks, a treatment period of at least 4 weeks, and a end-of-study visit at 30 days following the last administration of study drug. The patient may continue treatment until disease progression, unacceptable toxicity or willingness to stop, followed by a minimum of 30-days follow-up.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
75
Pharmaceutical form: film-coated tablets Route of administration: oral
Pharmaceutical form: film-coated tablets Route of administration: oral
Investigational Site Number 840001
Boston, Massachusetts, United States
Investigational Site Number 840101
Boston, Massachusetts, United States
Investigational Site Number 840002
Houston, Texas, United States
Investigational Site Number 124001
Toronto, Canada
Maximal tolerated dose (MTD) of SAR260301 in monotherapy (Study Part A)
Time frame: Day 28
Maximal tolerated dose (MTD) of SAR260301 in combination with vemurafenib (Study Part B)
Time frame: Day 28
Number of patients with treatment emergent events
Time frame: Up to 2 years
Assessment of PK parameters for SAR260301 and vemurafenib, including tmax, Cmax, AUC, Rac (Day 28/Day1), half-life, CL, Ctrough
Time frame: 4 weeks
Assessment of PK parameters for SAR260301 including tmax, Cmax, AUC fasting and fed (food effect)(Only part A)
Time frame: Up to 8 weeks
Assessment of urine excretion of SAR2690301 (Part A)
Time frame: 12-24 hours at Day 28
Assessment of potential for CYP induction (4beta-hydroxycholesterol)(Part A)
Time frame: Up to 15 days
Assessment of PK parameter Rac (Day 28/Day 1) on AUC and Cmax
Time frame: 4 weeks
Assessment of PD parameter Serine/threonine protein kinase Akt (AKT) phosphorylation in blood platelets
Time frame: 4 weeks
Assessment of PD parameter AKT phosphorylation in tumor (expansion phase only)
Time frame: 15 days
Assessment of preliminary antitumor activity as documented by tumor response (defined by RECIST1.1 criteria for solid tumors, international working group (IWG) and revised response for lymphomas, and tumor markers when relevant)
Time frame: Up to 2 years
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