Primary Objectives: To determine the maximum tolerated dose (MTD) of SAR125844. To confirm safety profile of SAR125844 when administered as single agent at the MTD. To evaluate the preliminary anti-tumoral effect of SAR125844 in patients with MET-gene amplified solid tumors (including sub-group of MET-amplified non-small cell lung cancer \[NSCLC\] patients) and in patients with Phospho-MET positive tumors without MET-gene amplification. Secondary Objectives: To characterize the global safety profile including cumulative toxicities. To evaluate the pharmacokinetic profile of SAR125844 in the proposed dosing schedule(s). To assess preliminary antitumor activity in patients with measurable/evaluable disease, according to RECIST 1.1 criteria. To explore the pharmacodynamic effects (PD) of SAR125844. To explore MET gene amplification status in Circulating Tumoral Cells (CTCs) and on tumor biopsies collected during the study, in the escalation part only. To evaluate other pharmacodynamic biomarkers and help selection of patients who could benefit from SAR125844. To explore MET-gene amplification status in circulating DNA.
The duration of the study for one patient in the dose escalation phase of the study will include a screening period of up to 3 weeks and a 4-week treatment cycle(s). The patients may continue treatment until disease progression, unacceptable toxicity, or willingness to stop, followed by a minimum of 30-day follow-up. The study will also include 2 expansion cohorts. If a patient treated in dose escalation part or in an expansion cohorts, continues to benefit from the treatment at the time of Clinical Study Report, the patient can continue study treatment for a maximum of 1 year and will continue to undergo all assessments as per the study flowchart. Such patients will be followed at least until 30 days after the last IMP administration.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Masking
NONE
Enrollment
72
Pharmaceutical form:solution Route of administration: intravenous
Investigational Site Number 840001
Boston, Massachusetts, United States
Investigational Site Number 250002
Dijon, France
Investigational Site Number 250001
Villejuif, France
Investigational Site Number 380004
Bologna, Italy
Investigational Site Number 380002
Milan, Italy
Investigational Site Number 380001
Milan, Italy
Investigational Site Number 724001
Barcelona, Spain
Investigational Site Number 724003
Madrid, Spain
Dose Escalation To determine the maximum tolerated dose (MTD) of SAR125844
Time frame: At day 28 of Cycle 1 of each treated patient, DLT is assessed
Expansion Cohorts To evaluate the preliminary anti-tumoral effect of SAR125844
Time frame: Anticancer activity is assessed at Day 28 and then every 8 weeks thereafter up to an expected maximum of 2 years
Number of patients with treatment emergent events
Time frame: Up to 2 years
Assessment of PK parameter Cmax
Time frame: Up to 2 years
Assessment of PK parameter AUCs
Time frame: Up to 2 years
Assessment of PK parameter CL
Time frame: Up to 2 years
Assessment of PD parameter ShedMET
Time frame: Up to 2 years
Assessment of PD parameter HGF
Time frame: Up to 2 years
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