A Phase 1b Dose-escalation Study of the Safety and Pharmacokinetics of SAR245408 Administered in Combination With SAR256212 in Patients With Solid Tumor Cancers
A Phase 1b Dose-escalation Study of the Safety and Pharmacokinetics of SAR245408 Administered in Combination With SAR256212 in Patients With Solid Tumor Cancers
Primary Objective:
Secondary Objectives:
There is a 28 day screening period followed by 28 day cycles (21 day cycle for the every three week dosing regimen, if used) . Patients will continue to receive SAR245408/SAR256212 as long as there is clinical benefit or until a study withdrawal criterion is met. The last posttreatment visit will be 60 days after the last dose or until IMP-related toxicities have resolved or are deemed irreversible, whichever is later.
Inclusion criteria:
Metastatic or locally advanced nonhematological cancer, for which no alternative therapy is available
Written informed consent
For dose expansion only:
Measurable and evaluable disease
Exclusion criteria:
Patient less than 18 years old
ECOG (Eastern Cooperative Oncology Group) performance status >2
Any serious active disease or comorbid condition, which, in the opinion of the Investigator, could interfere with the safety of the patient or the ability of the patient to comply with the study, or with the interpretation of the results
Poor bone marrow reserve as defined by absolute neutrophils count <1.5 x 109/L or platelets <100 x 109/L
Poor organ function as defined by 1 of the following:
Pregnant or breast-feeding women
No use of effective birth control methods, when applicable
No resolution of all specific toxicities (excluding alopecia) related to any prior anticancer therapy to Grade ≤1 according to the NCI common terminology criteria for adverse events (CTCAE) v.4.0
Any of the following within 6 months prior to enrollment: myocardial infarction, severe/unstable angina, or coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant cardiac arrhythmias (Grade 3/4)
Baseline corrected QT interval (QTc) >460 ms.
NYHA Class III (New York Heart Association) or IV congestive heart failure or LVEF (left ventricular ejection fraction) < the lower limit of normal (LLN) for institution
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including cytomegalovirus, Epstein-Barr virus, toxoplasmosis, and hepatitis B and C, positive for the human immunodeficiency virus (HIV), hypertension, or uncontrolled diabetes.
Previous treatment with a selective PI3K inhibitor (phosphoinositide-3-kinase, catalytic, alpha polypeptide), mTOR (mechanistic target of rapamycin) inhibitor, or AKT inhibitor (v-akt murine thymoma viral oncogene homolog 1)
Known hypersensitivity to the investigational medicinal product(s) or to its excipients, or patient who has had hypersensitivity reactions to fully human monoclonal antibodies
Cytotoxic chemotherapy (including investigational cytotoxic agents) or biologic agents (antibodies, immune modulators, cytokines) within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks, before the first dose of study treatment
Prior radiation therapy within 2 weeks before the first dose of study treatment
Prior major surgery from which the patient has not recovered or stabilized
Any other investigational therapy within 4 weeks prior to the first dose of study treatment
Brain tumor or brain metastasis are considered eligible if the patient has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for 2 or more weeks
Ongoing anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤1 mg/day is permitted).
HBA1C (hemoglobin A1c) >7 or any patient requiring medication for glycemic control
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.