Advanced solid tumors
Conditions
Interventions
Part 1A:
SAR439459 administered intravenously every 2 weeks in a 14-day cycle with
escalating doses between 0.05 - 15 mg/kg
Part 1B:
SAR439459 + cemiplimab combination administered intravenously e
Sponsors
Genzyme Europe BV
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Dose escalation (Part 1A and Part 1B):, -Patients with histologically confirmed, advanced unresectable or metastatic solid tumor whom in the opinion of the Investigator does not have a suitable alternative therapy., Dose expansion (Part 2A):, -Patients with histologically confirmed, advanced unresectable melanoma whom in the opinion of the Investigator does not have a suitable alternative therapy -Patients must have failed any prior therapy based on anti-PD-1 or anti-PD-L1 as defined by disease progression within 26 weeks of initiating anti-PD-1 or anti-PDL-1-based therapy without any evidence of a response. -Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy. -Patients must be able and willing to provide mandatory tumor biopsies prior to and during study treatment., Dose expansion (Part 2B):, -Patients with avanced unresectable or metastatic melanoma who failed after one prior therapy based on anti-PD-1 or anti-PD-L1 or colorectal adenocarcinoma with mesenchymal molecular subtype or urothelial cancer and have failed platinum-containing chemotherapy or non-small cell lung cancer (NSCLC) after failure of anti-PD-1 or anti PD-L1, or hepatocellular carcinoma (HCC) after failure of anti-PD-1 or anti PD-L1, with or without bevacizumab. For all indications patients must not have a suitable alternative approved standard therapy available in the opinion of the investigator or must be refused by the patient., Dose expansion parts 2A and 2B:, -At least 1 measurable lesion by RECIST v1.1.
Exclusion criteria
Exclusion criteria: -Age 1. -Concurrent treatment with any other anticancer therapy (including radiotherapy or investigational agents) or participation in another clinical study. -Washout period of less than 3 weeks to prior anticancer therapy. -Significant and uncontrolled concomitant illness, including any psychiatric condition. -Active infections, including unexplained fever (temperature >38.1ºC), or antibiotic therapy within 1 week prior to enrollment. -Any prior organ transplant including allogeneic bone marrow transplant. -History within the last 5 years of an invasive malignancy other than the one treated in this study. -History of known HIV, unresolved viral hepatitis. -Any major surgery within the last 28 days. -Patients with primary central nervous system (CNS) tumors and/or CNS metastases of non-CNS primary tumors that are untreated. -History of severe, acute or chronic heart diseases. -History of severe, acute or chronic renal diseases or inadequate renal function. -History of significant valvular heart disease (including valve replacement), vascular malformation and anurysm -Any of the following within 6 months prior to study enrollment: pulmonary embolism, deep vein thrombosis, active uncontrolled bleeding, infectious or inflammatory bowel disease, diverticulitis, intestinal obstruction or perforation and gastrointestinal hemorrhage. -Inadequate hematological, renal or liver function. -Non-resolution of any prior treatment related toxicity to Grade 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of SAR439459 and/or REGN2810 (occasional use of inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed). -History of pneumonitis or bowel perforation. -Patients with underlying cancer predisposition syndromes. -Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior the first dose of SAR439459 -Receipt of a live vaccine within 30 days of planned start of study medication. -Prothrombin time (PT) or international normalized ratio (INR) > 1.5 × ULN
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Incidence of DLTs at Cycle 1 and 2 (Day 1 to Day 28) in Parts 1A and 1B. - Objective Response Rate (ORR) for Part 2B: Efficacy as documented by ORR will be assessed by evaluation of anti-tumor response information according to RECIST 1.1 (Part 2A and 2B). | — |
Secondary
| Measure | Time frame |
|---|---|
| - Overall safety profile: The overall safety profile of SAR439459 administered in monotherapy (Part 1A and Part 2A) or in combination with cemplimab (Part 1B and Part 2B). - Immunogenicity evaluation: Blood samples will be assessed for human anti-SAR439459 antibodies (all cohorts) and for human anti- cemiplimab antibodies (Parts 1B and 2B). - Progression free survival (PFS): The time from first IMP administration until objective tumor progression or death (Part 2A and Part 2B). - Time to progression (TTP): The time from first IMP administration until objective tumor progression (Part 2A and 2B). - Objective Response Rate (ORR) for Part 2A: Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2A). - Cmax for SAR439459 and for cemiplimab: Maximum plasma concentration observed. - AUC for SAR439459: Area under the serum concentration versus time curve extrapolated to infinity. - AUClast for SAR439459 and for cemiplimab: Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to last post-dose corresponding to the last concentration above the limit of quantification. - AUC0-14d for SAR439459 and for cemiplimab: Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to 14 days post-dose. - t1/2z for SAR439459: Terminal half-life associated with the terminal slope (*z). - CL for SAR439459: Total body clearance of a drug from plasmacalculated using the following equation from AUC: CL= Dose/AUC on cycle 1. - Vss for SAR439459: Estimate of Volume of distribution at the steady state after single IV dose. | — |
Countries
Netherlands
Outcome results
None listed