Neoplasm MedDRA version: 20.0 Level: PT Classification code 10028980 Term: Neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients must have a known diagnosis of either unresectable hepatocellular carcinoma (HCC), platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN), platinum-resistant/refractory epithelial ovarian cancer (EOC) with evidence of measurable disease or recurrent glioblastoma multiforme (GBM). - =18 years of age. -For patients with HCC: Documentation of progressive disease (PD) during or after treatment with either sorafenib or lenvatinib, or intolerance to the therapy. -For patients with SCCHN: Received and failed up to 2 lines of prior systemic anti-cancer therapy with documentation of tumor recurrence or PD within 6 months of last platinum-based therapy in primary, recurrent, or metastatic setting. -For patients with EOC: Received up to 3 lines of prior platinum- containing therapy when the disease was platinum-sensitive, and the patients should not have received any systemic therapy for platinum-resistant/refractory disease. specific to France only: Documentation of PD on or after 1 line of anti-cancer therapy for platinum resistant/refractory disease (unless patients are ineligible or intolerant to standard of care for platinum-resistant/refractory disease). -For patients with GBM: Documentation of PD or first recurrence during or after temozolomide maintenance therapy for newly diagnosed GBM treated with 1st line radiotherapy plus concurrent temozolomide. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 289 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 96
Exclusion criteria
Exclusion criteria: - Prior exposure to agent that blocks CD38 or participation in clinical studies with isatuximab - For patients with HCC, SCCHN, EOC or GBM prior exposure to any agent (approved or investigational) that blocks the PD-1/PD-L1 pathway. - Evidence of other immune related disease /conditions. - History of non-infectious pneumonitis requiring steroids or current pneumonitis; history of the thoracic radiation. - Has received a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. - Prior solid organ or bone marrow transplantation. - Eastern Cooperative Oncology Group performance status (PS) =2 for patients with HCC, SCCHN or EOC or Karnofsky performance score = 70 for patients with GBM - Poor bone marrow reserve. - Poor organ function.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -Phase1: To characterize the safety and tolerability of isatuximab in combination with atezolizumab in participants with unresectable hepatocellular carcinoma (HCC), platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN), platinumresistant/ refractory epithelial ovarian cancer (EOC), or recurrent glioblastoma multiforme (GBM), and to determine the recommended Phase 2 dose (RP2D). - Phase2: To assess response rate (RR) of isatuximab in combination with atezolizumab in participants with HCC or SCCHN or EOC. - Phase2: To assess the progression free survival rate at 6 months (PFS-6) of isatuximab in combination with atezolizumab, or as a single agent in participants with GBM.;Secondary Objective: -To evaluate the safety profile of isatuximab monotherapy (GBM only), or in combination with atezolizumab in Phase 2. -To evaluate the immunogenicity of isatuximab and atezolizumab -To characterize the pharmacokinetic (PK) profile of isatuximab single agent (GBM only) and atezolizumab in combination with isatuximab. -To assess the overall efficacy of isatuximab in combination with atezolizumab, or single agent (GBM only).;Primary end point(s): 1) Dose Limiting Toxicities (DLTs): DLTs as observed during DLTobservation period 2) Adverse events (AEs): Number of patients with AEs based on standard and systematic assessment including changes in laboratory tests and vital signs, according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling 3) Maximum tolerated dose (MTD): MTD determined during Phase 1 4) Recommended Phase 2 dose (RP2D): Dose selected for the Phase 2 portion 5) Response Rate: In patients with unresectable hepatocellular carcinoma (HCC), platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN), platinumresistant/refractory epithelial ovarian cancer assessed by using RECIST 1.1 6) Progression free survival: In patients with glioblastom | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Immunogenicity: isatuximab: Levels of anti-drug antibody against isatuximab 2) Immunogenicity: atezolizumab: Levels of anti-drug antibody against atezolizumab 3) Tumor burden change: The best percent-change from baseline in a sum of the diameters (longest for non-nodal lesion, short axis for nodal lesions) for all target lesions in participants with HCC, SCCHN and EOC, and in a sum of products of diameters for all target lesions in participants with GBM. 4) Disease control rate: The sum of complete responses (CR) + partial responses (PR) + stable disease (SD) 5) Duration of response: The time from the date of the first response (PR or CR in radiographic objective response) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first. 6) Progress free survival: The time from the first study treatment administration to the date of first documentation of progressive disease (RECIST 1.1 for participants with HCC, SCCHN, EOC and RANO criteria for participants with GBM) or the date of death from any cause 7) Response Rate: In GBM assessed by RANO criteria 8) Pharmacokinetic (PK) parameters: Area under the curve (AUC0-T): AUC0-T is the area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (T; i.e., 7 days for isatuximab) after the first infusion 9) Assessment of PK parameter: Cmax: Cmax is maximum drug concentration observed 10) Assessment of PK parameter: tmax : Time to reach Cmax;Timepoint(s) of evaluation of this end point: 1) Up to 90 days following the last administration of study treatment (Up to approximately 27 months after first study treatment administration) 2) Up to 30 days following the last administration of study treatment (Up to approximately 25 months after first study treatment administration) 3) to 7) Up to 12 months after last patient's first treatment in a given cohort 8) to 10) From pre-isatuxima | — |
Countries
Belgium, Canada, Czech Republic, France, Greece, Italy, Netherlands, Spain, Taiwan, United States
Contacts
Public Contactwww.sanofi.cz
sanofi-aventis, s.r.o.
Outcome results
None listed