A Phase 1/2 open-label, multi-center, safety, preliminary efficacy and pharmacokinetic (PK) study of isatuximab (SAR650984) in combination with atezolizumab or isatuximab alone in patients with advanced malignancies
- Conditions
- Advanced solid tumors10027655
- Registration Number
- NL-OMON46722
- Lead Sponsor
- Sanofi-aventis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 24
- 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 and failed 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.;-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.
- 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase 1:<br /><br>- Dose limiting toxicities (DLTs) (in Cycle 1)<br /><br>- Adverse events (AEs)/serious adverse events (SAEs),<br /><br>- Laboratory abnormalities and the recommended Phase 2 dose (RP2D) defined as<br /><br>the dose selected for the Phase 2 portion.<br /><br><br /><br>Phase 2 :<br /><br>- RR defined as the proportion of patients with complete response and partial<br /><br>response as best overall response (assessed by Investigators using RECIST<br /><br>criteria 1.1 for patients with HCC, SCCHN and EOC;<br /><br>- PFS-6 defined as the PFS rate at 6 months assessed by Investigators using<br /><br>RANO criteria for GBM.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Phase 2:<br /><br>- Adverse events (AE)/serious AEs and laboratory abnormalities;<br /><br>- Incidence rate of anti-drug antibodies development (ADA: anti-isatuximab and<br /><br>anti-atezolizumab antibodies)<br /><br>- PK assessed from concentrations of isatuximab (non-compartmental analysis and<br /><br>population PK approach) and atezolizumab (population PK approach).<br /><br>- Best percent-change from baseline in tumor burden change, disease control<br /><br>rate (DCR) defined as the sum of the complete response, partial response and<br /><br>stable disease rates, duration of response (DoR), progression free survival<br /><br>(PFS) (HCC, SCCHN, EOC per RECIST 1.1 and GBM per RANO criteria), RR (GBM only,<br /><br>per RANO criteria).</p><br>