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Safety, Preliminary Efficacy and PK of Isatuximab (SAR650984) Alone or in Combination With Atezolizumab in Patients With Advanced Malignancies

Trial Status: Active

Primary Objectives: - 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), platinum-resistant / 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 Objectives: - 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).

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.

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.


Beth Israel Deaconess Medical Center
Status: ACTIVE
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE


Fox Chase Cancer Center
Status: ACTIVE


M D Anderson Cancer Center
Status: ACTIVE


Fred Hutch / University of Washington Cancer Consortium

The total study duration per patient is up to 28 months including an up to 28 days screening period, an up to 24 months treatment period, and a 3 months safety follow up period.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Sanofi Aventis

  • Primary ID ACT15377
  • Secondary IDs NCI-2019-01360, 2018-000390-67, U1111-1202-0839
  • ID NCT03637764