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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.

Massachusetts

Boston
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

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: CLOSED_TO_ACCRUAL

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
  • Clinicaltrials.gov ID NCT03637764