Safety, Preliminary Efficacy and PK of Isatuximab (SAR650984) Alone or in Combination With Atezolizumab in Patients With Advanced Malignancies
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03637764 |
|
Recruitment Status :
Completed
First Posted : August 20, 2018
Last Update Posted : June 9, 2022
|
Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
- Study Details
- Tabular View
- Results Submitted
- Disclaimer
- How to Read a Study Record
Brief Summary:
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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neoplasm | Drug: Isatuximab SAR650984 Drug: Atezolizumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 107 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | August 6, 2018 |
| Actual Primary Completion Date : | May 11, 2022 |
| Actual Study Completion Date : | May 11, 2022 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Phase1
Isatuximab and atezolizumab combination in patients 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): Isatuximab dose 1 depending on DLT observed and atezolizumab predefined dose Q3W |
Drug: Isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Sarclisa Drug: Atezolizumab Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Tecentriq® |
|
Experimental: Phase2-Cohort A: HCC
Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
|
Drug: Isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Sarclisa Drug: Atezolizumab Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Tecentriq® |
|
Experimental: Phase2-Cohort B: SCCHN
Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
|
Drug: Isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Sarclisa Drug: Atezolizumab Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Tecentriq® |
|
Experimental: Phase2-Cohort C: EOC
Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
|
Drug: Isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Sarclisa Drug: Atezolizumab Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Tecentriq® |
|
Experimental: Phase2-Cohort D-1:GBM
Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
|
Drug: Isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Sarclisa Drug: Atezolizumab Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Tecentriq® |
|
Experimental: Phase2-Cohort D-2: GBM, isatuximab monotherapy
Isatuximab dose 2
|
Drug: Isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Sarclisa |
|
Experimental: Phase2-Cohort E
Isatuximab and atezolizumab combination: Isatuximab dose 3 and atezolizumab predefined dose Q3W in participants with one tumor type (HCC, SCCHN, EOC, or GBM), or isatuximab monotherapy (GBM only) dose 3
|
Drug: Isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Sarclisa Drug: Atezolizumab Pharmaceutical form: solution for infusion Route of administration: intravenous Other Name: Tecentriq® |
Primary Outcome Measures :
- Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 3 weeks after first study treatment administration ]DLTs as observed during DLT-observation period
- Adverse events (AEs) [ Time Frame: Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration) ]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
- Maximum tolerated dose (MTD) [ Time Frame: Up to 3 weeks after first study treatment administration ]MTD determined during Phase 1
- Recommended Phase 2 dose (RP2D) [ Time Frame: Up to 3 weeks after first study treatment administration ]Dose selected for the Phase 2 portion
- Response Rate [ Time Frame: Up to 6 months after last patient's first treatment in a given cohort ]In patients 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) assessed by using RECIST 1.1
- Progression free survival [ Time Frame: Up to 6 months after last patient's first treatment ]In patients with glioblastoma multiforme (GBM) assessed by using Response Assessment for Neuro-Oncology (RANO) criteria at 6 months
Secondary Outcome Measures :
- Immunogenicity: isatuximab [ Time Frame: Up to 90 days following the last administration of study treatment (Up to approximately 27 months after first study treatment administration) ]Levels of anti-drug antibody against isatuximab
- Immunogenicity: atezolizumab [ Time Frame: Up to 30 days following the last administration of study treatment (Up to approximately 25 months after first study treatment administration) ]Levels of anti-drug antibody against atezolizumab
- Tumor burden change [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]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
- Disease control rate [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
- Duration of response [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]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.
- Progress free survival [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]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
- Response Rate [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]In GBM assessed by RANO criteria
- Pharmacokinetic (PK) parameters: Area under the curve (AUC0-T) [ Time Frame: From pre-isatuximab-dose on Cycle 1 Day 1 to 168 hours after start of isatuximab dose on Cycle 1 Day 1 (duration of assessment: 7 days; overall cycle duration: 21 days) ]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.
- Assessment of PK parameter: Cmax [ Time Frame: From pre-isatuximab-dose on Cycle 1 Day 1 to 168 hours after start of isatuximab dose on Cycle 1 Day 1 (duration of assessment: 7 days; overall cycle duration: 21 days) ]Cmax is maximum drug concentration observed
- Assessment of PK parameter: tmax [ Time Frame: From pre-isatuximab-dose on Cycle 1 Day 1 to 168 hours after start of isatuximab dose on Cycle 1 Day 1 (duration of assessment: 7 days; overall cycle duration: 21 days) ]Time to reach Cmax
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03637764
Locations
Show 27 study locations
Sponsors and Collaborators
Sanofi
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT03637764 |
| Other Study ID Numbers: |
ACT15377 2018-000390-67 ( EudraCT Number ) U1111-1202-0839 ( Other Identifier: UTN ) |
| First Posted: | August 20, 2018 Key Record Dates |
| Last Update Posted: | June 9, 2022 |
| Last Verified: | June 8, 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Sanofi:
|
Anti-CD38 monoclonal antibody |
Additional relevant MeSH terms:
|
Neoplasms Atezolizumab Immune Checkpoint Inhibitors |
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Antineoplastic Agents |