Isatuximab in Combination With REGN2810 in Patients With Advanced Malignancies

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer Prostate Cancer	Drug: Isatuximab SAR650984 Other Names Drug: REGN2810 Other Names	Phase 1/Phase 2

Tracking Information

First Submitted Date	December 05, 2017
Last Update Posted Date	February 14, 2018
Actual Start Date	January 04, 2018
Anticipated Completion Date	July 30, 2021
Actual Primary Completion Date	July 30, 2021
Results First Submitted Date	N/A
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• Response Rate [Time Frame: Up to 6 months from last patient in]

  In non-small cell lung cancer (NSCLC): assessed and objective responses by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; In metastatic castration-resistant prostate cancer (mCRPC): response will be defined per Prostate Cancer Working Group 3 (PCWG3) criteria

• AEs [Time Frame: Up to 30 days after last study treatment administration (Up to approximately 25 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

• Dose Limiting Toxicities (DLTs) [Time Frame: Up to 3 weeks after first study treatment administration]

  DLTs are following adverse events (AEs) in Cycle 1 unless due to disease progression or an obviously unrelated cause: Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention; G 4 non-hematological AE; G ≥2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AEs

Original Primary Outcome Measures

Current Secondary Outcome Measures

• Immunogenicity: isatuximab [Time Frame: Up to 90 days following the last administration of study treatment or until the sample is negative (Up to approximately 27 months after first study treatment administration)]

  Levels of anti-drug antibody against isatuximab

• Pharmacokinetic (PK) parameters: area under the curve (AUC) [Time Frame: Up to 3 weeks after first study treatment administration]

  AUC is area under the drug concentration versus time curve

• Tumor burden change [Time Frame: Up to 6 months from last patient in]

  The best percent-change from baseline in a sum of the diameters for all target lesions

• Duration of response [Time Frame: Up to 6 months from last patient in]

  Defined as the time from the date of the first 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 6 months from last patient in]

  Defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause

• Assessment of PK parameter: Cmax [Time Frame: Up to 3 weeks after first study treatment administration]

  Cmax is maximum drug concentration observed

• Immunogenicity: REGN2810 [Time Frame: Up to 90 days following the last administration of study treatment or until the sample is negative (Up to approximately 27 months after first study treatment administration)]

  Levels of anti-drug antibody against REGN2810

Original Secondary Outcome Measures

Study Design

Brief Title	Isatuximab in Combination With REGN2810 in Patients With Advanced Malignancies
Official Title	A Phase 1/2 Open-label, Multi-center, Safety, Preliminary Efficacy and Pharmacokinetic (PK) Study of Isatuximab (SAR650984) in Combination With REGN2810, or Isatuximab Alone, in Patients With Advanced Malignancies
Brief Summary	Primary Objectives: - To characterize the safety and tolerability of isatuximab in combination with REGN2810 in patients with metastatic, castration-resistant prostate cancer (mCRPC) who are naïve to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PDL-1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PDL-1-containing therapy, and to confirm the recommended Phase 2 dose (RP2D). - To assess the response rate of isatuximab in combination with REGN2810 in patients with either mCRPC who are anti-PD-1/PDL-1 therapy naive, or NSCLC who progressed on anti-PD-1/PDL-1 therapy, or of isatuximab as single agent in patients with mCRPC. Secondary Objectives: - To evaluate the safety of the combination of isatuximab with REGN2810 or isatuximab monotherapy. - To evaluate the immunogenicity of isatuximab and REGN2810. - To characterize the pharmacokinetic (PK) profile of isatuximab single agent or in combination with REGN2810, and to characterize the PK of REGN2810 in combination with isatuximab. - To assess overall efficacy of isatuximab in combination with REGN2810 or as a single agent.
Detailed Description	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.
Study Type	Interventional
Study Phase	Phase 1/Phase 2
Estimated Enrollment	134
Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
Conditions	Non-small Cell Lung Cancer Prostate Cancer
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Drug: Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous Other Names Drug: REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous Other Names
Study Groups/Cohorts	Phase 1: mCRPC/NSCLC Isatuximab dose 1 and REGN2810 predefined dose Cohort A-1: mCRPC, isatuximab and REGN2810 combination Patients with mCRPC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose Cohort A-2: mCRPC, isatuximab monotherapy Patients with mCRPC will be given isatuximab dose 2 Phase 2 Cohort B: NSCLC Patients with NSCLC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose Phase 2 Cohort C: mCRPC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose or isatuximab dose 3 will be given as monotherapy in patients with mCRPC Phase 2 Cohort D: NSCLC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose
Study Arms	Experimental Cohort A-1: mCRPC, isatuximab and REGN2810 combination Patients with mCRPC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Cohort A-1: mCRPC, isatuximab and REGN2810 combination Patients with mCRPC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Cohort A-2: mCRPC, isatuximab monotherapy Patients with mCRPC will be given isatuximab dose 2 Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Phase 1: mCRPC/NSCLC Isatuximab dose 1 and REGN2810 predefined dose Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Phase 1: mCRPC/NSCLC Isatuximab dose 1 and REGN2810 predefined dose Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Phase 2 Cohort B: NSCLC Patients with NSCLC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Phase 2 Cohort B: NSCLC Patients with NSCLC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Phase 2 Cohort C: mCRPC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose or isatuximab dose 3 will be given as monotherapy in patients with mCRPC Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Phase 2 Cohort C: mCRPC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose or isatuximab dose 3 will be given as monotherapy in patients with mCRPC Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Phase 2 Cohort D: NSCLC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous Experimental Phase 2 Cohort D: NSCLC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous

Arm	Intervention/Treatment
Experimental Cohort A-1: mCRPC, isatuximab and REGN2810 combination Patients with mCRPC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose	Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Cohort A-1: mCRPC, isatuximab and REGN2810 combination Patients with mCRPC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose	Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Cohort A-2: mCRPC, isatuximab monotherapy Patients with mCRPC will be given isatuximab dose 2	Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Phase 1: mCRPC/NSCLC Isatuximab dose 1 and REGN2810 predefined dose	Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Phase 1: mCRPC/NSCLC Isatuximab dose 1 and REGN2810 predefined dose	Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Phase 2 Cohort B: NSCLC Patients with NSCLC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose	Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Phase 2 Cohort B: NSCLC Patients with NSCLC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose	Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Phase 2 Cohort C: mCRPC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose or isatuximab dose 3 will be given as monotherapy in patients with mCRPC	Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Phase 2 Cohort C: mCRPC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose or isatuximab dose 3 will be given as monotherapy in patients with mCRPC	Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Phase 2 Cohort D: NSCLC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose	Drug : Isatuximab SAR650984 Pharmaceutical form: solution for infusion Route of administration: intravenous
Experimental Phase 2 Cohort D: NSCLC Isatuximab dose 3 will be given in combination with REGN2810 predefined dose	Drug : REGN2810 Pharmaceutical form: solution for infusion Route of administration: intravenous

Recruitment Information

Recruitment Status:	Recruiting
Enrollment	134
Completion Date	July 30, 2021
Eligibility Criteria:	Inclusion criteria: - Patients must have a known diagnosis of either metastatic castration-resistant prostate cancer (mCRPC) or non-small cell lung cancer (NSCLC) with evidence of measurable disease. - Failure of, inability to, or refusal to receive standard of care. - ≥18 years of age. Exclusion criteria: - Prior exposure to isatuximab or participation in clinical studies with isatuximab. - For patients with mCRPC, 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 hematologic transplant. - Eastern Cooperative Oncology Group performance status (PS) ≥2. - 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.
Gender	All
Age	18 Years to N/A
Accepts Healthy Volunteers	No
Contacts	For site information, send an email with site number to [email protected]
Listed Location Countries	Taiwan

Administrative Information

NCT Number:	NCT03367819
Other Study ID Numbers	ACT15319 2017-002846-61 U1111-1197-7792
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	,
Study Sponsor	Sanofi
Collaborators	Not Available
Investigators	Study Director Clinical Sciences & Operations Sanofi