Clinical trial NCT03367819: Isatuximab in Combination With REGN2810 (Cemiplimab) 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Non-small Cell Lung Cancer
Keywords: Anti-CD38 monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-12-11
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Random assignment used only for allocation to Cohort A-1 or A-2
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

* To characterize the safety and tolerability of isatuximab in combination with REGN2810 in participants with metastatic, castration-resistant prostate cancer (mCRPC) who were naïve to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PD-L1-containing therapy, and to confirm the recommended Phase 2 dose (RP2D).
* To assess the response rate of isatuximab in combination with REGN2810 in participants with either mCRPC who were anti-PD-1/PD-L1 therapy naive, or NSCLC who progressed on anti-PD-1/PD-L1 therapy, or of isatuximab as single agent in participants 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 participant was 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.

Eligibility criteria: Inclusion Criteria:

* Participants must had 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.
* Greater than or equal to (\>=) 18 years of age.

Exclusion Criteria:

* Prior exposure to isatuximab or participation in clinical studies with isatuximab.
* For participants 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.
* Had received a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus were 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 was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (21 days)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)
measure: Number of Participants With Laboratory Abnormalities: Hematological Parameters
timeFrame: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)
measure: Number of Participants With Laboratory Abnormalities: Electrolytes
timeFrame: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)
measure: Number of Participants With Laboratory Abnormalities: Renal Parameters
timeFrame: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)
measure: Number of Participants With Laboratory Abnormalities: Liver Function Parameters
timeFrame: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)
measure: Overall Response Rate (ORR): Percentage of Participants With Overall Response
timeFrame: From the date of randomization to the date of first documentation of progression or death due to any cause, whichever occurred first (maximum duration: up to 2 years)
Secondary outcomes:
measure: Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab, Post Treatment
timeFrame: From Baseline up to 2 years
measure: Number of Participants With Anti-drug Antibodies (ADA) Response Against REGN2810, Post Treatment
timeFrame: From Baseline up to 2 years
measure: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) After the First Infusion of Isatuximab
timeFrame: At start of infusion (SOI), before actual end of infusion (EOI), EOI+4 hours, 72 hours and 168 hours post-dose on Day 1 of Cycle 1
measure: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) After the First Infusion of REGN2810
timeFrame: At SOI, before actual EOI, EOI+4 hours, 72 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
measure: Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 168 Hours (AUC0-168 hr) After the First Administration of Isatuximab
timeFrame: At SOI, before actual EOI, EOI+4 hours, 72 hours and 168 hours post-dose on Day 1 of Cycle 1
measure: Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504 hr) After the First Administration of REGN2810
timeFrame: At SOI, before actual EOI, EOI+4 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose on Day 1 of Cycle 1
measure: Best Percent-change From Baseline in Tumor Burden
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: From the date of first response until disease progression or death, whichever occurred first (maximum duration: up to 2 years)
measure: Progression-free Survival (PFS)
timeFrame: From the date of the first study treatment administration to the date of first documented disease progression or death of any cause, whichever occurred first (maximum duration: up to 2 years)
measure: Percentage of Participants With Disease Control (DC) >=6 Months
timeFrame: From the date of first response to the date of first documented disease progression or death (due to any cause) (maximum duration: up to 2 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 8400003
state: Alabama
city: Atlanta
country: United States
facility: Investigational Site Number 8400007
state: Georgia
city: Hackensack
country: United States
facility: Investigational Site Number 8400002
state: New Jersey
city: Nashville
country: United States
facility: Investigational Site Number 8400005
state: Tennessee
city: Houston
country: United States
facility: Investigational Site Number 8400004
state: Texas
city: Bordeaux Cedex
country: France
facility: Investigational Site Number 2500002
city: Villejuif
country: France
facility: Investigational Site Number 2500001
city: Rozzano
country: Italy
facility: Investigational Site Number 3800003
state: Milano
city: Orbassano
country: Italy
facility: Investigational Site Number 3800001
state: Torino
city: Napoli
country: Italy
facility: Investigational Site Number 3800006
city: Padova
country: Italy
facility: Investigational Site Number 3800004
city: Verona
country: Italy
facility: Investigational Site Number 3800005
city: Tainan
country: Taiwan
facility: Investigational Site Number 1580002
city: Taipei 100
country: Taiwan
facility: Investigational Site Number 1580001
city: Sutton
country: United Kingdom
facility: Investigational Site Number 8260001
state: Surrey
city: Newcastle upon Tyne
country: United Kingdom
facility: Investigational Site Number 8260002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Zucali PA, Lin CC, Carthon BC, Bauer TM, Tucci M, Italiano A, Iacovelli R, Su WC, Massard C, Saleh M, Daniele G, Greystoke A, Gutierrez M, Pant S, Shen YC, Perrino M, Meng R, Abbadessa G, Lee H, Dong Y, Chiron M, Wang R, Loumagne L, Lepine L, de Bono J. Targeting CD38 and PD-1 with isatuximab plus cemiplimab in patients with advanced solid malignancies: results from a phase I/II open-label, multicenter study. J Immunother Cancer. 2022 Jan;10(1):e003697. doi: 10.1136/jitc-2021-003697.