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Prostate CancerPhase 1/2NCT03367819

Isatuximab in Combination With REGN2810 (Cemiplimab) in Patients With Advanced Malignancies

A Phase 1/2 study testing Isatuximab SAR650984 and Cemiplimab REGN2810 in people with Prostate Cancer and Non-small Cell Lung Cancer, run by Sanofi at 16 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Prostate Cancer, Non-small Cell Lung Cancer
What is being tested?
Isatuximab SAR650984 and Cemiplimab REGN2810
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
16 sitesin 5 countries
Study dates
4 Jan 2018to 10 Mar 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

16 sites in 5 countries.

16 sites in 5 countries

United States5 sites

  • Investigational Site Number 8400007

    Atlanta, Georgia, 30322

  • Investigational Site Number 8400003

    Birmingham, Alabama, 35249

  • Investigational Site Number 8400002

    Hackensack, New Jersey, 07601

  • Investigational Site Number 8400004

    Houston, Texas, 77030

  • Investigational Site Number 8400005

    Nashville, Tennessee, 37203

Other trials in United States

Italy5 sites

  • Investigational Site Number 3800006

    Naples, 80131

  • Investigational Site Number 3800001

    Orbassano, Torino, 10043

  • Investigational Site Number 3800004

    Padova, 35128

  • Investigational Site Number 3800003

    Rozzano, Milano, 20089

  • Investigational Site Number 3800005

    Verona, 37134

Other trials in Italy

France2 sites

  • Investigational Site Number 2500002

    Bordeaux, 33076

  • Investigational Site Number 2500001

    Villejuif, 94800

Other trials in France

Taiwan2 sites

  • Investigational Site Number 1580002

    Tainan, 704

  • Investigational Site Number 1580001

    Taipei

Other trials in Taiwan

United Kingdom2 sites

  • Investigational Site Number 8260002

    Newcastle upon Tyne, NE7 7DN

  • Investigational Site Number 8260001

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

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

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.
Read more

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.
Read the 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.

Being tested
Isatuximab SAR650984, Cemiplimab REGN2810
Keywords
Anti-CD38 monoclonal antibody
Medical subject headings
Prostatic Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Isatuximab SAR650984Drug

    Also called Sarclisa

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous

  • Cemiplimab REGN2810Drug

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous

Study groups in NCT03367819
Study groupRoleWhat they receive
Phase 1: mCRPC/NSCLCExperimentalIsatuximab dose 1 and REGN2810 predefined dose
Receives: Drug: Isatuximab SAR650984; Drug: Cemiplimab REGN2810
Cohort A-1: mCRPC, isatuximab and REGN2810 combinationExperimentalParticipants with mCRPC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose
Receives: Drug: Isatuximab SAR650984; Drug: Cemiplimab REGN2810
Cohort A-2: mCRPC, isatuximab monotherapyExperimentalParticipants with mCRPC will be given isatuximab dose 2
Receives: Drug: Isatuximab SAR650984
Phase 2 Cohort B: NSCLCExperimentalParticipants with NSCLC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose
Receives: Drug: Isatuximab SAR650984; Drug: Cemiplimab REGN2810
Possibly Phase 2 Cohort C: mCRPCExperimentalIsatuximab dose 3 will be given in combination with REGN2810 predefined dose or isatuximab dose 3 will be given as monotherapy in participants with mCRPC
Receives: Drug: Isatuximab SAR650984; Drug: Cemiplimab REGN2810
Possibly Phase 2 Cohort D: NSCLCExperimentalIsatuximab dose 3 will be given in combination with REGN2810 predefined dose
Receives: Drug: Isatuximab SAR650984; Drug: Cemiplimab REGN2810

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose Limiting Toxicities (DLTs)

    DLTs: adverse events occurring during 1st treatment cycle, unless due to disease progression/to cause obviously unrelated to investigational medicinal product (IMP) which included:hematological abnormalities: Grade(G) 4 neutropenia(N) for 7/more consecutive days, G3 to G4 N with fever (temperature greater than or equal to [>=] 38.5 degree Celsius on more than 1 occasion) or microbiologically/radiographically documented infection, G3 to G4 thrombocytopenia with clinically significant bleeding. Non-hematological abnormalities: G4 non-hematologic AE, G>=2 uveitis, G3 non-hematological AE lasting greater than (>)3 days (except G3 fatigue, allergic reaction/hypersensitivity attributed to isatuximab or REGN2810 and G3 or G4 clinically non-significant laboratory abnormality), delay in initiation of Cycle 2 >14 days due to treatment related laboratory abnormalities/AE. Any other toxicity that Investigator and Sponsor deemed to be dose-limiting, regardless of grade, was also considered as DLT.

    Measured: Cycle 1 (21 days)

  2. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

    An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (defined as the time from the first dose of study treatment up to 30 days after the last dose of study treatment). TEAEs included both SAEs and non-SAEs.

    Measured: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

  3. Number of Participants With Laboratory Abnormalities: Hematological Parameters

    Hematological parameters assessed were anemia, white blood cell (WBC) decreased, platelet count decreased, lymphocyte count decreased and neutrophil count decreased. Abnormality criteria was based on National Cancer Institute Common Terminology Criteria for Adverse Event version 4.03 (NCI-CTCAE v 4.03), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Only those categories in which at least 1 participant had data were reported.

    Measured: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

  4. Number of Participants With Laboratory Abnormalities: Electrolytes

    Abnormal electrolytes parameters assessed were hyponatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypoalbuminemia and hyperglycemia. Abnormality criteria was based on NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Only those categories in which at least 1 participant had data were reported.

    Measured: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

  5. Number of Participants With Laboratory Abnormalities: Renal Parameters

    Abnormal renal parameters assessed were creatinine clearance (CrCl), creatinine increased and hyperuricemia. Creatinine clearance was assessed in categories: >=60 - less than (<) 90 milliliters per minute per 1.73 square meter (mL/min/1.73m^2), >=30 - <60 mL/min/1.73m^2, >=15 - <30 mL/min/1.73m^2 and <15 mL/min/1.73m^2. Creatinine increased and hyperuricemia abnormality criteria was based on NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. For all these 3 parameters, only those categories in which at least 1 participant had data were reported.

    Measured: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

  6. Number of Participants With Laboratory Abnormalities: Liver Function Parameters

    Abnormal liver function parameters assessed were aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, blood bilirubin (BB) increased. Abnormality criteria was based on NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Only those categories in which at least 1 participant had data were reported.

    Measured: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

  7. Overall Response Rate (ORR): Percentage of Participants With Overall Response

    For participants with mCRPC, response was defined as achieving complete response (CR) or partial response (PR) as best overall response (BOR) for soft tissue assessed and confirmed by the Investigators and/or a prostate-specific antigen (PSA) decline of >=50 percent (%) from Baseline that was subsequently confirmed per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. For participants with NSCLC, ORR was defined as the percentage of participants with CR or PR as BOR according to RECIST 1.1. criteria. Per RECIST 1.1. criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <10 millimeters (mm) and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.

    Measured: 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 (10)

  1. Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab, Post Treatment

    ADA response were categorized as treatment boosted ADA and treatment-induced ADA. Treatment boosted ADA was defined as pre-existing ADAs with a significant increase in the ADA titer during the study compared to the Baseline titer. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without pre-existing ADA (including participants without pretreatment samples).

    Measured: From Baseline up to 2 years

  2. Number of Participants With Anti-drug Antibodies (ADA) Response Against REGN2810, Post Treatment

    ADA response were categorized as treatment boosted ADA and treatment-induced ADA. Treatment boosted ADA was defined as pre-existing ADAs with a significant increase in the ADA titer during the study compared to the Baseline titer. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without pre-existing ADA (including participants without pretreatment samples).

    Measured: From Baseline up to 2 years

  3. Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) After the First Infusion of Isatuximab

    Cmax was defined as the maximum observed plasma concentration. Cmax analysis was done separately for isatuximab for participants with mCRPC and NSCLC.

    Measured: 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

  4. Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) After the First Infusion of REGN2810

    Cmax was defined as the maximum observed plasma concentration. Cmax analysis was done separately for REGN2810 for participants with mCRPC and NSCLC.

    Measured: At SOI, before actual EOI, EOI+4 hours, 72 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1

  5. Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 168 Hours (AUC0-168 hr) After the First Administration of Isatuximab

    AUC0-168 hr was defined as the area under the plasma concentration-time curve from time zero to 168h and was calculated using the trapezoidal method over the dosing interval (i.e., 7 days) for isatuximab alone.

    Measured: At SOI, before actual EOI, EOI+4 hours, 72 hours and 168 hours post-dose on Day 1 of Cycle 1

  6. Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504 hr) After the First Administration of REGN2810

    AUC0-504 hr was defined as the area under the plasma concentration-time curve from time zero to 504h and was calculated using the trapezoidal method over the dosing interval (i.e., 21 days) for REGN2810 alone.

    Measured: 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

  7. Best Percent-change From Baseline in Tumor Burden

    Tumor burden change was defined as 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.

    Measured: Up to 2 years

  8. Duration of Response (DOR)

    DOR: defined as time (in months) from date of first response (PR or CR in radiographic objective response, or PSA decline >=50% for participants with mCRPC) that was subsequently confirmed to the date of first disease progression (PD) or death, whichever occurred first. PD included radiographic disease progression or unequivocal clinical progression. RECIST 1.1 criteria was used to assess radiographic PD in participants with NSCLC and PCWG3 criteria for participants with mCRPC. Per RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target/non-target) must had reduction in short axis to <10 mm and PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (Baseline sum if that was smallest), sum with an absolute increase of at least 5 mm and appearance of 1 or more new lesions.

    Measured: From the date of first response until disease progression or death, whichever occurred first (maximum duration: up to 2 years)

  9. Progression-free Survival (PFS)

    For mCRPC participants, PFS was defined as the time (in months) from first study treatment administration to the date of first documented disease progression or the date of death from any cause, whichever occurred first. Disease progression included radiographic disease progression (per PCWG3 criteria) or unequivocal clinical progression. For NSCLC participants, PFS was defined as the time from first study treatment administration to the date of first documented radiographic progression (PD) (per RECIST 1.1) or the date of death from any cause, whichever occurred first. Per RECIST 1.1 criteria, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the Baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered as progression. Analysis was performed using Kaplan-Meier method.

    Measured: 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)

  10. Percentage of Participants With Disease Control (DC) >=6 Months

    Disease control: defined as percentage of participants with confirmed CR/PR/stable disease (SD), as assessed by Investigator PCWG3 modified RECIST 1.1 criteria relative to total number of participants in analysis population. Per PCWG3 modified RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target/non-target) must had reduction in short axis to <10 mm, PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference Baseline sum diameters and SD: neither sufficient shrinkage from the Baseline to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters while on study. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum with an absolute increase of diameter of at least 5 mm and appearance of 1 or more new lesions.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2017
  2. Study start4 Jan 2018
  3. Primary completion10 Mar 2021
  4. Study completion10 Mar 2021

Why it stopped: The study was stopped after interim analysis indicated that overall result was not sufficient to satisfy per-protocol criteria to move forward in metastatic, castration-resistant prostate cancer (mCRPC) and non-small cell lung cancer (NSCLC) cohorts.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Random assignment used only for allocation to Cohort A-1 or A-2
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03367819
Sponsor's protocol ID
ACT15319
Other IDs
2017-002846-61, U1111-1197-7792, 2017
Status last verified
Apr 2022
First submitted
5 Dec 2017
Last updated
16 May 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • 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.

    PubMed 35058326

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Isatuximab SAR650984 and Cemiplimab REGN2810 in people with Prostate Cancer and Non-small Cell Lung Cancer, run by Sanofi at 16 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Italy, France, Taiwan, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (21 days)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03367819, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2022.

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