Clinical trial NCT03194867: Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients
Official title: A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics and Efficacy of Isatuximab in Combination With Cemiplimab in Patients With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Plasma Cell Myeloma
Keywords: Anti-CD38 monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-06-21
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

* To evaluate the safety and tolerability of the combination of isatuximab (also known as SAR650984) and cemiplimab (also known as REGN2810) in patients with relapse/refractory multiple myeloma.
* To compare the overall response of the combination of isatuximab and cemiplimab versus isatuximab alone in patients with RRMM based on International Myeloma Working Group (IMWG) criteria.

Secondary Objectives:

* To evaluate the efficacy as assessed by clinical benefit rate (CBR), duration of response (DOR), time to response (TTR), progression free survival (PFS), and overall survival (OS).
* To assess the pharmacokinetics (PK) of isatuximab and cemiplimab when given in combination.
* To assess the immunogenicity of isatuximab and cemiplimab when given in combination.

Detailed description: The duration of the study for a patient will include a period for screening of up to 21 days and 3-month post treatment follow up. The cycle duration is 28 days. Patients will continue treatment until disease progression, unacceptable adverse events, consent withdrawal, or any other reason.

Eligibility criteria: Inclusion criteria:

* Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, as defined below:

  * Serum M-protein ≥1 g/dL (≥0.5 g/dL in case of immunoglobulin A \[IgA\] disease), AND/OR
  * Urine M-protein ≥200 mg/24 hours, OR
  * In the absence of measurable M-protein, serum immunoglobulin free light chain ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio (\<0.26 or \>1.65).
* Patients must have received prior treatment with an immunomodulatory drug (IMiD) (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (PI) (for ≥2 cycles or ≥2 months of treatment).
* Patients must have received at least 3 prior lines of therapy (Note: Induction therapy and stem cell transplant ± maintenance will be considered as one line).
* Patient must have achieved MR or better with any anti-myeloma therapy (ie, primary refractory disease is not eligible).

Exclusion criteria:

* Prior exposure to isatuximab or participated clinical studies with isatuximab.
* Prior exposure to any agent (approved or investigational) that blocks the programmed cell death-1 (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 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
* Has allogenic haemopoietic stem cell (HSC) transplant.
* Prior treatment with idelalisib (a PI3K inhibitor).
* Eastern Cooperative Oncology Group (ECOG) 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.

Primary outcomes:
measure: Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1 Day 1 to Day 28
measure: Phase 1 and Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: TEAEs were collected from the first dose up to 30 days after the last dose of study treatment, approximately 50 months
measure: Phase 2: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
Secondary outcomes:
measure: Phase 2: Percentage of Participants With Clinical Benefit Rate (CBR)
timeFrame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
measure: Phase 2: Duration of Follow-up
timeFrame: From the date of randomization up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
measure: Phase 2: Duration of Response (DOR)
timeFrame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
measure: Phase 2: Time to Response (TTR)
timeFrame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
measure: Phase 2: Overall Survival (OS)
timeFrame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 17 months
measure: Phase 1 and 2: Plasma Concentration Observed at the End of IV Infusion (Ceoi) of Isatuximab Alone and in Combination With Cemiplimab
timeFrame: At end of infusion (EOI) on Cycle 1 Day 1
measure: Phase 1 and 2: Maximum Observed Concentration (Cmax) of Isatuximab Alone and in Combination With Cemiplimab
timeFrame: At start of infusion (SOI), EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
measure: Phase 1 and 2: Time to Reach Cmax (Tmax) of Isatuximab Alone and in Combination With Cemiplimab
timeFrame: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
measure: Phase 1 and 2: Last Concentration Observed Above the Lower Limit of Quantitation (Clast) of Isatuximab Alone and in Combination With Cemiplimab
timeFrame: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
measure: Phase 1 and 2: Time of Clast (Tlast) of Isatuximab Alone and in Combination With Cemiplimab
timeFrame: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
measure: Phase 1 and 2: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUClast) of Isatuximab Alone and in Combination With Cemiplimab
timeFrame: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
measure: Phase 1 and 2: AUC From Time 0 to Week 1 (AUC1week) of Isatuximab Alone and in Combination With Cemiplimab
timeFrame: At SOI, EOI, EOI+4 hours, 72 hours and 168 hours on Day 1 of Cycle 1
measure: Phase 1 and 2: Number of Participants With Anti-Drug Antibodies (ADA) to Isatuximab
timeFrame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 20 months
measure: Phase 1 and 2: Number of Participants With ADA to Cemiplimab
timeFrame: From Cycle 1 Day 1 up to primary analysis completion date of 9 Oct 2019 i.e., up to approximately 20 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado-Site Number:8400001
state: Colorado
city: Kansas City
country: United States
facility: University of Kansas Medical Center-Site Number:8400003
state: Kansas
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center-Site Number:8400002
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center-Site Number:8400004
state: Pennsylvania
city: Wollongong
country: Australia
facility: Investigational Site Number :0360003
state: New South Wales
city: Richmond
country: Australia
facility: Investigational Site Number :0360002
state: Victoria
city: West Perth
country: Australia
facility: Investigational Site Number :0360001
state: Western Australia
city: Goiania
country: Brazil
facility: Investigational Site Number :0760003
state: Goiás
city: Porto Alegre
country: Brazil
facility: Investigational Site Number :0760001
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Investigational Site Number :0760004
state: São Paulo
city: Montreal
country: Canada
facility: Investigational Site Number :1240001
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number :1240005
state: Quebec
city: Sherbrooke
country: Canada
facility: Investigational Site Number :1240003
state: Quebec
city: Brno
country: Czechia
facility: Investigational Site Number :2030002
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number :2030003
city: Praha 2
country: Czechia
facility: Investigational Site Number :2030001
city: Lille
country: France
facility: Investigational Site Number :2500004
city: Nantes
country: France
facility: Investigational Site Number :2500002
city: Pierre Benite
country: France
facility: Investigational Site Number :2500003
city: Villejuif
country: France
facility: Investigational Site Number :2500001
city: Athens
country: Greece
facility: Investigational Site Number :3000001
city: Budapest
country: Hungary
facility: Investigational Site Number :3480002
city: Rozzano
country: Italy
facility: Investigational Site Number :3800005
state: Milano
city: Brescia
country: Italy
facility: Investigational Site Number :3800003
city: Torino
country: Italy
facility: Investigational Site Number :3800001
city: Barcelona
country: Spain
facility: Investigational Site Number :7240003
state: Barcelona [Barcelona]
city: Badalona
country: Spain
facility: Investigational Site Number :7240004
state: Catalunya [Cataluña]
city: Barcelona
country: Spain
facility: Investigational Site Number :7240002
state: Catalunya [Cataluña]
city: Valencia
country: Spain
facility: Investigational Site Number :7240005
state: Valenciana, Comunidad
city: Madrid
country: Spain
facility: Investigational Site Number :7240006
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: