Clinical trial NCT04045795: Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
Official title: A Multi-center, Open-label, Phase 1b Study to Assess the Pharmacokinetics, Safety, and Efficacy of Subcutaneous and Intravenous Isatuximab (SAR650984) in Combination With Pomalidomide and Dexamethasone, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Anti-CD38 monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-08-06
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

* To evaluate the safety and tolerability of isatuximab administered subcutaneously (SC) versus intravenously (IV)
* To assess the safety and tolerability (including local injection site tolerability) of isatuximab using the (investigational) isatuximab injector device
* To evaluate the pharmacokinetics (PK) of SC and IV isatuximab

Secondary Objectives:

* To estimate absolute bioavailability of SC and IV isatuximab
* To measure receptor occupancy (RO) after isatuximab SC versus IV administration
* To assess efficacy of isatuximab after SC and IV administration
* To assess patient expectations prior to and patient experience and satisfaction after SC administration
* To evaluate potential immunogenicity of SC or IV isatuximab

Detailed description: Total study duration is variable depending on treatment and follow-up periods, including 21 days of screening, and treatment period until disease progression, unacceptable adverse reaction or other reason for discontinuation. End of treatment will be 30 days after last administration of investigational medicinal product, or before further anti-myeloma therapy, whichever comes first; approximately 14 months after first study treatment administration.

Eligibility criteria: Inclusion criteria:

* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
* Participant must be above 18 years of age or country's legal age of majority if the legal age is \>18 years old, at the time of signing the informed consent.
* Participant has been previously diagnosed with multiple myeloma (MM) based on standard criteria and currently requires treatment because MM has relapsed following a response, according to International Myeloma Working Group (IMWG) criteria.
* Participant has received at least two previous therapies including lenalidomide and a proteasome inhibitor and has demonstrated disease progression on last therapy or after completion of the last therapy.
* Participants with measurable disease defined as at least one of the following:
* Serum M protein ≥ 0.5 g/dL (≥5 g/L).
* Urine M protein ≥ 200 mg/24 hours.
* Serum free light chain (FLC) assay: Involved FLC assay ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65).
* Male or female: Contraceptive use by men or women

Exclusion criteria:

* Malignancy within 3 years prior to enrollment.
* Eastern Cooperative Oncology Group (ECOG) performance status score \>2.
* Inadequate hematological, liver or renal function.
* Serum calcium (corrected for albumin) level above the upper limit of normal (ULN) range.
* Patients with prior anti-CD38 treatment are excluded if:

  * Refractory to anti-CD38 treatment defined as progression on or within 60 days of the last dose of the anti-CD38 or,
  * Intolerant to the anti-CD38 previously received or,
  * Progression after initial response on anti-CD38 therapy with a washout period inferior to 9 months before the first dose of isatuximab SC or IV.
* Participant did not achieve a minimal response or better to at least one of the previous lines of treatment (ie, primary refractory disease is not eligible).
* Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
* Prior anti-cancer therapy within 14 days.
* Any \>Grade 1 adverse reaction unresolved from previous treatments according to the NCI-CTCAE v5.0. The presence of alopecia or peripheral neuropathy ≤ Grade 2 without pain is allowed.
* Previous allogeneic stem cell transplantation with active Graft Versus Host Disease or being under immunosuppressive therapy in the last 2 months previously to the inclusion in the trial.
* Daily requirement for corticosteroids.
* Known to be HIV+ or to have hepatitis A or uncontrolled or active hepatitis B virus (HBV) infection (patients with positive HBsAg \[HBsAg\] and/or HBV DNA) or active HCV (HCV) infection (positive HCV RNA and negative anti-HCV).
* Active tuberculosis and severe infections requiring treatment with antibiotic parenteral administration.
* Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.
* History of erythema multiforme or severe hypersensitivity to prior immunomodulatory drugs (IMiDs).
* Hypersensitivity or history of intolerance to immunomodulatory drugs (IMiDs), dexamethasone, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and histamine H2 blockers or would prohibit further treatment with these agents.
* Inability to tolerate thromboprophylaxis.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Assessment of adverse events (AEs)
timeFrame: Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration)
measure: Pharmacokinetic (PK) assessment: Ceoi
timeFrame: Baseline to end of treatment (EOT) after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
measure: PK assessment: Cmax
timeFrame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
measure: PK assessment: tmax
timeFrame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
measure: PK assessment: Clast
timeFrame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
measure: PK assessment: tlast
timeFrame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
measure: PK assessment: Ctrough
timeFrame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
measure: PK assessment: AUClast
timeFrame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
measure: PK assessment: AUC0 T
timeFrame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Secondary outcomes:
measure: Estimation of absolute bioavailability of isatuximab
timeFrame: Day 8
measure: Overall response rate (ORR)
timeFrame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
measure: Duration of response (DOR)
timeFrame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
measure: Time to response (TTR)
timeFrame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
measure: Time to progression (TTP)
timeFrame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
measure: Overall survival (OS)
timeFrame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
measure: Clinical benefit rate (CBR)
timeFrame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
measure: Progression free survival (PFS)
timeFrame: From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
measure: Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires
timeFrame: Cycles 1 and 2 (28 days per Cycle), and 30 days after last isatuximab administration (up to approximately 14 months after first study treatment administration)
measure: Immunogenicity: Anti drug antibody levels
timeFrame: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
measure: Biomarker: Change in CD38 receptor occupancy
timeFrame: At screening and at Day 1 of Cycle 2 (28 days per Cycle) (predose); to be stopped once the isatuximab SC dose has been selected.
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: ~Banner MD Anderson Cancer Center Site Number : 8400005
state: Arizona
city: Duarte
country: United States
facility: City of Hope Site Number : 8400002
state: California
city: Canton
country: United States
facility: Gabrail Cancer Center Site Number : 8400001
state: Ohio
city: Blacktown
country: Australia
facility: Investigational Site Number : 0360002
state: New South Wales
city: Wollongong
country: Australia
facility: Investigational Site Number : 0360001
state: New South Wales
city: Fitzroy
country: Australia
facility: Investigational Site Number : 0360004
state: Victoria
city: Richmond
country: Australia
facility: Investigational Site Number : 0360003
state: Victoria
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Nantes
country: France
facility: Investigational Site Number : 2500001
city: TOULOUSE Cedex 9
country: France
facility: Investigational Site Number : 2500002
city: Okayama-shi
country: Japan
facility: Investigational Site Number : 3920002
state: Okayama
city: Shibuya-ku
country: Japan
facility: Investigational Site Number : 3920001
state: Tokyo
city: Santander
country: Spain
facility: Investigational Site Number : 7240002
state: Cantabria
city: Badalona
country: Spain
facility: Investigational Site Number : 7240001
state: Catalunya [Cataluña]
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: