Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04045795
• Other study ID #: TCD15484
• Secondary ID: U1111-1211-95252
• Status: Completed
• Phase: Phase 1
• Start date: August 6, 2019
• Est. completion date: March 27, 2024

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: March 27, 2024
• Est. primary completion date: March 27, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• isatuximab SAR650984 IV
Pharmaceutical form: solution Route of administration: intravenous
• pomalidomide
Pharmaceutical form: tablet Route of administration: oral
• dexamethasone
Pharmaceutical form: tablet Route of administration: oral
• isatuximab SAR650984 SC
Pharmaceutical form: solution Route of administration: subcutaneous

Device:
• Investigational injector device
Subcutaneous administration

Locations

Country	Name	City	State
Australia	Investigational Site Number : 0360002	Blacktown	New South Wales
Australia	Investigational Site Number : 0360004	Fitzroy	Victoria
Australia	Investigational Site Number : 0360003	Richmond	Victoria
Australia	Investigational Site Number : 0360001	Wollongong	New South Wales
Belgium	Investigational Site Number : 0560001	Leuven
France	Investigational Site Number : 2500001	Nantes
France	Investigational Site Number : 2500002	TOULOUSE Cedex 9
Japan	Investigational Site Number : 3920002	Okayama-shi	Okayama
Japan	Investigational Site Number : 3920001	Shibuya-ku	Tokyo
Spain	Investigational Site Number : 7240001	Badalona	Catalunya [Cataluña]
Spain	Investigational Site Number : 7240002	Santander	Cantabria
United States	Gabrail Cancer Center Site Number : 8400001	Canton	Ohio
United States	City of Hope Site Number : 8400002	Duarte	California
United States	~Banner MD Anderson Cancer Center Site Number : 8400005	Gilbert	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Japan,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of adverse events (AEs)	Number of participants with adverse events	Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration)
Primary	Pharmacokinetic (PK) assessment: Ceoi	Concentration observed at the end of infusion (Ceoi)	Baseline to end of treatment (EOT) after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary	PK assessment: Cmax	Maximum concentration observed after the first infusion (Cmax)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary	PK assessment: tmax	Time to reach Cmax (tmax)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary	PK assessment: Clast	Last concentration observed above the lower limit of quantification after the first infusion (Clast)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary	PK assessment: tlast	Time of Clast (tlast)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary	PK assessment: Ctrough	Concentration observed just before treatment administration during repeated dosing (Ctrough)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary	PK assessment: AUClast	Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast) (AUClast)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary	PK assessment: AUC0 T	Area under the plasma concentration versus time curve calculated over the dosing interval T (168h or 336h) (AUC0 T)	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Secondary	Estimation of absolute bioavailability of isatuximab	Absolute bioavailability of isatuximab SC, expressed as a percentage, estimated from AUC0-168h obtained after intravenous (IV) and extravascular (EV) administration	Day 8
Secondary	Overall response rate (ORR)	ORR is the proportion of patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) using the IMWG response criteria	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary	Duration of response (DOR)	Time from the date of the first response to the date of first progressive disease (PD) or death, whichever happens first	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary	Time to response (TTR)	Time from the date of first study treatment to the first response	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary	Time to progression (TTP)	Time from date of first study treatment to date of first documentation of progressive disease	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary	Overall survival (OS)	Time from the date of first study treatment to date of death from any cause	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary	Clinical benefit rate (CBR)	Proportion of patients with sCR, CR, VGPR, PR or minimal response (MR) according to IMWG criteria	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary	Progression free survival (PFS)	Time from date of first study treatment to date of first documentation of progressive disease or death	From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary	Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires	Comparison of patient expectations and satisfaction will be assessed using Patient Expectations and Satisfaction Questionnaires before and after subcutaneous (SC) administration, where a score of 1 = not satisfied and a score of 5 = extremely satisfied	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)
Secondary	Immunogenicity: Anti drug antibody levels	Incidence of patients with anti drug antibodies against isatuximab	Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Secondary	Biomarker: Change in CD38 receptor occupancy	Change in CD38 receptor occupancy from baseline	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.