A Study to Investigate Subcutaneous Isatuximab in Combination With Weekly Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma

Official title

A Single-arm, Open-label, Phase 2 Study Evaluating Subcutaneous Administration of Isatuximab, Administered by an On Body Delivery System, in Combination With Weekly Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM)

Overview

The primary purpose of this study is to assess the efficacy (overall response rate) of subcutaneous (SC) via on body delivery system (SC-OBDS) isatuximab in combination with weekly carfilzomib and dexamethasone (Kd) in adult participants with RRMM having received 1 to 3 prior lines of therapy.

Detailed description

The duration of the study for a participant will include a period for screening of up to 28 days, a study treatment period of 12 months (except early discontinuation), the end-of-treatment (EOT) visit about 30 days after the last dose of study treatment, and a study follow-up period until death or the final study cut-off date. A cycle duration is 28 days. After study treatment discontinuation, participants will return to the study site 30 days after the last dose of study treatment for the EOT visit or before further anti-myeloma therapy initiation, whichever comes first.

Interventions

• Drug Isatuximab SC-OBDS
  Pharmaceutical form:Solution for SC-OBDS administration-Route of administration:SC-OBDS
• Drug Montelukast
  Pharmaceutical form:As per local commercial product-Route of administration:Oral
• Drug Dexamethasone
  Pharmaceutical form:As per local commercial product-Route of administration:Oral or IV
• Drug Acetaminophen
  Pharmaceutical form:As per local commercial product-Route of administration:Oral or IV
• Drug Diphenhydramine
  Pharmaceutical form:As per local commercial product-Route of administration:Oral (as premedication) or IV/oral equivalent (for management of infusion reaction)
• Drug Methylprednisolone
  Pharmaceutical form:As per local commercial product-Route of administration:IV
• Drug Carfilzomib
  Pharmaceutical form:As per local commercial product-Route of administration:IV

Primary outcome measures

• Overall response rate (ORR) [Time frame: 6 months after the Last Participant In (LPI) i.e., approximately 32 months]

Secondary outcome measures (12)

• Number of participants with infusion reactions (IRs) [Time frame: From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months]
• Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities (per NCI-CTCAE grade or PCSA if NCI-CTCAE scale is not applicable) [Time frame: From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months]
• Number of participants with injection site reactions (ISRs) [Time frame: From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months]
• CR or better [Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months]
• VGPR or better [Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months]
• Duration of response (DOR) [Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months]
• Time to first response (TT1R) [Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months]
• Time to best response (TTBR) [Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months]
• Patient experience and Satisfaction Questionnaire v2 (PESQ v2) [Time frame: Cycle 3/Day 15 and Cycle 6/Day 15]
• Positivity titer of anti-drug antibodies (ADA) in a subset of approximately 30 participants [Time frame: From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e, approximately up to 15 months (1 cycle = 28 days)]
• Maximum observed concentration (Cmax) of isatuximab in a subset of approximately 30 participants [Time frame: Multiple timepoints in Cycle 1 (1 cycle = 28 days)]
• Cumulative area under the curve over the first 4 weeks of isatuximab treatment (AUC4 weeks) in a subset of approximately 30 participants [Time frame: Multiple timepoints in Cycle 1 (1 cycle = 28 days)]

Eligibility criteria

Inclusion criteria

• Participants must have a documented diagnosis of MM.
• Participants with measurable disease defined as at least one of the following:

• Serum M-protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
• Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
• 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).
• Participants with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy.
• Contraceptive use by \[men and women\] should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• Male participants agree to practice true abstinence or agree to use contraception while receiving study treatment, during dose interruptions and at least 5 months following study treatment discontinuation, even if has undergone a successful vasectomy.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either is not a female of childbearing potential (FCBP XE " FCBP " \\f Abbreviation \\t "female of childbearing potential" ) or agrees to practice complete abstinence or use contraception.
• Capable of giving signed informed consent.

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• Primary refractory MM defined as participants who have never achieved at least a minimal response (MR) with any treatment during the disease course.
• Participants with prior anti-CD38 treatment if: a) administered < 6 months before first isatuximab administration or, b) intolerant to the anti-CD38 previously received.
• Participants who are refractory to carfilzomib.
• Known history of allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib), prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), polysorbate 80, or any of the components (active substance or excipient) of study treatment that are not amenable to premedication with steroids, or intolerance to arginine and Poloxamer 188 that would prohibit further treatment with these agents.
• Participants with contraindication to dexamethasone and/or to carfilzomib.
• Any anti-myeloma drug treatment within 14 days before the first isatuximab administration, including dexamethasone.
• Prior allogenic HSC transplant with active graft versus host disease (GvHD XE " GvHD " \\f Abbreviation \\t "graft versus host disease" ) (GvHD any grade and/or being under immunosuppressive treatment within the last 2 months).
• Any major procedure within 14 days before the first isatuximab administration: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy.
• Vaccination with a live vaccine within 4 weeks before the first isatuximab administration. Seasonal flu vaccines that do not contain live virus are permitted.
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 34 centers

• Mayo Clinic in Arizona - Phoenix- Site Number : 8400058 — Phoenix
• Los Angeles Hematology Oncology Medical Group- Site Number : 8400027 — Los Angeles
• Private Practice - Dr. James R. Berenson- Site Number : 8400044 — West Hollywood
• Smilow Cancer Center at Yale-New Haven- Site Number : 8400020 — New Haven
• Maryland Oncology Hematology- Site Number : 8400038 — Washington D.C.
• Life Clinical Trials - Coral Springs- Site Number : 8400055 — Coral Springs
• Center for Rheumatology, Immunology and Arthritis- Site Number : 8400031 — Fort Lauderdale
• Mayo Clinic in Florida- Site Number : 8400002 — Jacksonville
• … and 26 more centers

Identifiers

NCT: NCT06356571 · LPS18183 · U1111-1298-7348

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗