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Study to Evaluate the Safety and Tolerability of CC-92328 in Participants With Relapsed and/or Refractory Multiple Myeloma

Phase 1
Terminated
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT04975399
Lead Sponsor
Celgene
Brief Summary

This Phase 1, first-in-human (FIH), clinical study of CC-92328 will explore the safety, tolerability and preliminary biological and clinical activity of CC-92328 as a single-agent in the setting of relapsed and/or refractory multiple myeloma (R/R MM). The study will be conducted in two parts: monotherapy dose escalation (Part A) and monotherapy dose expansion (Part B).

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
26
Inclusion Criteria

Participants must satisfy the following criteria to be enrolled in the study:

  1. must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
  2. willing and able to adhere to the study visit schedule and other protocol requirements.
  3. Participant is ≥ 18 years of age the time of signing the ICF.
  4. Participant has a history of multiple myeloma (MM) with relapsed and/or refractory disease who have failed or who are ineligible or intolerant to available therapies that may provide clinical benefit.
  5. Have documented disease progression on or within 12 months from the last dose of their last myeloma therapy.
  6. Participant must have measurable disease.
  7. Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  8. Females of childbearing potential (FCBP) must commit to true abstinence from heterosexual contact or agree to use at least one method of highly effective contraception without interruption from screening to at least 12 weeks after the last dose of CC-92328
  9. Males must practice true abstinence or agree to use a condom
  10. FCBP and males must avoid conceiving from signing the ICF, while participating in the study, during dose interruptions, and for at least 12 weeks after the last dose of CC-92328.
Exclusion Criteria

The presence of any of the following will exclude a participant from enrollment:

  1. Participant has symptomatic central nervous system involvement of MM.
  2. Participant had a prior autologous stem cell transplant ≤ 90 days prior to starting CC-92328.
  3. Participant had a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 12 months prior to starting CC-92328.
  4. Participant had prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting CC-92328, whichever is shorter.
  5. Participant is a pregnant or lactating female.
  6. Participant received live virus vaccines within at least 4 weeks prior to starting study drug.
  7. Participant has known active human immunodeficiency virus (HIV) infection.
  8. Participant has active hepatitis B or C (HBV/HCV) infection.
  9. Participant weight is ≤ 40 kg at screening.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Administration of CC-92328CC-92328CC-92328 administered intravenously in 28-day cycles
Primary Outcome Measures
NameTimeMethod
Maximum Tolerated Dose (MTD)Up to 12 weeks after the last dose

Defined as the highest dose at which less than 33% of the population treated with CC-92328 experience a dose-limiting toxicity (DLT) in the first cycle and at least 6 evaluable participants have been treated at this dose level.

Incidence of Adverse Events (AEs)Up to 12 weeks after the last dose

Type, frequency, seriousness, severity and relationship of AEs to CC-92328.

Dose-Limiting Toxicities (DLTs)Up to 28 days after the first dose

Are defined as toxicities that meet the protocol-specified criteria occurring within the DLT assessment window (Cycle 1, Days 1 to 28) except those that are clearly and incontrovertibly due to the underlying disease or extraneous causes.

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics - CmaxDay 1 to 9 weeks after last dose of study drug

Maximum serum concentration of drug.

Pharmacokinetics - t1/2Day 1 to 9 weeks after last dose of study drug

Half-life.

Frequency of Anti-CC92328 antibodies (ADA)Day 1 to 9 weeks after last dose of study drug

Determined using a validated bridging immunoassay with electrochemiluminescence detection.

Preliminary Efficacy - Time to responseUp to approximately 2 years

Defined as the time from the first CC-92328 dose date to the date of first documented response (PR or better).

Preliminary Efficacy - Duration of responseUp to approximately 2 years

Defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.

Preliminary Efficacy - Overall Survival (OS)Up to approximately 2 years

Defined as the time from the first dose of CC-92328 to death from any cause.

Pharmacokinetics - CLDay 1 to 9 weeks after last dose of study drug

Total body clearance of the drug from the serum.

Pharmacokinetics - VdDay 1 to 9 weeks after last dose of study drug

Volume of distribution.

Presence of Anti-CC92328 antibodies (ADA)Day 1 to 9 weeks after last dose of study drug

Determined using a validated bridging immunoassay with electrochemiluminescence detection.

Preliminary Efficacy - Overall Response Rate (ORR)Up to approximately 2 years

Defined as the proportion of participants who achieve a partial response (PR) or better according to IMWG response criteria.

Preliminary Efficacy - Progression-free Survival (PFS)Up to approximately 2 years

Defined as the time from the first dose of CC-92328 to pharmacodynamics (PD) or death from any cause, whichever occurs first.

Pharmacokinetics - tmaxDay 1 to 9 weeks after last dose of study drug

Time to peak (maximum) serum concentration.

Pharmacokinetics - AUCDay 1 to 9 weeks after last dose of study drug

Area under the curve.

Pharmacokinetics - CminDay 1 to 9 weeks after last dose of study drug

Minimum serum concentration of drug.

Pharmacokinetics - Accumulation index of CC-92328Day 1 to 9 weeks after last dose of study drug

Calculated from the serum concentration-time data of CC-92328 using non-compartment methods.

Trial Locations

Locations (15)

Local Institution - 302

🇪🇸

Pamplona, Navarra, Spain

Local Institution - 204

🇨🇦

Edmonton, Alberta, Canada

Local Institution - 105

🇺🇸

Scottsdale, Arizona, United States

Local Institution - 201

🇨🇦

Calgary, Alberta, Canada

Local Institution - 301

🇪🇸

Badalona, Spain

Local Institution - 304

🇪🇸

Santander, Spain

Local Institution - 205

🇨🇦

Montreal, Quebec, Canada

Local Institution - 303

🇪🇸

Salamanca, Spain

Local Institution - 108

🇺🇸

New York, New York, United States

Local Institution - 107

🇺🇸

New York, New York, United States

Local Institution - 101

🇺🇸

Milwaukee, Wisconsin, United States

Local Institution - 203

🇨🇦

Halifax, Nova Scotia, Canada

Local Institution - 106

🇺🇸

Tampa, Florida, United States

Local Institution - 104

🇺🇸

Birmingham, Alabama, United States

Local Institution - 202

🇨🇦

Toronto, Ontario, Canada

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