Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, First-in-human, Phase 1, Relapsed or Refractory, CC-92328
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).
Interventions
DRUGCC-92328
CC-92328
Sponsors
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 - Cmax | Day 1 to 9 weeks after last dose of study drug | Maximum serum concentration of drug. |
| Pharmacokinetics - Cmin | Day 1 to 9 weeks after last dose of study drug | Minimum serum concentration of drug. |
| Pharmacokinetics - AUC | Day 1 to 9 weeks after last dose of study drug | Area under the curve. |
| Pharmacokinetics - tmax | Day 1 to 9 weeks after last dose of study drug | Time to peak (maximum) serum concentration. |
| 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. |
| Pharmacokinetics - CL | Day 1 to 9 weeks after last dose of study drug | Total body clearance of the drug from the serum. |
| Pharmacokinetics - Vd | Day 1 to 9 weeks after last dose of study drug | Volume of distribution. |
| Pharmacokinetics - Accumulation index of CC-92328 | Day 1 to 9 weeks after last dose of study drug | Calculated from the serum concentration-time data of CC-92328 using non-compartment methods. |
| 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. |
| 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. |
| Pharmacokinetics - t1/2 | Day 1 to 9 weeks after last dose of study drug | Half-life. |
| Preliminary Efficacy - Time to response | Up 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 response | Up 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. |
Countries
Canada, Spain, United States
Outcome results
None listed