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

Study Overview
=================
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).

Official Title
-----------------
A Phase 1, Multi-center, Open-label, Dose Finding Study of CC-92328 in Subjects With Relapsed and/or Refractory Multiple Myeloma

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: CC-92328


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must satisfy the following criteria to be enrolled in the study: must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted. willing and able to adhere to the study visit schedule and other protocol requirements. Participant is ≥ 18 years of age the time of signing the ICF. 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. Have documented disease progression on or within 12 months from the last dose of their last myeloma therapy. Participant must have measurable disease. Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. 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 Males must practice true abstinence or agree to use a condom 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: Participant has symptomatic central nervous system involvement of MM. Participant had a prior autologous stem cell transplant ≤ 90 days prior to starting CC-92328. Participant had a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 12 months prior to starting CC-92328. Participant had prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting CC-92328, whichever is shorter. Participant is a pregnant or lactating female. Participant received live virus vaccines within at least 4 weeks prior to starting study drug. Participant has known active human immunodeficiency virus (HIV) infection. Participant has active hepatitis B or C (HBV/HCV) infection. Participant weight is ≤ 40 kg at screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of CC-92328<br>CC-92328 administered intravenously in 28-day cycles | Drug: CC-92328<br>* CC-92328<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting Toxicities (DLTs) | 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. | Up to 28 days after the first dose | 
| Maximum Tolerated Dose (MTD) | 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. | Up to 12 weeks after the last dose | 
| Incidence of Adverse Events (AEs) | Type, frequency, seriousness, severity and relationship of AEs to CC-92328. | Up to 12 weeks after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary Efficacy - Overall Response Rate (ORR) | Defined as the proportion of participants who achieve a partial response (PR) or better according to IMWG response criteria. | Up to approximately 2 years | 
| Preliminary Efficacy - Time to response | Defined as the time from the first CC-92328 dose date to the date of first documented response (PR or better). | Up to approximately 2 years | 
| Preliminary Efficacy - Duration of response | Defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first. | Up to approximately 2 years | 
| Preliminary Efficacy - Progression-free Survival (PFS) | Defined as the time from the first dose of CC-92328 to pharmacodynamics (PD) or death from any cause, whichever occurs first. | Up to approximately 2 years | 
| Preliminary Efficacy - Overall Survival (OS) | Defined as the time from the first dose of CC-92328 to death from any cause. | Up to approximately 2 years | 
| Pharmacokinetics - Cmax | Maximum serum concentration of drug. | Day 1 to 9 weeks after last dose of study drug | 
| Pharmacokinetics - Cmin | Minimum serum concentration of drug. | Day 1 to 9 weeks after last dose of study drug | 
| Pharmacokinetics - AUC | Area under the curve. | Day 1 to 9 weeks after last dose of study drug | 
| Pharmacokinetics - tmax | Time to peak (maximum) serum concentration. | Day 1 to 9 weeks after last dose of study drug | 
| Pharmacokinetics - t1/2 | Half-life. | Day 1 to 9 weeks after last dose of study drug | 
| Pharmacokinetics - CL | Total body clearance of the drug from the serum. | Day 1 to 9 weeks after last dose of study drug | 
| Pharmacokinetics - Vd | Volume of distribution. | Day 1 to 9 weeks after last dose of study drug | 
| Pharmacokinetics - Accumulation index of CC-92328 | Calculated from the serum concentration-time data of CC-92328 using non-compartment methods. | Day 1 to 9 weeks after last dose of study drug | 
| Presence of Anti-CC92328 antibodies (ADA) | Determined using a validated bridging immunoassay with electrochemiluminescence detection. | Day 1 to 9 weeks after last dose of study drug | 
| Frequency of Anti-CC92328 antibodies (ADA) | Determined using a validated bridging immunoassay with electrochemiluminescence detection. | Day 1 to 9 weeks after last dose of study drug | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Multiple Myeloma, First-in-human, Phase 1, Relapsed or Refractory, CC-92328