A Study of CC-98633, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Participants With Relapsed and/or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a Phase 1, multicenter, open-label study of CC-98633, BCMA-Targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in participants with relapsed and/or refractory multiple myeloma. The study will consist of 2 parts: dose-escalation (Part A) and dose-expansion (Part B). The dose-escalation part (Part A) of the study is to evaluate the safety and tolerability of increasing dose levels of CC-98633 to establish a recommended Phase 2 dose RP2D(s); and the dose-expansion part (Part B) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of CC-98633 at the RP2D(s).

Official Title
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A Phase I, Multi Center, Open Label Study of CC-98633, BCMA Targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed and/or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: CC-98633


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Signed written informed consent prior to any study procedure. Relapsed and/or refractory multiple myeloma (MM). Subjects must have documented progressive disease as per International Myeloma Working Group (IMWG) criteria during or within 12 months of completing treatment with the last anti-myeloma treatment regimen before study entry. Also, subjects with confirmed progressive disease within 6 months prior to start of Screening and who are refractory (or non-responsive) to their most recent anti-myeloma treatment regimen afterwards will be also eligible. Part A and Part B Cohort A: Subjects must have confirmed at least 3 prior antimyeloma treatment regimens. Part B Cohort B only: Subjects must have received at least 1 but no greater than 3 prior antimyeloma treatment regimens, including a proteasome inhibitor and immunomodulatory agent. Subjects must have previously received all of the following therapies: i) Autologous stem cell transplant ii) A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or combination iii) Anti-CD38 (eg, daratumumab), either alone or combination Subjects in Cohort B do not require prior anti-CD38 antibody therapy. Measurable disease Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ function Exclusion Criteria: Known active or history of central nervous system (CNS) involvement of MM Active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, or clinically significant amyloidosis Prior treatment with CAR T-cell or another genetically modified T-cell therapy Part A and Part B Cohort A only: Prior treatment with investigational therapy directed at BCMA Uncontrolled or active infection Active autoimmune disease requiring immunosuppressive therapy History or presence of clinically significant CNS pathology such as seizure disorder, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CC-98633<br>Subjects will receive CC-98633 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide). | Biological: CC-98633<br>* Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to produce CC-98633. During CC-98633 production, subjects may receive bridging chemotherapy for disease control. Upon successful generation of CC-98633 product, subjects will receive treatment with CC-98633 therapy. Study treatment will include lymphodepleting chemotherapy followed by one dose of CC-98633 administered by intravenous (IV) injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) | incidence and severity of AEs. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. | From the time of informed consent and follow up to 2 years after infusion of CC-98633: | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | The proportion of subjects with a partial response (PR) or better by the IMWG criteria. | Up to 2 years after CC-98633 infusion | 
| Complete Response (CR) Rate | The proportion of subjects achieving stringent CR or CR. | Up to 2 years after CC-99633 infusion | 
| Duration of response (DOR) | The time from first response (sCR, CR, VGPR, or PR) to progressive disease (PD) or death. | Up to 2 years after CC-98633 infusion | 
| Time to response (TTR) | Time from CC-98633 infusion to the first documentation of response (sCR, CR, VGPR or PR). | Up to 2 years after CC-98633 infusion | 
| Time to complete response (TTCR) | Time from CC-98633 infusion to the first documentation of sCR or CR | Up to 2 years after CC-98633 infusion | 
| Progression free survival (PFS) | Time from CC-98633 infusion to the first documentation of PD, or death from any cause, whichever occurs first | Up to 2 years after CC-98633 infusion | 
| Overall survival (OS) | Time from CC-98633 infusion to death | Up to 2 years after CC-98633 infusion | 
| Pharmacokinetics - maximum serum concentration (Cmax) | Maximum blood concentration | Up to 2 years after CC-98633 infusion | 
| Pharmacokinetics -time to peak serum concentration (tmax) | Time to peak (maximum) blood concentration | Up to 2 years after CC-98633 infusion | 
| Pharmacokinetics - Area under curve (AUC) | Area under the curve | Up to 2 years after CC-98633 infusion | 
| Very good partial response (VGPR) or better | Is define as proportion of subjects achieving sCR, CR, or VGPR | Up to 2 years after CC-98633 infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Myeloma, Myeloma Multiple, CC-98633, BCMA, CAR-T, CART, BCMA CART, BCMA CAR-T