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

Phase 1

Completed

• Conditions: Multiple Myeloma
• Interventions: Biological: CC-98633

• Registration Number: NCT04394650
• Lead Sponsor: Juno Therapeutics, a Subsidiary of Celgene

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-14
• Study First Submitted QC: 2020-05-14
• Study First Posted: 2020-05-19
• Study Start: 2020-08-18
• Status Verified: 2024-07
• Primary Completion: 2024-07-03
• Study Completion: 2024-07-03
• Last Update Submitted: 2024-07-24
• Last Update Posted: 2024-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. Age ≥ 18 years.

2. Signed written informed consent prior to any study procedure.

3. Relapsed and/or refractory multiple myeloma (MM).

   1. 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.
   2. Part A and Part B Cohort A: Subjects must have confirmed at least 3 prior antimyeloma treatment regimens.
   3. 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.
   4. 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.

4. Measurable disease

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

6. Adequate organ function

Exclusion Criteria

1. Known active or history of central nervous system (CNS) involvement of MM
2. Active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, or clinically significant amyloidosis
3. Prior treatment with CAR T-cell or another genetically modified T-cell therapy
4. Part A and Part B Cohort A only: Prior treatment with investigational therapy directed at BCMA
5. Uncontrolled or active infection
6. Active autoimmune disease requiring immunosuppressive therapy
7. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CC-98633	CC-98633	Subjects will receive CC-98633 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide).

Primary Outcome Measures

Name	Time	Method
Adverse Events (AEs)	From the time of informed consent and follow up to 2 years after infusion of CC-98633:	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.

Secondary Outcome Measures

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

Trial Locations

Locations (11)

Local Institution - 103; 🇺🇸 Birmingham, Alabama, United States

Local Institution - 111; 🇺🇸 Phoenix, Arizona, United States

Local Institution - 101; 🇺🇸 Westwood, Kansas, United States

Local Institution - 106; 🇺🇸 Buffalo, New York, United States

Local Institution - 109; 🇺🇸 Rochester, Minnesota, United States

Local Institution - 102; 🇺🇸 New York, New York, United States

Local Institution - 107; 🇺🇸 Chicago, Illinois, United States

Local Institution - 110; 🇺🇸 Stanford, California, United States

Local Institution - 104; 🇺🇸 New York, New York, United States

Local Institution - 105; 🇺🇸 Dallas, Texas, United States

Local Institution - 108; 🇺🇸 Charlotte, North Carolina, United States