Clinical trial NCT06333509: Anti-GPRC5D CAR-T Cells (CT071) in Participants With RRMM or RRpPCL
Official title: A Phase 1/2 Open Label Study to Evaluate the Safety and Efficacy of CT071, an Autologous Anti-GPRC5D CAR T, in Relapsed/Refractory Multiple Myeloma (RRMM) or Relapsed/Refractory Primary Plasma Cell Leukemia (RRpPCL)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Primary Plasma Cell Leukemia
Keywords: CAR-T
Multiple Myeloma
Primary plasma cell myeloma
CT071
GPRC5D
anti-GPRC5D
genetically modified T-cells
hematologic cancer
Lead sponsor: CARsgen Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-03-27
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1; Dose escalation followed by dose expansion Phase 2; Single group of each indication will be dosed at the recommended dose level from Phase 1.
Primary purpose: TREATMENT

Brief summary: A Phase 1/2 Open label, multicenter, clinical trial of autologous CAR T-cell therapy targeting GPRC5D, in participants with relapsed/refractory multiple myeloma or relapsed/refractory primary plasma cell leukemia.

Detailed description: This is an open-label, multicenter, Phase 1/2 trial of CT071 in adult participants with relapsed or refractory multiple myeloma (RRMM) or relapsed or refractory primary plasma cell leukemia (RRpPCL).

The study will be conducted in two phases. Phase 1 of the study will be dose escalation followed by dose expansion. After recommended Phase 2 dose is identified in Phase 1, the enrollment of Phase 2 will start. Following consent, enrolled subjects will undergo apheresis to collect cells for manufacture of the CAR-T cells. Following the manufacture of the CAR-T cells, subjects will receive lymphodepletion prior to CAR T-cell infusion. All subjects who complete the study, as well as those who withdraw from the study after receiving CAR T-cell infusion for reasons other than death or meeting the early termination criteria, will be asked to undergo a 15-year long-term follow-up.

Eligibility criteria: Inclusion Criteria:

* Voluntarily signed consent;
* Age of ≥ 18;
* Willing and able to adhere to trial visit schedule and other protocol requirements
* Received sufficient prior lines of therapy;
* RRMM participants must have received treatment with at least one proteasome inhibitor, one IMiD and CD38 anti body, must be refractory to the last line of therapy, must have achieved a response (PR or better) to a least 1 prior treatment line;
* RRpPCL participants must have received at least one prior line of therapy.
* Participants must have documented diagnosis of RRMM or RRpPCL.
* The participants should have measurable disease.
* Estimated life expectancy \> 12 weeks;
* ECOG performance score 0-1;
* Participants should have bone marrow reserve, renal and hepatic functions;
* Sufficient venous access for apheresis collection, and no other contraindications to apheresis;
* Must be able to stop any anticancer therapy for planned apheresis collection
* Women of childbearing age must undergo a serum pregnancy test with negative results before screening, and are willing to use effective and reliable method of contraception for at least 12 months after T cell infusion;
* Men must be willing to use effective and reliable method of contraception for at least 12 months after T cell infusion.

Exclusion Criteria:

* Any significant condition(s), laboratory abnormality or psychiatric illness that would impair the ability of the participant to receive or tolerate the planned treatment or in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
* Pregnant or lactating women;
* HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection;
* Any uncontrolled active infection;
* AEs from previous treatment that have not recovered;
* Participants who have had anti-GPRC5D targeted agents;
* Participants who have received autologous stem cell transplantation 12 weeks before apheresis;
* Participants who have received allogenic stem cell transplantation within 6 months of apheresis;
* Participants who have graft versus host disease (GvHD);
* Participants who have received steroids within 14 days of apheresis or lymphodepletion;
* Participants who have plasma cell leukemia secondary to multiple myeloma, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or clinically significant symptomatic immunoglobulin light chain (AL) amyloidosis with evidence of end-organ damage;
* Participants who have been administered live attenuated vaccine 4 weeks before apheresis or lymphodepletion;
* Participants who are allergic to fludarabine, cyclophosphamide, tocilizumab, dimethyl sulfoxide (DMSO) or CT071;
* Participants who have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
* Participants who require supplemental oxygen;
* Participants who have clinically significant pulmonary conditions;
* Participants who are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy;
* Participants with malignancies in addition to MM/pPCL;
* Participants who have central nervous system (CNS) metastases or CNS involvement;
* Participants with a history of stroke or seizures within 6 months prior to apheresis;
* Participants who have undergone major surgery 14 days prior to apheresis or within 28 days of CT071 administration.

Primary outcomes:
measure: Phase 1: Evaluation of the Safety of CT071 and determination of Maximum Tolerated Dose (MTD).
timeFrame: Day 1 - Month 24
measure: Phase 2: Objective response rate
timeFrame: Day 1 - Month 24
Secondary outcomes:
measure: Phase 1 and 2: Evaluate additional clinical efficacy outcomes
timeFrame: Day 1 - Month 24
measure: Phase 1 and 2: Evaluate additional clinical efficacy outcomes
timeFrame: Day 1 - Month 24
measure: Phase 1 and 2: Evaluate additional clinical efficacy outcomes
timeFrame: Day 1 - Month 24
measure: Phase 1 and 2: Evaluate additional clinical efficacy outcomes
timeFrame: Day 1 - Month 24
measure: Phase 2: Evaluate additional Safety of CT071.
timeFrame: Day 1 - Month 24
measure: Phase 1 and 2: Assess immunogenicity of CT071
timeFrame: Day 1 - Month 60
measure: Phase 1 and 2: Evaluate PK profile of CT071
timeFrame: Day 1 - Month 60
measure: Phase 1 and 2: Evaluate PK profile of CT071
timeFrame: Day 1 - Month 60
measure: Phase 1 and 2: Evaluate PK profile of CT071
timeFrame: Day 1 - Month 60
Other outcomes:
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