Anti-GPRC5D CAR-T Cells (CT071) in Participants With RRMM or RRpPCL

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma; Primary Plasma Cell Leukemia
• Intervention / Treatment: Biological: CT071

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.

• Study Type: Interventional
• Enrollment (Estimated): 166
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: CARsgen US; Phone Number: CentralNumber; Email: clinicalUS@carsgen.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1; Dose Escalation followed a dose expansion.	Biological: CT071; a single CAR-T infusion of CT071
Experimental: Phase 2; Single group of patients for each indication (rrMM, RRpPCL).	Biological: CT071; a single CAR-T infusion of CT071

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Evaluation of the Safety of CT071 and determination of Maximum Tolerated Dose (MTD).	Frequency, type, and severity of AEs (SAEs, AESIs, laboratory abnormalities).	Day 1 - Month 24
Phase 2: Objective response rate	Objective response rate (ORR) per IMWG by IRC read; percentage of participants achieving confirmed PR or better per IMWG 2016 consensus criteria.	Day 1 - Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and 2: Evaluate additional clinical efficacy outcomes	Overall Response Rate/Best Overall Response Rate by investigator (by IMWG stringent complete response/sCR, complete response/CR, very good partial response/VGPR, and partial response/PR by IRC and investigator assessment).	Day 1 - Month 24
Phase 1 and 2: Evaluate additional clinical efficacy outcomes	Duration of Response by IMWG (stringent complete response/sCR, complete response/CR, very good partial response/VGPR, and partial response/PR by IRC and investigator assessment).	Day 1 - Month 24
Phase 1 and 2: Evaluate additional clinical efficacy outcomes	Progression Free Survival by investigator assessment	Day 1 - Month 24
Phase 1 and 2: Evaluate additional clinical efficacy outcomes	Overall Survival	Day 1 - Month 24
Phase 2: Evaluate additional Safety of CT071.	Frequency, type, and severity of AEs (SAEs, AESIs, laboratory abnormalities).	Day 1 - Month 24
Phase 1 and 2: Assess immunogenicity of CT071	Percentage of patients with anti-CT071 drug antibodies	Day 1 - Month 60
Phase 1 and 2: Evaluate PK profile of CT071	CAR transgene copy peak value	Day 1 - Month 60
Phase 1 and 2: Evaluate PK profile of CT071	CAR transgene copy number persistence	Day 1 - Month 60
Phase 1 and 2: Evaluate PK profile of CT071	CAR transgene copy AUC	Day 1 - Month 60

Collaborators and Investigators

• Sponsor: CARsgen Therapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; CAR-T; GPRC5D; hematologic cancer; Primary plasma cell myeloma; CT071; anti-GPRC5D; genetically modified T-cells
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia; Leukemia, Plasma Cell
• Other Study ID Numbers: CT071-HM-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No