OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM

May 30, 2024 updated by: OriCell Therapeutics Co., Ltd.

An Open Label,Multi-center Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Autologous T Cell Injection Targeting GPRC5D OriCAR-017 in Patients With Relapsed and/or Refractory Multiplemyeloma

An open label, dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of OriCAR-017 in R/RMM

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase I and Phase II, open-label, multi-center study to assess the safety, pharmacokinetics, and efficacy of GPRC5D directed chimeric antigen receptor modified T cells injection (OriCAR-017) in n patients with relapsed and/or refractory multiplemyeloma (R/RMM).

Study Type

Interventional

Enrollment (Estimated)

83

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China
        • Not yet recruiting
        • Beijing GoBroad Hospital
        • Contact:
          • Kai Hu
      • Nanjing, China
        • Not yet recruiting
        • The First Affiliated Hospital with Nanjing Medical University
        • Contact:
          • Jianyong Li
      • Shanghai, China
        • Not yet recruiting
        • Tongji Hospital of Tongji University
        • Contact:
          • Aibin Liang
      • Wuhan, China
        • Recruiting
        • Union Hospital Tongji Medical College Huazhong University of Science and Technology
        • Contact:
          • Heng Mei
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • Recruiting
        • The First Affiliated Hospital College of Medicine Zhejiang University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Main Inclusion Criteria:

  • Diagnosis of R/RMM according to the IMWG criteria;
  • Expected survival period is >12 weeks;
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or 2 at the time of ICF signature;

  • The expression of GPRC5D in bone marrow plasma cells membrane is more than 20% by flow cytometry and/or immunohistochemistry, multiple myeloma with measurable lesions, and at least one of the following criteria must be met:

    1. Serum M protein >5 g/L;
    2. Urine M protein level >200 mg/24 hour;
    3. Serum free light chain (sFLC) >100 mg/L and K/λ FLC ratio is abnormal;
    4. Primitive immature or monoclonal plasma cells >5% by bone marrow cytology or flow cytometry.
  • Subjects who had received at least 3 prior lines of therapy including (but not limited to) immunomodulatory drugs (IMiDs), proteasome inhibitors, anti-CD38 monoclonal antibodies, etc., but have failed treatment, including those who have experienced relapse (within 12 months), refractory or intolerant to the last line treatment regimen.

Main Exclusion Criteria:

  • Smoldering myeloma (asymptomatic)
  • Multiple myeloma with only extramedullary lesions;
  • Plasma cell leukemia;
  • Concurrent amyloidosis;
  • Central nervous system metastasis, leptomeningeal disease or metastatic central compression;
  • HBsAg or HbcAb is positive, and the quantitative detection of hepatitis B virus (HBV) DNA in peripheral blood is more than 100 copies/L; hepatitis C virus (HCV) antibody and HCV RNA in peripheral blood is positive; human immunodeficiency virus (HIV) antibody positive; syphilis antibody is positive at Screening; Cytomegalovirus DNA test is positive;
  • Had hypersensitivity or intolerance to any drug/excipient (including conditioning chemotherapy) used in this study;
  • Previously received treatment targeting GPRC5D, including but not limited to antibodies, ADC, or CAR-T;
  • Subjects who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks of Screening Visit or who plan to undergo ASCT during the study;
  • Any uncontrolled active infection within 4 weeks prior to ICF signing or leukapheresis requires parenteral antibiotic, antiviral, or antifungal treatment
  • Major surgery within 28 days prior to Screening Visit with the exception of a biopsy and an insertion of a central venous catheter or during the study;
  • Subjects who received allogeneic stem cell therapy;
  • Subjects complications or other conditions evaluated by investigators may affect compliance with the protocol or make them unsuitable to participate in this study;
  • Pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: OriCAR-017 ( GPCRC5D-directed chimeric antigen receptor modified T cells )

Phase I (Dose-Escalation) The subjects enrolled will be sequentially assigned to the corresponding dose level to determin the RP2D. The dose-escalation part of the study will adopt the the standard 3+3 design, wherein 3 dose levels are planned to be evaluated.

Phase I (Dose-Expansion) After determining the RP2D, one of the dose levels will be selected for further evaluation during the dose-expansion part. Up to 10 to 15 additional subjects who are diagnosed with relapsed/refractory MM will be enrolled to further explore the anti-tumor activity of Ori-CAR-017.

Phase II The Phase II part of the study will be initiated at the RP2D of OriCAR-017 which will be selected based on the clinical data obtained during the Phase I part of the study.
Biological: OriCAR-017
GPCRC5D-directed chimeric antigen receptor modified T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose of OriCAR-017-P1
Time Frame: Up to 28 days
The MTD is defined as the highest dose with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level.
Up to 28 days
Dose-limiting toxicity (DLT)
Time Frame: Up to 28 days
tolerability
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause or withdraw, whichever came first, assessed up to 2 Years
Objective response is defined as the participants with a partial response (PR) or better by the RECIST1.1 criteria.
From date of randomization until the date of first documented progression or date of death from any cause or withdraw, whichever came first, assessed up to 2 Years
Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause or withdraw, whichever came first, assessed up to 2 years
CAR-GPRC5D DNA in peripheral blood detected by q-PCR at each visit after infusion
From date of randomization until the date of first documented progression or date of death from any cause or withdraw, whichever came first, assessed up to 2 years
Antitumor efficacy-Progression-free survival (PFS)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
The period from the day when the subject receives the infusion of cells to the first recorded tumor progression
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Antitumor efficacy-Duration of response (DOR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
The period from the first evaluation of sCR or CR or VGPR or PR or MR to the first evaluation of PD or death of any cause
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Long term survival follow up
Time Frame: From date of randomization until the date of first documented date of death from any cause, assessed up to 15 years
The period from randomization until the date of death
From date of randomization until the date of first documented date of death from any cause, assessed up to 15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OriCell Therapeutics Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2023

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

August 31, 2028

Study Registration Dates

First Submitted

December 11, 2023

First Submitted That Met QC Criteria

December 26, 2023

First Posted (Actual)

December 27, 2023

Study Record Updates

Last Update Posted (Actual)

May 31, 2024

Last Update Submitted That Met QC Criteria

May 30, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OriCAR-017-P1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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