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

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

Detailed Description
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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).

Official Title
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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

Conditions
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Relapsed and/or Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: OriCAR-017


Participation Criteria
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Eligibility Criteria
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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: Serum M protein >5 g/L; Urine M protein level >200 mg/24 hour; Serum free light chain (sFLC) >100 mg/L and K/λ FLC ratio is abnormal; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: OriCAR-017 ( GPCRC5D-directed chimeric antigen receptor modified T cells )<br>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<br>* GPCRC5D-directed chimeric antigen receptor modified T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of OriCAR-017-P1 | 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) | tolerability | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | 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) | 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) | 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) | 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 | 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 |