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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 83
- Locations
- 5
- Primary Endpoint
- Maximum tolerated dose of OriCAR-017-P1
Study Overview
Brief Summary
An open label, dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of OriCAR-017 in R/RMM
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
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.
Arms & Interventions
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.
Intervention: OriCAR-017 (Biological)
Outcomes
Primary Outcomes
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.
Dose-limiting toxicity (DLT)
Time Frame: Up to 28 days
tolerability
Secondary Outcomes
- Objective Response Rate(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-Duration of response (DOR)(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)
- Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)(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)
- Long term survival follow up(From date of randomization until the date of first documented date of death from any cause, assessed up to 15 years)
- Antitumor efficacy-Progression-free survival (PFS)(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)