Relapsed and/or Refractory Multiple Myeloma
Conditions
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).
Interventions
BIOLOGICALOriCAR-017
GPCRC5D-directed chimeric antigen receptor modified T cells
Sponsors
OriCell Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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: 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose of OriCAR-017-P1 | 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) | Up to 28 days | tolerability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | The period from the day when the subject receives the infusion of cells to the first recorded tumor progression |
| 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 | Objective response is defined as the participants with a partial response (PR) or better by the RECIST1.1 criteria. |
| 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 | The period from randomization until the date of death |
| 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 | 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 |
| 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 | CAR-GPRC5D DNA in peripheral blood detected by q-PCR at each visit after infusion |
Countries
China
Contacts
Primary ContactHE Huang, MD
Outcome results
None listed