CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.

主要终点：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
次要终点：Objective Response Rate；Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)；Antitumor efficacy-Progression-free survival (PFS)；Antitumor efficacy-Duration of response (DOR)；Long term survival follow up

• OriCAR-017 ( GPCRC5D-directed chimeric antigen receptor modified T cells ) · EXPERIMENTAL · 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.

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