Clinical trial NCT06182696: OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed and/or Refractory Multiple Myeloma
Lead sponsor: OriCell Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-12-27
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: Maximum tolerated dose of OriCAR-017-P1
timeFrame: Up to 28 days
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Objective Response Rate
timeFrame: 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
measure: Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)
timeFrame: 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
measure: Antitumor efficacy-Progression-free survival (PFS)
timeFrame: 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
measure: Antitumor efficacy-Duration of response (DOR)
timeFrame: 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
measure: Long term survival follow up
timeFrame: From date of randomization until the date of first documented date of death from any cause, assessed up to 15 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital College of Medicine Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: Beijing GoBroad Hospital
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
Study officials:
References: