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

Overview

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

• Biological OriCAR-017
  GPCRC5D-directed chimeric antigen receptor modified T cells

Primary outcome measures

• Maximum tolerated dose of OriCAR-017-P1 [Time frame: Up to 28 days]
• Dose-limiting toxicity (DLT) [Time frame: Up to 28 days]

Secondary outcome measures (5)

• Objective Response Rate [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: From date of randomization until the date of first documented date of death from any cause, assessed up to 15 years]

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:

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 5 centers

• The First Affiliated Hospital College of Medicine Zhejiang University — Hangzhou
• Beijing GoBroad Hospital — Beijing
• The First Affiliated Hospital with Nanjing Medical University — Nanjing
• Tongji Hospital of Tongji University — Shanghai
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT06182696 · OriCAR-017-P1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗