OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM

OriCell Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Relapsed and/or Refractory Multiple Myeloma

Treatments: Biological: OriCAR-017

Study type: Interventional

Funder types: Industry

Identifiers

NCT06182696

OriCAR-017-P1

Details and patient eligibility

About

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

Full 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).

Enrollment: 83 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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83 participants in 1 patient group

OriCAR-017 ( GPCRC5D-directed chimeric antigen receptor modified T cells )

Experimental group

Description:

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.

Treatment:

Biological: OriCAR-017