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

Relapsed and/or Refractory Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06182696
• Other study ID #: OriCAR-017-P1
• Status: Enrolling by invitation
• Phase: Phase 1/Phase 2
• Start date: October 26, 2023
• Est. completion date: August 31, 2028

Study information

• Verified date: April 2024
• Source: OriCell Therapeutics Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 83
• Est. completion date: August 31, 2028
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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/? 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Relapsed and/or Refractory Multiple Myeloma

Intervention

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

Locations

Country	Name	City	State
China	The First Affiliated Hospital College of Medicine Zhejiang University	Hangzhou	Zhejiang
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing
China	Tongji Hospital of Tongji University	Shanghai
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan

Sponsors (1)

Lead Sponsor	Collaborator
OriCell Therapeutics Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Dose-limiting toxicity (DLT)	tolerability	Up to 28 days
Secondary	Objective Response Rate	Objective response is defined as the participants with a partial response (PR) or better by the RECIST1.1 criteria.	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
Secondary	Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)	CAR-GPRC5D DNA in peripheral blood detected by q-PCR at each visit after infusion	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
Secondary	Antitumor efficacy-Progression-free survival (PFS)	The period from the day when the subject receives the infusion of cells to the first recorded tumor progression	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
Secondary	Antitumor efficacy-Duration of response (DOR)	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	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
Secondary	Long term survival follow up	The period from randomization until the date of death	From date of randomization until the date of first documented date of death from any cause, assessed up to 15 years