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

NCT06182696 | Recruiting Phase 1

• 1 other identifier: OriCAR-017-P1
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Relapsed and/or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (5)

• Objective Response Rate

  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)

  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)

  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)

  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

  From date of randomization until the date of first documented date of death from any cause, assessed up to 15 years

Study Arms (1)

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.

Biological: OriCAR-017

Interventions

OriCAR-017 BIOLOGICAL

GPCRC5D-directed chimeric antigen receptor modified T cells

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: 18-75
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• OriCell Therapeutics Co., Ltd.: lead

Study Sites (5)

The First Affiliated Hospital College of Medicine Zhejiang University

Hangzhou, Zhejiang, 310003, China

RECRUITING

Beijing GoBroad Hospital

Beijing, China

NOT YET RECRUITING

The First Affiliated Hospital with Nanjing Medical University

Nanjing, China

NOT YET RECRUITING

Tongji Hospital of Tongji University

Shanghai, China

NOT YET RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, China

RECRUITING

Central Study Contacts

HE Huang, MD

CONTACT

0571-88208277; hehuangyu@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: December 27, 2023
• Study Start: October 26, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): August 31, 2028
• Last Updated: May 31, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)