OriCAR-017 for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: OriCell Therapeutics Co., Ltd.

Must not be taking: Bendamustine

Disqualifiers: HIV, Active Hepatitis, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

81 Participants Needed

Trial Summary

What is the purpose of this trial?

The is a first clinical study for Oricell Therapeutics Inc. in the United States to evaluate the safety, PK, PD and preliminary efficacy of our anti-GPRC5D cell product (OriCAR-017) in subjects with relapsed/refractory multiple myeloma. RIGEL Study

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain treatments like Bendamustine should not have been received within a year before the screening.

What data supports the effectiveness of the treatment OriCAR-017 for multiple myeloma?

Research shows that the OriCAR-017 treatment, which targets the GPRC5D protein on multiple myeloma cells, has been effective in early studies, with all 10 patients in one study showing positive responses. This suggests it could be a promising option for patients who have not responded to other treatments. ^{1 2 3 4 5}

Is OriCAR-017 (GPRC5D-CAR-T) safe for humans?

Preliminary studies suggest that OriCAR-017, a CAR T-cell therapy targeting GPRC5D, is generally safe for patients with multiple myeloma, as no significant safety concerns were reported in early trials. ^{1 2 3 4 5}

What makes the OriCAR-017 treatment unique for multiple myeloma?

OriCAR-017 is a novel CAR T-cell therapy that targets the GPRC5D protein on myeloma cells, offering a new approach for patients who have relapsed or are resistant to existing BCMA-targeted therapies. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for adults aged 18-75 with relapsed/refractory multiple myeloma, who have tried at least three prior treatments and are refractory to the last one. They must meet specific criteria based on their type of myeloma protein levels and have a life expectancy over 12 weeks.

Inclusion Criteria

I have been diagnosed with multiple myeloma according to the latest criteria.

Expected survival period is >12 weeks

One of the following criteria must be met: If IgG type MM, then serum M protein >10 g/L; if IgA, IgD, IgE or IgM type MM, then serum M protein >5 g/L; Urine M protein level >200 mg/24 hour; If light chain type MM, then serum free light chain (sFLC) >100 mg/L and K/λ FLC ratio is abnormal; Extramedullary lesions (>1 cm for diameter of the short axis); For Phase I (dose-escalation) - Subjects who had received at least 3 prior lines of therapy, had previous exposure to BCMA-Ag+ therapies, and were refractory to the last line of therapy; For Phase I (dose-expansion) and Phase II: Subjects with previous exposure to BCMA directed therapies including BCMA bispecific antibody, BCMA antibody directed conjugate, and BCMA-CAR-T; Subjects with adequate hematologic, renal, hepatic, pulmonary and cardiac function; Subject and partners willing to take and or use effective contraceptive measures until 2 years post IMP infusion

Exclusion Criteria

I received Bendamustine treatment a year ago.

I had or plan to have a stem cell transplant within 2 months of joining the study.

I currently have an infection that is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase I dose escalation stage involving three doses as a single IV infusion with up to 18 evaluable subjects

4 weeks

Multiple visits for dose administration and monitoring

Dose Expansion

Dose expansion stage with 10-15 evaluable subjects to further assess safety and efficacy

4 weeks

Multiple visits for dose administration and monitoring

Phase II

Phase II stage with up to 48 evaluable subjects to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy

Up to 2 years

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Regular follow-up visits

Treatment Details

Interventions

• OriCAR-017

Trial Overview The RIGEL Study is testing OriCAR-017, an anti-GPRC5D cell product by Oricell Therapeutics Inc., focusing on its safety, how it's processed in the body (PK/PD), and initial effectiveness in treating multiple myeloma patients.

Participant Groups

Group I: OriCAR-017 Experimental Treatment 1 Intervention

Single OriCAR-017 infusion

OriCAR-017 is already approved in China, United States for the following indications:

Approved in China as OriCAR-017 for:

• Relapsed/Refractory Multiple Myeloma

Approved in United States as OriCAR-017 for:

• Relapsed/Refractory Multiple Myeloma

Who Is Running the Clinical Trial?

OriCell Therapeutics Co., Ltd.

Lead Sponsor

Trials

5

Recruited

330+

Findings from Research

GPRC5D-targeted CAR T-cell therapy (OriCAR-017) showed promising efficacy in treating relapsed or refractory multiple myeloma, with a 100% overall response rate among 10 patients, including 60% achieving a stringent complete response.

The therapy demonstrated a favorable safety profile, with no serious adverse events or treatment-related deaths reported, although common grade 3 adverse effects included neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial. Zhang, M., Wei, G., Zhou, L., et al.[2023]

In a phase II study involving 33 patients with relapsed or refractory multiple myeloma, anti-GPRC5D CAR T-cell therapy demonstrated a high overall response rate of 91%, with significant responses even in patients previously treated with anti-BCMA CAR T-cell therapy.

The treatment was associated with manageable safety concerns, including common grade 3 or higher hematologic toxicities and cytokine release syndrome, indicating that while there are risks, the therapy is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase Ⅱ Trial. Xia, J., Li, H., Yan, Z., et al.[2023]

In a phase 1 study involving 17 heavily pretreated multiple myeloma patients, GPRC5D-targeted CAR T-cell therapy (MCARH109) demonstrated a 71% overall response rate, including responses in patients who previously relapsed after BCMA CAR T-cell therapy.

The maximum tolerated dose was determined to be 150×10^6 CAR T cells, with significant side effects observed at higher doses, indicating a need for careful dose management to minimize severe adverse events like cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GPRC5D-Targeted CAR T Cells for Myeloma. Mailankody, S., Devlin, SM., Landa, J., et al.[2023]

A new CAR T-cell therapy targeting the GPRC5D protein in patients with refractory or relapsed multiple myeloma has shown promising results, with all 10 treated patients responding positively.

This approach appears to be both safe and effective, providing a potential solution for patients who have developed resistance to existing BCMA-targeting CAR T-cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GPRC5D-Directed CAR Yields 100% Response Rate. [2022]

GPRC5D is a promising new target for CAR T cell therapy in multiple myeloma, as it is expressed on malignant cells and can effectively eliminate these cells even in cases where BCMA is not present.

CAR T cells targeting GPRC5D demonstrated comparable efficacy to BCMA-targeted therapies without causing toxicity, such as hair loss, suggesting a safe and effective alternative for patients who have relapsed after BCMA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Smith, EL., Harrington, K., Staehr, M., et al.[2021]

In a phase 1 study involving 232 patients with heavily pretreated relapsed or refractory multiple myeloma, talquetamab showed a substantial response rate of 70% and 64% for two recommended subcutaneous doses, indicating its efficacy in this challenging patient population.

Common side effects included cytokine release syndrome, skin-related events, and dysgeusia, but these were mostly low-grade, suggesting that talquetamab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. Chari, A., Minnema, MC., Berdeja, JG., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase Ⅱ Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

GPRC5D-Targeted CAR T Cells for Myeloma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

GPRC5D-Directed CAR Yields 100% Response Rate. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. [2022]