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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called OriCAR-017, a chimeric antigen receptor (CAR)-T cell therapy targeting G protein-coupled receptor class-C group-5 member-D (GPRC5D), for individuals with multiple myeloma, a type of blood cancer that has returned or is not responding to other treatments. The main goal is to assess the treatment's safety and effectiveness. The trial seeks participants who have undergone multiple myeloma treatments but still face the disease. Participants must have experienced a return of cancer or a lack of response to their last treatment. As a Phase 1 trial, this research focuses on understanding how OriCAR-017 works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that OriCAR-017 is likely to be safe for humans?

Research shows that a new treatment called GPRC5D-targeted CAR T-cell therapy, such as OriCAR-017, is under investigation for multiple myeloma, a type of blood cancer. In patients whose cancer has returned or hasn't responded to other treatments, this therapy has shown promise, indicating its potential usefulness and warranting further testing.

While detailed safety information is not yet available, the ongoing studies suggest that the treatment is generally well-tolerated. OriCAR-017 is currently in a Phase 1 trial, marking its first test in humans to assess safety and identify any side effects.

More research is needed to fully understand its safety, but the continued interest in studying this treatment is encouraging. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, such as chemotherapy or proteasome inhibitors, OriCAR-017 is a CAR-T cell therapy, which means it uses specially modified immune cells to target and destroy cancer cells. Researchers are excited about OriCAR-017 because it offers a more personalized approach, harnessing the patient’s own immune system to combat the disease. This approach has the potential to deliver more precise and potent results, with the possibility of long-lasting remission.

What evidence suggests that OriCAR-017 might be an effective treatment for multiple myeloma?

Research has shown that OriCAR-017, a type of CAR T-cell therapy, holds promise for treating multiple myeloma that has returned or resisted other treatments. Studies have found that this therapy produces positive results in patients. It targets a specific part of the cancer called GPRC5D, which plays a crucial role in multiple myeloma, enhancing the treatment's effectiveness. OriCAR-017 is also considered safe and helps maintain the treatment's effectiveness in the body for a longer duration. This makes it a hopeful option for those facing this challenging form of cancer. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/ashclinicalnews/news/7958/Phase-I-Study-Shows-Long-Term-Efficacy-of-GPRC5D

Phase I Study Shows Long-Term Efficacy of GPRC5D ... GPRC5D showed favorable treatment responses in all patients with relapsed or refractory (R/R) multiple myeloma (MM) in the long-term follow-up of the phase I ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2209900

GPRC5D-Targeted CAR T Cells for Myeloma The results of this study of a GPRC5D-targeted CAR T-cell therapy (MCARH109) confirm that GPRC5D is an active immunotherapeutic target in multiple myeloma.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36170501/

GPRC5D-Targeted CAR T Cells for Myeloma - PubMed The results of this study of a GPRC5D-targeted CAR T-cell therapy (MCARH109) confirm that GPRC5D is an active immunotherapeutic target in ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302622003726

Articles GPRC5D CAR T cells (OriCAR-017) in patients ... Our results showed a good safety profile and preliminary activity of GPRC5D-targeted CAR T-cell therapy for patients with relapsed or refractory multiple ...

5. multiplemyelomahub.com multiplemyelomahub.com/medical-information/efficacy-of-oricar-017-a-gprc5d-directed-car-t-cell-therapy-in-patients-with-rr-mm-findings-from-the-polaris-study

Efficacy of OriCAR-017, a GPRC5D-directed CAR T-cell ... OriCAR-017 is a second-generation, autologous, GPRC5D-directed CAR T-cell therapy that improves the expansion and durability of CAR T-cells post-transfusion.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36725117/

GPRC5D CAR T cells (OriCAR-017) in patients with ... GPRC5D-targeted CAR T-cell therapy is a promising treatment modality for patients with relapsed or refractory multiple myeloma and deserves further testing.

7. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(22)00372-6/abstract

GPRC5D CAR T cells (OriCAR-017) in patients with ... The results of this study suggest that GPRC5D is an active target for immunotherapy in multiple myeloma. GPRC5D-targeted CAR T-cell therapy is a promising ...

8. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1466443/full

Efficacy and safety of chimeric antigen receptor T cells ... The results confirmed that GPRC5D is an effective immunotherapeutic target for CAR-T therapy in RRMM. Although both BCMA CAR-T and GPRC5D CAR-T ...