MCARH109 + MCARH125 for Multiple Myeloma

Recruiting at 6 trial locations

Overseen By Saad Usmani, MD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Proteasome inhibitors, Immunomodulatory drugs, CD38 antibodies

Must not be taking: Systemic steroids

Disqualifiers: Pregnancy, HIV, Hepatitis B/C, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Variable, based on dose escalation

15 Participants Needed

Trial Summary

What is the purpose of this trial?

A sample of participants' T cells will be sent to a laboratory, where the cells will be made into the study therapy, MCARH109 and MCARH125. Participants will receive either MCARH125 alone or MCARH125 with MCARH109.

Do I need to stop my current medications to join the trial?

The trial requires a 14-day washout period from myeloma therapies and radiation before starting the study. For experimental treatments, the washout is 5 half-lives or 14 days, whichever is shorter. The protocol does not specify other medications, so consult your doctor for guidance.

Will I have to stop taking my current medications?

The trial requires a 14-day period without myeloma therapies before certain procedures, so you may need to stop some medications. However, the protocol does not specify all medications, so it's best to discuss your specific situation with the trial team.

What data supports the idea that MCARH109 + MCARH125 for Multiple Myeloma is an effective treatment?

The available research shows that MCARH109 + MCARH125, which targets a specific protein called GPRC5D on multiple myeloma cells, is effective. One study reported a 100% response rate in 10 patients with relapsed or resistant multiple myeloma, meaning all patients showed improvement. This is significant because other treatments targeting a different protein, BCMA, often lead to relapses. Therefore, MCARH109 + MCARH125 appears to be a promising alternative for patients who do not respond to existing treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment MCARH109 + MCARH125 for Multiple Myeloma?

Research shows that targeting the GPRC5D protein on multiple myeloma cells with CAR T-cell therapy is promising, with studies reporting a 100% response rate in some patients. This suggests that the treatment could be effective for patients with relapsed or resistant multiple myeloma. ^{1 2 3 4 5}

What safety data is available for GPRC5D-targeted CAR T-cell therapy in multiple myeloma?

The safety data for GPRC5D-targeted CAR T-cell therapy in multiple myeloma indicates that this approach is generally safe and effective. Studies have shown promising results, with a 100% response rate in a preliminary study involving 10 patients. Early clinical trials, such as the POLARIS phase 1 trial, have assessed the safety profile of GPRC5D-targeted CAR T cells, showing activity in relapsed or refractory multiple myeloma. Preclinical studies also demonstrated that GPRC5D-targeted CAR T cells did not cause significant toxicity, such as alopecia, in animal models. Overall, the therapy shows potential for treating advanced multiple myeloma, even in cases where BCMA-targeted therapies have failed. ^{1 2 3 4 6}

Is the GPRC5D-targeted CAR T-cell therapy safe for humans?

Preliminary studies suggest that GPRC5D-targeted CAR T-cell therapy is generally safe, with no significant toxicity observed in early trials for multiple myeloma. ^{1 2 3 4 6}

Is the treatment MCARH109, MCARH125 a promising treatment for multiple myeloma?

Yes, the treatment MCARH109, MCARH125 is promising for multiple myeloma. It targets a protein called GPRC5D on cancer cells, which has shown to be effective in patients who have not responded to other treatments. In studies, all patients treated with this therapy showed positive responses, indicating its potential as a new option for those with difficult-to-treat multiple myeloma. ^{1 2 3 5 7}

How is the treatment MCARH109 + MCARH125 for multiple myeloma different from other treatments?

This treatment is unique because it targets the GPRC5D protein on multiple myeloma cells, which is different from the more common BCMA-targeting therapies. It uses CAR T-cell therapy, which involves modifying a patient's own immune cells to better recognize and attack cancer cells, offering a new option for patients who have relapsed or are resistant to existing treatments. ^{1 2 3 5 7}

Research Team

Sham Mailankody, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with multiple myeloma that's come back or hasn't responded to treatment, including a proteasome inhibitor, an immunomodulatory drug, and a CD38 antibody. They should have had at least three prior treatments and be in good physical condition. Pregnant women or those with certain heart conditions, active infections like HIV/Hepatitis B/C, other cancers, or recent steroid use can't join.

Inclusion Criteria

I've had treatments including proteasome inhibitors, immunomodulatory drugs, CD38 antibodies, and high-dose chemo with stem cell support.

My kidney, liver, lung, and heart functions are all within normal ranges.

My blood counts meet the required levels without recent transfusions or growth factor support.

Exclusion Criteria

I have been diagnosed with plasma cell leukemia.

I have another active cancer besides the one being treated.

I haven't had myeloma treatment in the last 6 months, except possibly CAR T cell therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either MCARH125 alone or MCARH125 with MCARH109

Variable, based on dose escalation

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 24 months

Treatment Details

Interventions

• MCARH109
• MCARH125

Trial Overview The study tests two therapies: MCARH125 alone or combined with MCARH109 on participants' T cells modified in the lab to fight cancer. It aims to see how well these new treatments work against relapsed/refractory multiple myeloma.

Participant Groups

Group I: Dose Level 2 Experimental Treatment 2 Interventions

MCARH125 dose 150 million total CAR+ cells MCARH109 dose 150 million total CAR+ cells

Group II: Dose Level 1 Experimental Treatment 2 Interventions

MCARH125 dose 150 million total CAR+ cells MCARH109 dose 50 million total CAR+ cells

Group III: Dose Level 0 Experimental Treatment 2 Interventions

MCARH125 dose 150 million total CAR+ cells MCARH109 dose 0 total CAR+ cells

Group IV: Dose Level -1B Experimental Treatment 2 Interventions

MCARH125 dose 50 million total CAR+ cells MCARH109 dose 50 million total CAR+ cells

Group V: Dose Level -1A Experimental Treatment 2 Interventions

MCARH125 dose 50 million CAR+ cells MCARH109 dose 0 total CAR+ cells

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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]

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]

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]

GPRC5D is specifically expressed on malignant cells in multiple myeloma, making it a promising target for new treatments, as it is not significantly present on normal blood cells or stem cells.

The study developed bispecific T-cell-redirecting antibodies (GPRC5D TRAB) that effectively suppressed tumor growth in GPRC5D-positive myeloma cells by activating T cells, showing potential for effective therapy in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GPRC5D/CD3 Bispecific T-Cell-Redirecting Antibody for the Treatment of Multiple Myeloma. Kodama, T., Kochi, Y., Nakai, W., et al.[2020]

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]

The bispecific antibody JNJ-64407564 targets the GPRC5D antigen on multiple myeloma (MM) cells, effectively recruiting T cells to kill these cancer cells, demonstrating specific cytotoxicity in both laboratory and patient samples.

JNJ-64407564 has shown promising results in preclinical models, inducing tumor regression and T-cell infiltration in GPRC5D+ MM murine models, and is currently being tested in a phase 1 clinical trial for patients with relapsed or refractory MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Pillarisetti, K., Edavettal, S., Mendonça, M., et al.[2021]

References

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

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

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

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

3. 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]

4. 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]

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

Anti-GPRC5D/CD3 Bispecific T-Cell-Redirecting Antibody for the Treatment of Multiple Myeloma. [2020]

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

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

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

A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. [2021]