CAR T-Cell Therapy for Multiple Myeloma

Recruiting at 6 trial locations

Overseen By Urvi A Shah, MD

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

17 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will test the safety of the study treatment, MCARH109, at different doses, to see which dose is safest in people, and to look for any good and bad effects of this treatment. The study treatment could stop the growth of the cancer, but it could also cause side effects.

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. It's best to discuss your specific medications with the trial team to understand what changes might be necessary.

What data supports the effectiveness of the treatment MCARH109, a GPRC5D-targeted CAR T-cell therapy, for multiple myeloma?

Research shows that GPRC5D-targeted CAR T-cell therapy has been effective in treating patients with relapsed or resistant multiple myeloma, with one study reporting a 100% response rate in 10 patients. This suggests that targeting the GPRC5D protein on myeloma cells can be a promising approach for this condition. ^{1 2 3 4 5}

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

Studies suggest that GPRC5D-targeted CAR T-cell therapy is generally safe for humans, with no significant safety concerns reported in early trials for multiple myeloma. In animal studies, this therapy did not cause hair loss or other signs of toxicity. ^{1 2 3 4 6}

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

MCARH109 is a unique CAR T-cell therapy that targets the GPRC5D protein on multiple myeloma cells, offering a new approach for patients who have relapsed or are resistant to existing BCMA-targeting therapies. This treatment has shown promising results, with all patients in a study responding to the therapy. ^{1 2 3 4 5}

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 monoclonal antibody. They should have had at least three prior treatments and meet specific health criteria like good organ function and blood counts.

Inclusion Criteria

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

I am fully active or can carry out light work.

It has been over 100 days since my stem cell transplant.

Exclusion Criteria

I have been diagnosed with plasma cell leukemia.

I have been on steroids within the last two weeks.

You have an ongoing autoimmune disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and T Cell Modification

Patients undergo leukapheresis for T cell enrichment, activation, and genetic modification using a lentiviral vector encoding a GPRC5D targeted CAR (MCARH109).

2-3 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy prior to T cell infusion.

1 week

T Cell Infusion

Modified T cells are infused 2-7 days following completion of conditioning chemotherapy.

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including bone marrow aspirate and biopsy at approximately 1 and 4 weeks following the T cell infusion.

4 weeks

Long-term Follow-up

Participants are observed for a minimum of 30 days before dose escalation and monitored for up to 1 year to determine the maximum tolerated dose.

1 year

Treatment Details

Interventions

• MCARH109

Trial Overview The study tests different doses of MCARH109 T cells infused into patients to find the safest dose. It aims to determine the effects of this CAR T-cell therapy on stopping cancer growth while monitoring any side effects that may occur during treatment.

Participant Groups

Group I: Targeted MCARH109 CAR Modified T cells Experimental Treatment 1 Intervention

Patients will undergo leukapheresis of peripheral blood for further T cell enrichment; activation and genetic modification using a lentiviral vector encoding a GPRC5D targeted CAR (MCARH109). These T cells will be expanded and after the appropriate number of cells is generated, the modified T cells may be infused fresh or frozen for later use according to standard operation procedures. These modified T cell infusions will be administered 2-7 days following completion of conditioning chemotherapy.

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 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]

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-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 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]

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]

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]

References

1. 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]

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

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

3. 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]

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

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

5. 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]

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]