CAR T-Cell Therapy for Multiple Myeloma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MCARH109, a GPRC5D-targeted CAR T-cell therapy, to determine its safety and effectiveness in stopping the growth of multiple myeloma, a type of blood cancer. Researchers aim to find the safest dose and assess any positive or negative effects. Individuals whose multiple myeloma did not respond to at least three different treatments might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that MCARH109 is likely to be safe for humans?

Research has shown that MCARH109, a new CAR T-cell therapy, is being tested for safety in treating multiple myeloma, a type of blood cancer. In earlier studies, 71% of patients responded positively to MCARH109, despite receiving different treatment doses. This suggests the treatment could benefit many patients.

As this is an early-stage trial, the main goal is to find the safest dose and identify any side effects. While detailed safety information isn't available yet, early trials like this one are designed to carefully test new treatments to understand any risks.

Participants might experience side effects, which is common with many treatments, especially new ones. However, the trial will closely monitor these effects to ensure participant safety. Those considering participation should discuss any concerns with the trial team and inquire about the safety measures in place. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about MCARH109 CAR T-Cell Therapy for multiple myeloma because it represents a novel approach that modifies a patient's own T cells to specifically target cancer cells. Unlike standard treatments like chemotherapy or immunomodulatory drugs, this therapy uses a lentiviral vector to genetically alter T cells to recognize and attack cells expressing the GPRC5D protein, which is often found on multiple myeloma cells. This precision targeting has the potential to offer more effective and longer-lasting results with fewer side effects. Additionally, the process of expanding these modified T cells ensures that a powerful army of cancer-fighting cells is ready to be deployed, potentially leading to quicker and more robust responses.

What evidence suggests that MCARH109 might be an effective treatment for multiple myeloma?

Research has shown that MCARH109, a new therapy targeting the protein GPRC5D, may help treat multiple myeloma, a type of cancer. In studies, 71% of patients responded to this treatment, with the response lasting for a median duration. Specifically, one study found that 94.1% of patients showed improvement, and more than half had no detectable cancer after treatment. These early findings suggest that targeting GPRC5D could effectively combat this cancer. However, further research is needed to confirm these results and understand the treatment's long-term safety and effectiveness. ^{1 2 3 5 6}

Who Is on the Research Team?

Sham Mailankody, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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]

Citations

1. 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 multiple myeloma.

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. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-24-01785

Phase I Trial of MCARH109, a G Protein–Coupled ... The median overall survival (OS) was NR and the 3-year OS estimate was 59% (95% CI, 40 to 88). Possible GPRC5D loss via immunohistochemistry was ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3451/529721/GPRC5D-Targeted-CAR-T-Cell-Therapy-CT071-for-the

GPRC5D-Targeted CAR T-Cell Therapy CT071 for the ... The overall response rate (ORR) was 94.1% (16/17), and the stringent complete response (sCR) rate was 52.9% (9/17). Notably, 7 patients achieved ...

5. multiplemyelomahub.com multiplemyelomahub.com/medical-information/safety-and-efficacy-of-the-gprc5d-targeted-car-t-cell-therapy-mcarh109

Safety and efficacy of the GPRC5D-targeted CAR T-cell ... A total of 71% (95% confidence interval (CI), 44–90) of patients showed a response across all dose levels of MCARH109, with a median duration of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39631041/

Phase I Trial of MCARH109, a G Protein-Coupled Receptor ... The median overall survival (OS) was NR and the 3-year OS estimate was 59% (95% CI, 40 to 88). Possible GPRC5D loss via immunohistochemistry was ...