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.
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.
12345What 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.
12346Is 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.
12357Eligibility 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.
+10 more
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.
+13 more
Participant Groups
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.
5Treatment groups
Experimental Treatment
Group I: Dose Level 2Experimental Treatment2 Interventions
MCARH125 dose 150 million total CAR+ cells MCARH109 dose 150 million total CAR+ cells
Group II: Dose Level 1Experimental Treatment2 Interventions
MCARH125 dose 150 million total CAR+ cells MCARH109 dose 50 million total CAR+ cells
Group III: Dose Level 0Experimental Treatment2 Interventions
MCARH125 dose 150 million total CAR+ cells MCARH109 dose 0 total CAR+ cells
Group IV: Dose Level -1BExperimental Treatment2 Interventions
MCARH125 dose 50 million total CAR+ cells MCARH109 dose 50 million total CAR+ cells
Group V: Dose Level -1AExperimental Treatment2 Interventions
MCARH125 dose 50 million CAR+ cells MCARH109 dose 0 total CAR+ cells
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Nassau (Limited protocol activities)Uniondale, NY
Memorial Sloan Kettering Cancer CenterNew York, NY
Memorial Sloan Kettering Monmouth (Limited protocol activities)Middletown, NJ
Memorial Sloan Kettering Bergen (Limited protocol activities)Montvale, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
GPRC5D-Targeted CAR T Cells for Myeloma. [2023]B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies have generated responses in patients with advanced myeloma, but relapses are common. G protein-coupled receptor, class C, group 5, member D (GPRC5D) has been identified as an immunotherapeutic target in multiple myeloma. Preclinical studies have shown the efficacy of GPRC5D-targeted CAR T cells, including activity in a BCMA antigen escape model.
GPRC5D-Directed CAR Yields 100% Response Rate. [2022]Patients with refractory or relapsed multiple myeloma usually develop resistance to the two approved BCMA-targeting chimeric antigen receptor (CAR) T cells. A preliminary study of a new CAR T-cell therapy that zeroes in on the GPRC5D protein on multiple myeloma cells suggests that this approach is safe and effective. All 10 patients treated with the GPRC5D-targeting cells showed responses.
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]G protein-coupled receptor, class C group 5 member D (GPRC5D) is considered to be a promising surface target for multiple myeloma (MM) immunotherapy. Here, we report the efficacy and safety of anti-GPRC5D chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory (R/R) MM.
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]Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) has shown activity in treating relapsed or refractory multiple myeloma; however, relapse is still common, and new targets are needed. We aimed to assess the activity and safety profile of G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma.
Anti-GPRC5D/CD3 Bispecific T-Cell-Redirecting Antibody for the Treatment of Multiple Myeloma. [2020]Although treatment advances over recent decades have significantly improved survival of patients with multiple myeloma, there is still an unmet medical need for more effective treatments. In this study, we identified G-protein-coupled receptor family C group 5 member D (GPRC5D) expression on the surface of malignant cells involved in multiple myeloma, but except for plasma cells and B cells, not at appreciable levels on normal hematopoietic cells and bone marrow progenitors, including hematopoietic stem cells. In addition, we constructed IgG-based anti-GPRC5D/CD3 bispecific T-cell-redirecting antibodies (GPRC5D TRAB), which suppressed the tumor growth of GPRC5D-positive myeloma cells through the activation of T cells in vitro and in vivo in xenograft models. Collectively, these findings suggest that GPRC5D is an antigen specific to multiple myeloma and a potential target of TRAB therapy.
GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. [2021]Early clinical results of chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) for multiple myeloma (MM) appear promising, but relapses associated with residual low-to-negative BCMA-expressing MM cells have been reported, necessitating identification of additional targets. The orphan G protein-coupled receptor, class C group 5 member D (GPRC5D), normally expressed only in the hair follicle, was previously identified as expressed by mRNA in marrow aspirates from patients with MM, but confirmation of protein expression remained elusive. Using quantitative immunofluorescence, we determined that GPRC5D protein is expressed on CD138+ MM cells from primary marrow samples with a distribution that was similar to, but independent of, BCMA. Panning a human B cell-derived phage display library identified seven GPRC5D-specific single-chain variable fragments (scFvs). Incorporation of these into multiple CAR formats yielded 42 different constructs, which were screened for antigen-specific and antigen-independent (tonic) signaling using a Nur77-based reporter system. Nur77 reporter screen results were confirmed in vivo using a marrow-tropic MM xenograft in mice. CAR T cells incorporating GPRC5D-targeted scFv clone 109 eradicated MM and enabled long-term survival, including in a BCMA antigen escape model. GPRC5D(109) is specific for GPRC5D and resulted in MM cell line and primary MM cytotoxicity, cytokine release, and in vivo activity comparable to anti-BCMA CAR T cells. Murine and cynomolgus cross-reactive CAR T cells did not cause alopecia or other signs of GPRC5D-mediated toxicity in these species. Thus, GPRC5D(109) CAR T cell therapy shows potential for the treatment of advanced MM irrespective of previous BCMA-targeted therapy.
A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. [2021]T-cell-mediated approaches have shown promise in myeloma treatment. However, there are currently a limited number of specific myeloma antigens that can be targeted, and multiple myeloma (MM) remains an incurable disease. G-protein-coupled receptor class 5 member D (GPRC5D) is expressed in MM and smoldering MM patient plasma cells. Here, we demonstrate that GPRC5D protein is present on the surface of MM cells and describe JNJ-64407564, a GPRC5DxCD3 bispecific antibody that recruits CD3+ T cells to GPRC5D+ MM cells and induces killing of GPRC5D+ cells. In vitro, JNJ-64407564 induced specific cytotoxicity of GPRC5D+ cells with concomitant T-cell activation and also killed plasma cells in MM patient samples ex vivo. JNJ-64407564 can recruit T cells and induce tumor regression in GPRC5D+ MM murine models, which coincide with T-cell infiltration at the tumor site. This antibody is also able to induce cytotoxicity of patient primary MM cells from bone marrow, which is the natural site of this disease. GPRC5D is a promising surface antigen for MM immunotherapy, and JNJ-64407564 is currently being evaluated in a phase 1 clinical trial in patients with relapsed or refractory MM (NCT03399799).