CAR-T Cell Therapy for Multiple Myeloma

(MM Trial)

Recruiting at16 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Poseida Therapeutics, Inc.

Must be taking: Proteasome inhibitors, IMiDs, Anti-CD38

Must not be taking: Immunosuppressives, Corticosteroids, Monoclonal antibodies

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests a new therapy using modified donor immune cells to treat patients with a difficult-to-treat type of blood cancer. The therapy aims to use these engineered cells to find and destroy the cancer cells. CAR-T cell therapy has become a new and highly effective treatment option, especially for patients with challenging blood cell cancers.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. You must not have received anti-cancer medications within 2 weeks, monoclonal antibody therapy within 4 weeks, immunosuppressive medications within 2 weeks, or systemic corticosteroid therapy within 1 week before starting the study treatment.

What data supports the effectiveness of the treatment P-BCMA-ALLO1 CAR-T cells for multiple myeloma?

Research shows that CAR-T cells targeting BCMA (a protein found on myeloma cells) can effectively kill myeloma cells and improve survival in animal models. Clinical trials have demonstrated high response rates in patients with relapsed or hard-to-treat multiple myeloma, with some patients achieving complete remission. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for treating multiple myeloma?

CAR-T cell therapy targeting BCMA has shown a manageable safety profile in multiple studies for treating multiple myeloma. Common side effects include mild to moderate cytokine release syndrome (a reaction that can cause fever and flu-like symptoms), but severe cases are rare and reversible. No severe neurotoxicity or dose-limiting toxicities were observed in the trials. ^{1 2 3 6 7}

How is the treatment P-BCMA-ALLO1 CAR-T cells different from other treatments for multiple myeloma?

P-BCMA-ALLO1 CAR-T cells are a unique treatment for multiple myeloma because they use genetically modified T cells to specifically target and destroy cancer cells expressing the BCMA protein, which is not found on normal essential cells. This approach is different from traditional treatments as it offers a targeted mechanism of action, potentially leading to better outcomes for patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Research Team

Rajesh Belani, M.D.

Principal Investigator

Vice President, Clinical Development

Eligibility Criteria

Adults with active Multiple Myeloma who've had prior treatments including proteasome inhibitors, IMiDs, and anti-CD38 therapy. They must have measurable disease that's relapsed/refractory, be willing to use birth control, and have good organ function. Excluded are pregnant individuals, those with certain viral infections or a history of severe allergies to trial drugs.

Inclusion Criteria

I have recovered from side effects of previous treatments.

I am fully active or restricted in physically strenuous activity but can do light work.

Women who could become pregnant must have a negative pregnancy test before starting the treatment.

Exclusion Criteria

I received monoclonal antibody therapy less than 4 weeks ago.

My cancer has spread to my brain or spinal cord.

You have a current autoimmune disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Therapy

Participants may receive a lymphodepletion therapy regimen before administration of allogeneic CAR-T cells

1-2 weeks

Treatment

Administration of P-BCMA-ALLO1 CAR-T cells, either as a single or multiple dose(s), following conditioning chemotherapy

4 weeks

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety, tolerability, and response, including assessment of dose limiting toxicities and adverse events

36 months

Regular visits for safety and efficacy assessments

Long-term Follow-up

Extended monitoring for anti-myeloma effects and overall survival

15 years

Treatment Details

Interventions

• P-BCMA-ALLO1 CAR-T cells (CAR T-cell Therapy)

Trial Overview The study is testing P-BCMA-ALLO1 CAR-T cells alongside Rimiducid in adults with Multiple Myeloma that has not responded to standard treatments. It's an early-phase trial where researchers will test different doses to find the safest and most effective one.

Participant Groups

Group I: P-BCMA-ALLO1 CAR-T cells (Arm480) Experimental Treatment 2 Interventions

Single fixed dose IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S, P1, P1.5 or P2. Rimiducid may be administered as indicated.

Group II: P-BCMA-ALLO1 CAR-T cells (Arm160) Experimental Treatment 2 Interventions

Single fixed dose IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S, P1, P1.5 or P2. Rimiducid may be administered as indicated.

Group III: P-BCMA-ALLO1 CAR-T cells (Arm S) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S. Rimiducid may be administered as indicated.

Group IV: P-BCMA-ALLO1 CAR-T cells (Arm RS) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RS. Rimiducid may be administered as indicated.

Group V: P-BCMA-ALLO1 CAR-T cells (Arm RP2) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP2. Rimiducid may be administered as indicated.

Group VI: P-BCMA-ALLO1 CAR-T cells (Arm RP1.5) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP1.5. Rimiducid may be administered as indicated.

Group VII: P-BCMA-ALLO1 CAR-T cells (Arm RP1) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP1. Rimiducid may be administered as indicated.

Group VIII: P-BCMA-ALLO1 CAR-T cells (Arm R) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen R. Rimiducid may be administered as indicated.

Group IX: P-BCMA-ALLO1 CAR-T cells (Arm P2) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P2. Rimiducid may be administered as indicated.

Group X: P-BCMA-ALLO1 CAR-T cells (Arm P1.5) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P1.5. Rimiducid may be administered as indicated.

Group XI: P-BCMA-ALLO1 CAR-T cells (Arm P1) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P1. Rimiducid may be administered as indicated.

Group XII: P-BCMA-ALLO1 CAR-T cells (Arm N) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1. Rimiducid may be administered as indicated.

Group XIII: P-BCMA-ALLO1 CAR-T cells (Arm F) Experimental Treatment 2 Interventions

Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen F. Rimiducid may be administered as indicated.

Group XIV: P-BCMA-ALLO1 CAR-T cells (Arm CP2) Experimental Treatment 2 Interventions

Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP2. Rimiducid may be administered as indicated.

Group XV: P-BCMA-ALLO1 CAR-T cells (Arm CP1.5) Experimental Treatment 2 Interventions

Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP1.5. Rimiducid may be administered as indicated.

Group XVI: P-BCMA-ALLO1 CAR-T cells (Arm CP1) Experimental Treatment 2 Interventions

Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP1. Rimiducid may be administered as indicated.

Group XVII: P-BCMA-ALLO1 CAR-T cells (Arm C) Experimental Treatment 2 Interventions

Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen C. Rimiducid may be administered as indicated.

Who Is Running the Clinical Trial?

Poseida Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

780+

Roche-Genentech

Industry Sponsor

Trials

27

Recruited

3,800+

Findings from Research

In a first-in-humans clinical trial involving 16 patients with heavily treated multiple myeloma, CAR-BCMA T cells demonstrated an impressive overall response rate of 81%, with 63% achieving very good partial or complete responses.

The treatment was associated with significant anti-myeloma activity, including eradication of bone marrow myeloma and resolution of soft-tissue plasmacytomas, although some patients experienced severe but reversible cytokine-release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. Brudno, JN., Maric, I., Hartman, SD., et al.[2019]

B-cell maturation antigen (BCMA) CAR T cells are emerging as a highly effective treatment for multiple myeloma, showing promise for inclusion in first-line therapy based on clinical and preclinical data.

Advancements in patient stratification through genomic analysis and improvements in CAR T-cell manufacturing are enhancing early diagnosis, management of side effects, and overall access to this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? Rasche, L., Hudecek, M., Einsele, H.[2023]

HBI0101, a novel anti-BCMA CAR T-cell therapy, demonstrated a high overall response rate of 75% in a phase I study involving 20 heavily pre-treated patients with relapsed/refractory multiple myeloma, with a dose-dependent increase in efficacy observed in higher doses.

The therapy showed a manageable safety profile, with 90% of patients experiencing only mild cytokine release syndrome and no severe toxicities, indicating that HBI0101 could be a safe and effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. Asherie, N., Kfir-Erenfeld, S., Avni, B., et al.[2023]

KITE-585, an autologous CAR T-cell therapy targeting BCMA, showed a manageable safety profile in a phase 1 study with 14 patients, where no dose-limiting toxicities were observed and all patients experienced at least one grade ≥ 3 treatment-emergent adverse event.

Despite the safety, KITE-585 demonstrated limited efficacy, with only one patient achieving a partial response and low levels of CAR T-cell expansion and associated cytokines, indicating minimal anti-tumor activity in relapsed/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, multicenter study evaluating the safety and efficacy of KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma. Cornell, RF., Bishop, MR., Kumar, S., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The BCMA-Targeted Fourth-Generation CAR-T Cells Secreting IL-7 and CCL19 for Therapy of Refractory/Recurrent Multiple Myeloma. [2021]

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

T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. [2019]

3. China pubmed.ncbi.nlm.nih.gov

[Targeting BCMA in multiple myeloma using chimeric antigen receptor-engineered T cells]. [2020]

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

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? [2023]

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

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. [2023]

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

A phase 1, multicenter study evaluating the safety and efficacy of KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma. [2022]