CAR-T Cell Therapy for Multiple Myeloma

(MM Trial)

Recruiting at 18 trial locations

Overseen By Angie Schinkel

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

275 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new CAR-T cell therapy called P-BCMA-ALLO1 for individuals with multiple myeloma, a type of blood cancer that has returned or did not respond to previous treatments. The study explores different methods of administering the therapy to determine the most effective approach. It targets those who have tried treatments such as proteasome inhibitors, immunomodulatory drugs, and anti-CD38 therapy but continue to face challenges with their condition. Participants must have been diagnosed with active multiple myeloma and have not found success with these treatments. As a Phase 1 trial, this research focuses on understanding the treatment's effects 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 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.

Is there any evidence suggesting that P-BCMA-ALLO1 CAR-T cells are likely to be safe for humans?

Research has shown that P-BCMA-ALLO1 CAR-T cells have been safe so far. Studies have primarily focused on side effects that might limit the dose, and the results have been promising. This treatment is in an early stage, so researchers are working to find the safest dose.

While specific details about side effects aren't provided, this phase aims to identify potential side effects and assess their severity. This treatment is being tested in individuals who have already tried other treatments for multiple myeloma, making their experiences crucial.

For more questions or to determine if you might be a suitable candidate, consider contacting the research team involved in the trial. They can provide information specific to your situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about P-BCMA-ALLO1 CAR-T cells for multiple myeloma because this treatment uses a groundbreaking approach. Unlike traditional therapies such as chemotherapy, this treatment harnesses the power of genetically engineered T cells to target and kill cancer cells. The CAR-T cells are specifically designed to recognize and attack cells expressing BCMA, a protein commonly found on multiple myeloma cells. This targeted mechanism allows for a more precise attack on cancer cells, potentially leading to better outcomes and fewer side effects compared to conventional treatments.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that P-BCMA-ALLO1 CAR-T cells yield promising results for treating relapsed or hard-to-treat multiple myeloma. This trial evaluates the effectiveness of P-BCMA-ALLO1 CAR-T cells across various treatment arms, each involving different conditioning chemotherapy regimens. This treatment demonstrates a high overall response rate, with many patients responding well. It is particularly effective for those who have already tried several other treatments. The safety profile of P-BCMA-ALLO1 is favorable, indicating it might be well-tolerated by patients. This therapy targets BCMA, a protein on myeloma cells, using modified immune cells to attack the cancer. Early evidence supports its potential as a strong option for those with difficult-to-treat multiple myeloma. ^{2 6 7 8 9}

Who Is on the Research Team?

Maika Onishi, M.D.

Principal Investigator

Senior Medical Director

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• P-BCMA-ALLO1 CAR-T cells

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.

How Is the Trial Designed?

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 MP1.5) Experimental Treatment 3 Interventions

Single weight based IV administration of P-BCMA-ALLO1 and methotrexate following conditioning chemotherapy regimen MP1.5 Rimiducid may be administered as indicated

Group XIV: 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 XV: 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 XVI: 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 XVII: 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 XVIII: 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.

P-BCMA-ALLO1 CAR-T cells is already approved in United States for the following indications:

Approved in United States as P-BCMA-ALLO1 for:

• Relapsed/Refractory Multiple Myeloma

Who Is Running the Clinical Trial?

Poseida Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

780+

Roche-Genentech

Industry Sponsor

Trials

27

Recruited

3,800+

Published Research Related to This Trial

In a phase II trial involving 69 patients with relapsed or refractory multiple myeloma, the combination of anti-BCMA and anti-CD19 CAR T cells resulted in a high overall response rate of 92%, with 60% achieving a complete response.

The treatment demonstrated a median progression-free survival of 18.3 months and a manageable safety profile, although 95% of patients experienced cytokine release syndrome, indicating the need for monitoring during treatment.

NCBI (Pubmed)

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. Wang, Y., Cao, J., Gu, W., et al.[2022]

The newly developed BCMA-targeted fourth-generation CAR-T cells (BCMA-7 × 19 CAR-T cells) showed enhanced capabilities in expanding, differentiating, migrating, and killing cancer cells compared to previous CAR-T therapies, indicating improved efficacy against refractory/relapsed multiple myeloma (R/R MM).

In a first-in-human clinical trial involving two patients, BCMA-7 × 19 CAR-T cells demonstrated promising safety and efficacy, with one patient achieving complete remission (CR) and the other a very good partial response (VGPR) after just one dose, and only mild cytokine release syndrome observed.

NCBI (Pubmed)

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. Duan, D., Wang, K., Wei, C., et al.[2021]

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]

BCMA-CAR-T cells, engineered to target the B-cell maturation antigen (BCMA), demonstrated strong cytotoxic effects against BCMA-positive myeloma cells in vitro, significantly reducing the number of residual cancer cells compared to control groups.

In a mouse model of multiple myeloma, treatment with BCMA-CAR-T cells significantly increased survival time, indicating their potential as an effective therapy for patients with BCMA-positive multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Targeting BCMA in multiple myeloma using chimeric antigen receptor-engineered T cells]. Zhong, MJ., Xu, YX., Xing, HY., et al.[2020]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4828/533291/A-Phase-1-Study-of-P-BCMA-ALLO1-a-Non-Viral

A Phase 1 Study of P-BCMA-ALLO1, a Non-Viral, Allogeneic ... P-BCMA-ALLO1 demonstrates a promising ORR and favorable safety profile when administered with optimized LD. It is highly active, regardless of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04960579

NCT04960579 | P-BCMA-ALLO1 Allogeneic CAR-T Cells ... Phase 1 study comprised of open-label, dose escalation, multiple cohorts of P-BCMA-ALLO1 allogeneic T stem cell memory (Tscm) CAR-T cells in subjects with ...

3. poseida.com poseida.com/wp-content/uploads/2024/04/AACR_Dholaria_CT071_04052024_FINAL.pdf

Clinical Activity of P-BCMA-ALLO1, a B-cell ... Here we report the safety and early efficacy results for the 5 patients who were treated with P-BCMA-ALLO1 after having progressed on BCMA targeting CAR-T, TCE ...

4. onclive.com onclive.com/view/off-the-shelf-car-t-cell-therapy-p-bcma-allo1-is-efficacious-in-relapsed-refractory-multiple-myeloma

Off-the-Shelf CAR T-Cell Therapy P-BCMA-ALLO1 Is ... P-BCMA-ALLO1 displayed high response rates and compelling safety in a heavily pretreated population of patients with relapsed/refractory multiple myeloma.

5. multiplemyelomahub.com multiplemyelomahub.com/medical-information/phase-i-trial-on-the-efficacy-and-safety-of-p-bcma-allo1-car-t-cell-therapy-in-rrmm

Phase I trial on the efficacy and safety of P-BCMA-ALLO1 ... We summarize interim results from a phase I trial of P-BCMA-ALLO1, an allogeneic BCMA-directed CAR T-cell therapy, in patients with relapsed/refractory multiple

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3479/503645/Early-Safety-Results-of-P-BCMA-ALLO1-a-Fully

Early Safety Results of P-BCMA-ALLO1, a Fully Allogeneic ... The primary objective is to assess the safety and maximum tolerated dose (MTD) of P-BCMA-ALLO1 based on dose limiting toxicity (DLT) in RRMM ...

7. prnewswire.com prnewswire.com/news-releases/poseida-therapeutics-reports-positive-interim-phase-1-results-for-allogeneic-car-t-therapy-p-bcma-allo1-with-high-overall-response-rates-in-heavily-pretreated-relapsedrefractory-multiple-myeloma-patients-302261471.html

Poseida Therapeutics Reports Positive Interim Phase 1 ... Data showed a 91% ORR with P-BCMA-ALLO1 in an optimized lymphodepletion arm, including a 100% ORR in BCMA-naïve patients, and an 86% ORR in those who had ...

8. astctjournal.org astctjournal.org/article/S2666-6367(25)00073-9/fulltext

A Phase 1 Study of P-BCMA-ALLO1, a Non-Viral ... P-BCMA-ALLO1 demonstrates a promising ORR and favorable safety profile, regardless of prior exposure to BCMA-targeted therapy. The P-BCMA-ALLO1-001 (NCT04960579) ...

9. targetedonc.com targetedonc.com/view/off-the-shelf-car-t-therapy-p-bcma-allo1-shows-strong-activity-in-r-r-myeloma

Off-the-Shelf CAR-T Therapy P-BCMA-ALLO1 Shows ... The overall response rate to P-BCMA-ALLO1 was 88% among 32 patients, including 100% in patients who had no prior BCMA-targeted therapy and 75% ...