Allogeneic CAR-T Cell Therapy for B-Cell Cancer

Recruiting at 16 trial locations

Overseen By Angie Schinkel

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Poseida Therapeutics, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called P-CD19CD20-ALLO1, a type of CAR-T cell therapy, for individuals with certain B-cell cancers that have returned or not responded to other treatments. The main goal is to assess the therapy's safety and determine the optimal dose. Individuals with B-cell cancers like diffuse large B-cell lymphoma (DLBCL) who have not succeeded with other treatments might be suitable candidates. Participants must have a confirmed diagnosis and have undergone prior treatments, including chemotherapy targeting specific proteins on cancer cells. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received certain anti-cancer medications, monoclonal antibody therapy, or immunosuppressive medications within specific timeframes before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that P-CD19CD20-ALLO1 is likely to be safe for humans?

Research has shown that allogeneic CAR-T cell therapy, such as P-CD19CD20-ALLO1, is generally safe for patients with B-cell cancers. In studies, patients have tolerated this treatment well, with serious side effects like GVHD (graft-versus-host disease) occurring in fewer than 10% of cases. This indicates that most people do not experience severe reactions.

"Allogeneic" means the therapy uses cells from a donor, not the patient, which can reduce certain risks. The therapy targets specific proteins, CD19 and CD20, on cancer cells to destroy them. Although the trial is in its early stages, it aims to determine the safest dose for future use.

Overall, the treatment's safety record in similar studies suggests it could be a promising option for those with relapsed or difficult-to-treat B-cell cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about P-CD19CD20-ALLO1 CAR-T cells because they represent a potentially groundbreaking approach to treating B-cell cancers. Unlike traditional treatments like chemotherapy, which attack rapidly dividing cells broadly, this therapy is more targeted. It uses engineered T-cells to specifically seek out and destroy cancer cells by recognizing proteins CD19 and CD20 on their surfaces. This precision could lead to more effective treatments with fewer side effects. Additionally, the use of allogeneic (donor-derived) CAR-T cells means these treatments could be more widely accessible and readily available compared to autologous (patient-derived) CAR-T therapies, which require complex customization for each patient.

What evidence suggests that this treatment might be an effective treatment for B-cell cancer?

Research has shown that allogeneic CAR-T therapy, such as P-CD19CD20-ALLO1, holds promise for treating B-cell cancers. Studies have found that this therapy can lead to complete remission (CR) in about 60% of patients with these cancers. In this trial, participants will receive P-CD19CD20-ALLO1, which targets specific markers, CD19 and CD20, on cancer cells, potentially resulting in more effective and long-lasting destruction of these cells. This therapy is also designed as an "off-the-shelf" treatment, which could make it more accessible and quicker to use than personalized treatments. Early results suggest it works well and lasts a long time, especially for B-cell cancers that have returned or are hard to treat. ^{1 2 3 4 6}

Who Is on the Research Team?

Simon Heidegger, MD

Principal Investigator

Lead Medical Director, Oncology, Genentech Research Early Development

Are You a Good Fit for This Trial?

Adults (≥18 years) with certain B cell malignancies like DLBCL, FL, MCL, MZL, PMBCL or CLL that have relapsed or are not responding to treatment. They must have tried specific therapies and meet health criteria including organ function and blood counts. Pregnant individuals, those with autoimmune diseases or active infections are excluded.

Inclusion Criteria

My lymphoma is measurable by specific medical criteria.

Must have a negative serum pregnancy test

It has been at least 90 days since my stem cell transplant.

Exclusion Criteria

Is pregnant or lactating

Has inadequate venous access

I have another type of cancer that is currently active.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

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

1 week

Treatment

Participants receive a single dose of P-CD19CD20-ALLO1 CAR-T cells following conditioning chemotherapy

4 weeks

Weekly visits for safety and response assessments

Follow-up

Participants are monitored for safety, tolerability, and response after treatment

36 months

Regular visits for monitoring adverse events and response

Long-term follow-up

Participants are monitored for long-term effects and overall survival

15 years

What Are the Treatments Tested in This Trial?

Interventions

• P-CD19CD20-ALLO1

Trial Overview

The trial is testing P-CD19CD20-ALLO1 allogeneic CAR-T cells along with Rimiducid in patients with B cell cancers that came back or didn't respond after treatment. It's a Phase 1 study where doses will be increased gradually to find the safest dose that works.

How Is the Trial Designed?

Group I: P-CD19CD20-ALLO1 CAR-T Cells (Arm S) Experimental Treatment 2 Interventions

P-CD19CD20-ALLO1 following conditioning chemotherapy regimen S. Rimiducid may be administered.

Group II: P-CD19CD20-ALLO1 CAR-T Cells (Arm LD 750) Experimental Treatment 2 Interventions

P-CD19CD20-ALLO1 following conditioning chemotherapy regimen LD 750. Rimiducid may be administered.

Group III: P-CD19CD20-ALLO1 CAR-T Cells (Arm LD 1000) Experimental Treatment 2 Interventions

P-CD19CD20-ALLO1 following conditioning chemotherapy regimen LD 1000. Rimiducid may be administered.

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 clinical trial involving 10 patients with B-cell malignancies that persisted after allogeneic hematopoietic stem cell transplantation, treatment with genetically modified T cells targeting the CD19 antigen led to tumor regressions in three patients, including one achieving complete remission.

The study demonstrated that these allogeneic anti-CD19-CAR T cells can effectively target and reduce B-cell malignancies without causing graft-versus-host disease (GVHD), a common complication in such treatments, indicating a promising safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Kochenderfer, JN., Dudley, ME., Carpenter, RO., et al.[2023]

Engineered CD19-chimeric antigen receptor (CAR) T cells can safely target and treat CD19-positive B-cell malignancies that have relapsed after allogeneic stem cell transplantation.

This study highlights the potential of using donor-derived allogeneic T cells in combination with CAR technology to improve treatment outcomes for patients with these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donating used CARs. Rapoport, AP.[2021]

In a phase 1 study involving 12 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), the autologous CD19-CAR T-cell therapy was well tolerated, with low rates of cytokine release syndrome (6 patients) and neurotoxicity (3 patients).

75% of the patients achieved a minimal residual disease-negative complete response in the bone marrow, although higher disease burden before treatment was linked to more side effects and lower response rates, emphasizing the importance of pre-infusion disease status on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Talleur, AC., Qudeimat, A., Métais, JY., et al.[2022]

In a study of 35 patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic stem cell transplantation, 85.7% achieved complete remission after receiving CD19-targeted CAR T cell therapy, indicating high initial efficacy.

However, the long-term outcomes were concerning, with a recurrence rate of 68.3% at 18 months and an overall survival rate of only 30.0%, suggesting that additional treatments may be necessary to improve long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Chen, YH., Zhang, X., Cheng, YF., et al.[2021]

Infusing donor-derived T cells that are engineered to target the B-cell antigen CD19 can enhance the antitumor effect in patients with high-risk B-cell malignancies after stem-cell transplantation, while minimizing the risk of graft-versus-host disease.

The study demonstrated that T cells could be modified to reduce alloreactive responses through a process called alloanergization, allowing them to maintain their cancer-fighting abilities without increasing toxicity, which could lead to better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining CD19 redirection and alloanergization to generate tumor-specific human T cells for allogeneic cell therapy of B-cell malignancies. Davies, JK., Singh, H., Huls, H., et al.[2021]

In a study of 43 patients with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) who relapsed after an allotransplant, 79% achieved complete remission after receiving allogeneic anti-CD19 CAR-T cells, indicating high efficacy of this treatment.

While the therapy was effective, it was associated with a high incidence of cytokine release syndrome (CRS) in 88% of patients, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. Zhang, C., Wang, XQ., Zhang, RL., et al.[2021]

The study introduces a dual allogeneic CAR T cell targeting both CD20 and CD22, which shows strong and sustained activity against B-cell non-Hodgkin lymphoma (B-NHL) in laboratory and animal models, addressing the issue of tumor antigen escape.

This new approach offers a promising alternative to traditional autologous CAR T cell therapies by potentially providing 'off-the-shelf' treatment options that can effectively target tumors with varying levels of CD20 and CD22 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evidence of an Allogeneic Dual CD20xCD22 CAR to Target a Broad Spectrum of Patients with B-cell Malignancies. Aranda-Orgilles, B., Chion-Sotinel, I., Skinner, J., et al.[2023]

Allogeneic CAR+ Vδ1 γδ T cells targeting the CD20 antigen showed promising antitumor activity against B-cell tumors in preclinical studies, demonstrating both innate and adaptive immune responses.

These engineered T cells did not cause graft-versus-host disease in immunodeficient mice, suggesting a safer profile for potential clinical use in patients with B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic CD20-targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B-cell lymphoma models. Nishimoto, KP., Barca, T., Azameera, A., et al.[2022]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

In a study involving nine patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) and low donor chimerism after allogeneic stem cell transplant, autologous anti-CD19 CAR T cell therapy successfully restored complete donor chimerism in vitro after 12 days of culture.

The therapy showed strong cytotoxic effects against leukemia cells, with most patients experiencing mild cytokine release syndrome as the main adverse event, and two out of three treated patients achieving complete response without acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Level Donor Chimerism of CD19 CAR-T Cells Returned to Complete Donor Chimerism in Patients with Relapse After Allo-Hematopoietic Stem Cell Transplant. Li, Q., Mu, J., Yuan, J., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06014762

NCT06014762 | P-CD19CD20-ALLO1 Allogeneic CAR-T ...

Phase 1 study consisting of two parts. Part 1 is a weight-based dose escalation following a 3+3 design of dose-escalating cohorts to define a maximum ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e19530

Safety and efficacy of allogeneic CAR-T cells in B- ...

Allogeneic CAR-T therapy has demonstrated acceptable efficacy and safety in B cell malignancies, with CR being reported in about 60% of patients and GVHD in < ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497124075633

P-CD19CD20-ALLO1: Potent Fully Allogeneic CAR-T ...

P-CD19CD20-ALLO1, a dual-targeting, fully allogeneic TSCM-rich CAR-T product for CD19 and CD20-positive B-cell malignancies, demonstrates robust ...

4.

ashpublications.org

ashpublications.org/bloodadvances/article/9/7/1644/535452/Allogeneic-off-the-shelf-CAR-T-cell-therapy-for

Allogeneic off-the-shelf CAR T-cell therapy for relapsed or ...

EFS at 36 months was 70% for patients with non-Hodgkin lymphoma and 33% for patients with B-ALL (Figure 3C). OS at 36 months was 92% for ...

5.

poseida.com

poseida.com/wp-content/uploads/2024/12/4805.pdf

P-CD19CD20-ALLO1

Dual-targeting P-CD19CD20-ALLO1 CAR-T cells show higher and more durable killing over three rechallenges (indicated by the black arrows) with Raji cells than ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39908482/

Allogeneic off-the-shelf CAR T-cell therapy for relapsed or ...

Overall survival of all patients was 81% at 12 months and 75% at 36 months. Postinfusion expansion and persistence were limited, and CAR EBV- ...