BAFFR-targeting CAR T Cells for B-Cell Lymphoma

Recruiting at 3 trial locations

Overseen By DeShaun Noakes, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: PeproMene Bio, Inc.

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, Cardiac conditions, Neurologic conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day (infusion)

36 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic steroids or chronic immunosuppressants. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment BAFFR-targeting CAR T Cells for B-Cell Lymphoma?

Research shows that BAFFR-targeting CAR T cells can effectively kill B-cell cancers, including lymphoma, by targeting a specific marker (BAFF-R) on cancer cells. This treatment has been successful in overcoming challenges faced by other similar therapies, such as when cancer cells lose certain markers, making it a promising option for patients with relapsed or hard-to-treat B-cell cancers. ^{1 2 3 4 5}

What safety information is available for BAFFR-targeting CAR T cell therapy?

While specific safety data for BAFFR-targeting CAR T cells is not provided, CAR T cell therapies in general have shown significant safety concerns, including potentially serious side effects like cytokine release syndrome (a severe immune reaction) and on-target/off-tumor toxicity (where healthy tissues are mistakenly attacked). Researchers are actively working on strategies to improve the safety of these therapies. ^{6 7 8 9 10}

How is the BAFFR-CAR T cell treatment different from other treatments for B-cell lymphoma?

BAFFR-CAR T cells are unique because they target the BAFF-R receptor, which is a B-cell survival receptor highly expressed in B-cell malignancies, and can overcome the issue of CD19 antigen loss that limits the effectiveness of other CAR T cell therapies. This treatment specifically binds to three different receptors on B cells, reducing the chance of the cancer escaping detection and treatment. ^{1 2 3 11 12}

Research Team

Elizabeth Budde, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults with B-cell Non-Hodgkin's Lymphoma that has returned or didn't respond to at least one treatment can join. They must be physically capable (ECOG ≤ 2), have a certain level of organ function, and not be pregnant or breastfeeding. People who've had other cancers recently, major heart issues, immune deficiencies, uncontrolled infections, CNS lymphoma involvement within the last 3 months, or are on steroids/immunosuppressants can't participate.

Inclusion Criteria

Specific blood count requirements

AST < 3 x ULN

Left ventricular ejection fraction (LVEF) ≥ 45%

Exclusion Criteria

I have an ongoing infection that needs treatment with antibiotics or antifungals.

History of allergic reactions to compounds of similar composition to study agent

Primary immunodeficiency

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion to prepare for CAR T cell infusion

1 week

Treatment

Participants receive BAFFR-CAR T cells to target B-cell Non-Hodgkin's Lymphoma

1 day (infusion)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 15 years

Treatment Details

Interventions

• BAFFR-CAR T cells

Trial Overview The trial is testing BAFFR-CAR T cells in patients whose B-NHL has come back or hasn't responded to treatments. It's an early-phase study to see how safe it is and what effects it has on this type of lymphoma. Participants will receive genetically modified T cells designed to target and kill cancer cells.

Participant Groups

Group I: B-cell activating factor receptor-Chimeric antigen receptor T cells [BAFFR-CAR T cells] Experimental Treatment 1 Intervention

BAFFR-CAR T cells in participants with r/r B-NHL

Who Is Running the Clinical Trial?

PeproMene Bio, Inc.

Lead Sponsor

Trials

2

Recruited

60+

City of Hope Medical Center

Collaborator

Trials

614

Recruited

1,924,000+

Findings from Research

The development of BAFF-R CAR T cells shows promise in treating B cell malignancies, effectively targeting tumors even when CD19 expression is lost, which is a common issue with current therapies.

In preclinical models, BAFF-R CAR T cells successfully eradicated established tumors and demonstrated antitumor activity against relapsed cases of acute lymphoblastic leukemia (ALL) that had lost CD19 expression, suggesting a potential solution to tumor relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. Qin, H., Dong, Z., Wang, X., et al.[2020]

BAFF CAR-T cells, developed using a non-viral gene delivery method, effectively target and kill various B cell cancers, including mantle cell lymphoma, multiple myeloma, and acute lymphoblastic leukemia, both in laboratory settings and in animal models.

These CAR-T cells bind to three different BAFF receptors, which helps reduce the risk of cancer cells escaping treatment by losing the targeted antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers. Wong, DP., Roy, NK., Zhang, K., et al.[2023]

The novel BAFF-R CAR T-cell therapy shows promise in treating B-cell malignancies, particularly in cases where traditional CD19-targeted therapies may fail due to antigen loss, with effective elimination of BAFF-R expressing tumors demonstrated in mouse models.

This therapy has been developed under strict manufacturing standards and has passed necessary FDA testing, paving the way for a Phase 1 clinical trial in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor efficacy of BAFF-R targeting CAR T cells manufactured under clinic-ready conditions. Dong, Z., Cheng, WA., Smith, DL., et al.[2020]

BAFF-R is crucial for the maturation and survival of B cells, and its expression is found in most circulating human B cells and a small subset of T cells, indicating its importance in normal immune function.

In a study of 116 cases of B-cell lymphoproliferative disorders, 78% were BAFF-R-positive, suggesting that BAFF-R expression may be necessary for the survival of certain neoplastic B lymphocytes, similar to its role in healthy B-cell development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders. Rodig, SJ., Shahsafaei, A., Li, B., et al.[2015]

In a study of 32 patients with relapsed or refractory B cell non-Hodgkin lymphoma, bispecific CD19/22 CAR T cell therapy showed a high overall response rate of 79.3% and a complete response rate of 34.5%, indicating its potential efficacy as a treatment option.

While the therapy demonstrated promising results, it was associated with significant safety concerns, including severe cytokine release syndrome in 28.1% of patients and grade 3 or higher neurologic events in 12.5%, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Investigation of Bispecific CD19/22 CAR T Cell Therapy in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma. Zhang, Y., Li, J., Lou, X., et al.[2022]

CAR-T cell therapy has shown remarkable success in treating B-cell malignancies, but researchers are focused on improving its safety and effectiveness due to risks like cytokine release syndrome and off-target effects.

Innovative safety strategies, such as ON- and OFF-switch CARs and multi-antigen-targeting CAR-T cells, are being developed to enhance the persistence and reduce adverse events associated with CAR-T therapy, paving the way for a new generation of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Next-Generation CAR-T Cells for Better Toxicity Management. Andrea, AE., Chiron, A., Bessoles, S., et al.[2023]

CAR T cell therapy has shown great promise in treating certain blood cancers, but it can lead to serious side effects, including potentially fatal toxicities from cytokine release and off-target effects that harm healthy tissues.

Recent strategies to improve safety include modifying CAR structures and incorporating elements like switch molecules and suicide genes to reduce the toxic effects of CAR T cells on normal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for modifying the chimeric antigen receptor (CAR) to improve safety and reduce toxicity in CAR T cell therapy for cancer. Sayadmanesh, A., Yekehfallah, V., Valizadeh, A., et al.[2023]

Anti-CD19 CAR-modified T cells have demonstrated a 48% overall response rate in treating B-cell malignancies, with complete responses observed in 24% of patients across six phase I clinical trials involving 50 patients.

The study found that conditioning chemotherapy significantly improves progression-free survival (PFS), making it a crucial factor for enhancing the efficacy of CAR T-cell therapy, while the treatment was generally well tolerated with temporary adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. Zhu, Y., Tan, Y., Ou, R., et al.[2022]

CAR-T cell therapy has shown remarkable efficacy in treating B cell malignancies, including leukemia, lymphoma, and multiple myeloma, with high response rates, but it comes with significant safety concerns.

The most serious side effects of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require supportive care and specific treatments like tocilizumab and steroids to manage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. Chohan, KL., Siegler, EL., Kenderian, SS.[2023]

Adoptive cellular immunotherapy using anti-CD19 CAR-T cells has significantly improved treatment outcomes for patients with relapsed or refractory B cell lymphomas, leading to durable remissions, with two products already FDA-approved and a third in large clinical trials.

Despite their effectiveness, CAR-T cell therapies can cause serious side effects like infections and cytokine release syndrome, highlighting the need for better understanding of these toxicities and strategies to mitigate them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Kallam, A., Vose, JM.[2020]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

Chimeric antigen receptor (CAR) T-cell therapies, particularly those targeting CD19, have shown significant efficacy in treating B-cell malignancies, including aggressive forms like B-cell acute lymphoblastic leukemia and non-Hodgkin lymphomas.

Despite their success, many patients do not respond or relapse after treatment, prompting research into alternative CAR targets such as CD20, CD22, and others, as well as combination therapies to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cell Therapies for B-cell Lymphoid Malignancies: Identifying Targets Beyond CD19. Vanegas, YM., Mohty, R., Gadd, ME., et al.[2022]

References

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

CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Antitumor efficacy of BAFF-R targeting CAR T cells manufactured under clinic-ready conditions. [2020]

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

BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders. [2015]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Prospective Investigation of Bispecific CD19/22 CAR T Cell Therapy in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Engineering Next-Generation CAR-T Cells for Better Toxicity Management. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Strategies for modifying the chimeric antigen receptor (CAR) to improve safety and reduce toxicity in CAR T cell therapy for cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. [2022]

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

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. [2023]

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

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]

12. Saudi Arabia pubmed.ncbi.nlm.nih.gov

CAR-T cell Therapies for B-cell Lymphoid Malignancies: Identifying Targets Beyond CD19. [2022]