SynKIR-310 for Non-Hodgkin's Lymphoma

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Verismo Therapeutics

Must not be taking: Investigational agents

Disqualifiers: Immunodeficiency, CNS disorder, cardiac issues, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This first-in-human (FIH) trial is designed to assess the safety, feasibility and preliminary efficacy of a single intravenous (IV) dose of SynKIR-310 administered to participants with relapsed/refractory B-NHL.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment SynKIR-310 for Non-Hodgkin's Lymphoma?

Research shows that T cells engineered to recognize CD19, a marker on B cells, have been effective in treating B-cell lymphomas, leading to significant tumor reduction and prolonged absence of B cells in patients. This suggests that SynKIR-310, which uses a similar approach, may also be effective for Non-Hodgkin's Lymphoma. ^{1 2 3 4 5}

What safety data exists for SynKIR-310 or similar treatments in humans?

The treatment, similar to SynKIR-310, has shown promising results in treating certain blood cancers, but it can cause significant side effects like cytokine-release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). These side effects are being managed with medications like tocilizumab and corticosteroids, and ongoing research aims to reduce these risks. ^{1 6 7 8 9}

How is the treatment SynKIR-310 different from other treatments for non-Hodgkin's lymphoma?

SynKIR-310 is unique because it uses a patient's own T cells that are genetically modified to target CD19, a protein on lymphoma cells, which allows for precise targeting and killing of cancer cells. This approach is part of a broader category of CAR T-cell therapies that have shown promising results in treating relapsed or refractory non-Hodgkin's lymphoma, offering a new option for patients who do not respond to traditional treatments. ^{1 3 4 8 10}

Research Team

Laura A Johnson, PhD

Principal Investigator

Verismo Therapeutics

Eligibility Criteria

This trial is for adults over 18 with B-cell Non-Hodgkin's Lymphoma (B-NHL) who have tried at least two treatments or can't/won't get CAR T therapy. They should have relapsed or not responded after treatment, including stem cell transplants done over six months ago. Participants need to be fairly active and healthy overall (ECOG status 0-1).

Inclusion Criteria

I am 18 years old or older.

My condition did not improve after two previous treatments.

I had a stem cell transplant over 6 months ago and do not have graft versus host disease.

Exclusion Criteria

Known immunodeficiency disease

I do not have any ongoing serious infections.

Previously treated with any investigational agent within 30 days prior to screening

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous (IV) dose of SynKIR-310

1 day

1 visit (in-person)

Dose Escalation

Doses are escalated across 2 cohorts to determine a Recommended Phase 2 Dose (RP2D)

Varies

Dose Expansion

Additional participants are enrolled at the RP2D to further characterize safety, feasibility, and preliminary efficacy

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Treatment Details

Interventions

• SynKIR-310 (CAR T-cell Therapy)

Trial Overview The trial tests SynKIR-310, a new drug given through IV once to see if it's safe and works against different types of B-NHL that haven't improved with standard treatments.

Participant Groups

Group I: SynKIR-310 Experimental Treatment 1 Intervention

Single dose IV administration of SynKIR-310

Who Is Running the Clinical Trial?

Verismo Therapeutics

Lead Sponsor

Trials

4

Recruited

120+

Findings from Research

A new CAR immunotherapy targeting CD4 has been developed using NK-92 cells, showing strong effectiveness in eliminating CD4+ T-cell leukemia and lymphoma cell lines, as well as patient samples in laboratory tests.

In animal models, CD4CAR NK-92 cells significantly improved survival by effectively targeting and destroying difficult-to-access lymphoma nodules, suggesting a promising new treatment strategy for aggressive peripheral T-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. Pinz, KG., Yakaboski, E., Jares, A., et al.[2023]

CAR19-engineered invariant natural killer T (iNKT) cells show enhanced anti-lymphoma activity compared to traditional CAR19-T cells, leading to improved tumor-free and overall survival in both laboratory and animal studies.

The combination of CAR19-iNKT cells with all-trans retinoic acid further boosts their effectiveness against CD19+ chronic lymphocytic leukemia, suggesting a promising new approach for treating lymphomas and potentially other cancers that express CD1d.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting. Rotolo, A., Caputo, VS., Holubova, M., et al.[2021]

In a study involving 4 patients with recurrent lymphoma, CAR-redirected autologous CTL therapy showed no overt toxicities from the treatment, indicating a favorable safety profile for this immunotherapeutic approach.

However, the effectiveness of the therapy was limited by the short persistence of the transferred CTLs in the patients' circulation, lasting only 24 hours to 7 days, highlighting the need for strategies to enhance T cell survival and reduce immune rejection responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Jensen, MC., Popplewell, L., Cooper, LJ., et al.[2022]

Adoptive T-cell therapy using anti-CD19 chimeric antigen receptor (CAR)-expressing T cells showed strong effectiveness in eliminating lymphoma cells in a murine model, with complete eradication of normal B cells lasting for at least 143 days after treatment.

The success of the anti-CD19-CAR-transduced T cells in fighting lymphoma was significantly enhanced by pre-treatment irradiation of the mice, and these CAR T cells outperformed the original anti-CD19 monoclonal antibody in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Kochenderfer, JN., Yu, Z., Frasheri, D., et al.[2023]

The treatment of a patient with advanced follicular lymphoma using genetically modified T cells expressing a CAR targeting CD19 resulted in a dramatic regression of the lymphoma and a selective elimination of B-cell precursors from the bone marrow.

This approach led to the absence of blood B cells for at least 39 weeks post-infusion, indicating a successful and prolonged antigen-specific eradication of B-lineage cells, which was not solely due to the prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Kochenderfer, JN., Wilson, WH., Janik, JE., et al.[2023]

CAR T-cell therapy, particularly targeting CD19, has shown promising results in treating B-cell malignancies like B-ALL, with high rates of remission reported in clinical trials.

Despite its effectiveness, CAR T-cell therapy carries risks of significant neurotoxicity and cytokine release syndrome, necessitating careful management and further research to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular Immunotherapy in B-Cell Malignancy. Schwarzbich, MA., Witzens-Harig, M.[2018]

CAR T cell therapy targeting CD19 has shown remarkable efficacy in treating relapsed and refractory B-cell acute lymphoblastic leukemia, with most patients achieving complete remissions.

Despite its effectiveness, CAR T cell therapy is associated with significant risks of toxicity, including cytokine-release syndrome and neurotoxicity, which can be managed with treatments like tocilizumab and corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted T Cells for Hematologic Malignancies: Clinical Experience to Date. Davila, ML., Sauter, C., Brentjens, R.[2018]

Allogeneic non-viral cytokine-induced killer (CIK) cells engineered with the Sleeping Beauty transposon to express CD19CAR showed promising results in preclinical models, achieving complete tumor eradication in relapsed acute lymphoblastic leukemia (ALL) and lymphoma.

The infusion of CARCIK-CD19 cells was found to be safe and well tolerated, with the cells persisting in the body and maintaining functionality, indicating potential for effective treatment in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy and Safety of CD19CAR Cytokine-Induced Killer Cells Transfected with Sleeping Beauty Transposon for the Treatment of Acute Lymphoblastic Leukemia. Magnani, CF., Mezzanotte, C., Cappuzzello, C., et al.[2019]

In a phase I/II trial involving 13 patients with B cell acute lymphoblastic leukemia (B-ALL) who relapsed after stem cell transplantation, donor-derived CD19 CAR T cells showed promising results, with 6 out of 7 patients receiving the highest doses achieving complete remission (CR) or CR with incomplete blood count recovery (CRi) by day 28.

The CAR T cell therapy demonstrated a favorable safety profile, with only mild cytokine-release syndrome reported and no severe toxicities such as graft-versus-host disease or neurotoxicity, indicating that this approach could be a viable treatment option for relapsed B-ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities. Magnani, CF., Gaipa, G., Lussana, F., et al.[2021]

References

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

Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. [2023]

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

Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting. [2021]

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

Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. [2022]

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

Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. [2023]

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

Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. [2023]

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

Cellular Immunotherapy in B-Cell Malignancy. [2018]

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

CD19-Targeted T Cells for Hematologic Malignancies: Clinical Experience to Date. [2018]

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

Preclinical Efficacy and Safety of CD19CAR Cytokine-Induced Killer Cells Transfected with Sleeping Beauty Transposon for the Treatment of Acute Lymphoblastic Leukemia. [2019]

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

Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

CAR T-Based Therapies in Lymphoma: A Review of Current Practice and Perspectives. [2023]