SynKIR-310 for Non-Hodgkin's Lymphoma

Recruiting at 5 trial locations

Overseen By Physician Connect

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Verismo Therapeutics

Must not be taking: Investigational agents

Disqualifiers: Immunodeficiency, CNS disorder, cardiac issues, 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: 1

Duration: 1 day

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called SynKIR-310, a type of cell therapy, to determine its safety and effectiveness for individuals with Non-Hodgkin's Lymphoma (NHL) that has returned or not responded to previous treatments. Participants will receive a single dose of SynKIR-310 through an IV. The trial seeks individuals diagnosed with B-NHL who have tried at least two previous treatments without success or have relapsed. It specifically targets those who have relapsed after certain stem cell transplants and have a measurable tumor. As a Phase 1 trial, the research focuses on understanding how the treatment works 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 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.

Is there any evidence suggesting that SynKIR-310 is likely to be safe for humans?

Research shows that SynKIR-310 remains in the early stages of testing to assess its safety in humans. SynKIR-310 is a type of CAR-T cell therapy, which uses a person's own immune cells to fight cancer. Similar treatments have shown both promise and some risks.

For SynKIR-310, limited safety data exists because it is in the first phase of trials. This phase primarily evaluates the treatment's safety for patients. While many have tolerated other CAR-T therapies well, they can sometimes cause side effects like fever or low blood pressure. These side effects can vary from person to person.

Since SynKIR-310 resembles other CAR-T treatments, it might have similar outcomes, but no specific data is available yet. Anyone considering joining the trial should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about SynKIR-310 for treating Non-Hodgkin's Lymphoma because it represents a novel approach compared to traditional treatments like chemotherapy and radiation. Unlike these standard methods that often target both healthy and cancerous cells, SynKIR-310 is a form of targeted immunotherapy, which aims to harness the body's own immune system to specifically attack lymphoma cells. This single-dose IV administration could potentially offer a more precise and less harmful alternative, minimizing side effects while maximizing effectiveness against the cancer.

What evidence suggests that SynKIR-310 might be an effective treatment for Non-Hodgkin's Lymphoma?

Research shows that SynKIR-310, a type of CAR-T cell therapy, may help treat relapsed or refractory B-cell Non-Hodgkin Lymphoma (B-NHL). In an earlier study, 73.4% of patients experienced a complete response, with their cancer no longer detectable. Another 13.3% showed a partial response, with significant cancer reduction. In this trial, participants will receive a single dose IV administration of SynKIR-310. CAR-T therapies like SynKIR-310 work by reprogramming a person’s own immune cells to find and destroy cancer cells. These early results are promising, suggesting that SynKIR-310 could be a good option for those unresponsive to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Laura A Johnson, PhD

Principal Investigator

Verismo Therapeutics

Are You a Good Fit for This Trial?

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

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.

My diagnosis of B-cell Non-Hodgkin Lymphoma is confirmed by tissue analysis.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• SynKIR-310

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.

How Is the Trial Designed?

Group I: SynKIR-310 Experimental Treatment 1 Intervention

Single dose IV administration of SynKIR-310

SynKIR-310 is already approved in United States for the following indications:

Approved in United States as SynKIR-310 for:

• Relapsed/Refractory B-cell Non-Hodgkin Lymphomas (B-NHL)
• Diffuse Large B Cell lymphoma (DLBCL)
• Follicular Lymphoma (FL)
• Mantle Cell Lymphoma (MCL)
• Marginal Zone Lymphoma (MZL)

Who Is Running the Clinical Trial?

Verismo Therapeutics

Lead Sponsor

Trials

4

Recruited

120+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

CD19-directed autologous CAR T cell therapy has shown remarkable effectiveness in treating relapsed and refractory non-Hodgkin lymphoma (NHL), leading to significant response rates and prolonged remissions, which has resulted in FDA approval for four CAR T cell products from 2017 to 2021.

Due to its success, there is growing interest in using autologous CAR T cells earlier in treatment for large B cell lymphoma, highlighting the need for ongoing management of associated toxicities and the exploration of allogeneic CAR T options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Based Therapies in Lymphoma: A Review of Current Practice and Perspectives. Sheikh, S., Migliorini, D., Lang, N.[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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06544265

NCT06544265 | SynKIR-310 for Relapsed/Refractory B-NHL This is a Phase 1, FIH, multicenter, open-label study of a single infusion of SynKIR-310 in participants with relapsed/refractory B-NHL.

2. synapse.patsnap.com synapse.patsnap.com/drug/c69770ec606c4ad9a2b2ada527b830e2

SynKIR-310 - Drug Targets, Indications, Patents A Phase 1 Study of SynKIR-310, Autologous T Cells Transduced With CD19 KIR-CAR, in Participants With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma.

3. cgtlive.com cgtlive.com/view/verismo-therapeutics-trial-car-t-synkir-310-doses-patient-follicular-lymphoma

Verismo Therapeutics' Trial for CAR-T SynKIR-310 Doses ... Out of the 13 patients who responded to the CAR-T product, 11 patients (73.4%) achieved a complete response (CR) and 2 patients (13.3%) achieved ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6880960/

CAR-T cell Therapy for Non-Hodgkin Lymphomas The purpose of this review is to summarize the clinical efficacy and unique toxicities of individually developed CAR-T cell products for the treatment of ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910607

Use of CAR-Transduced Natural Killer Cells in CD19 ... For example, CAR T cells directed against CD19 induce remissions in 68 to 93% of patients with acute B-lymphoblastic leukemia, in 57 to 71% of ...

6. nature.com nature.com/articles/s41591-023-02785-8

Safety, efficacy and determinants of response of allogeneic ... Autologous anti-CD19 CAR-T cells induce remissions in most patients with B cell malignancies. However, CAR-T cells have limitations ...