IMPT-314 for Non-Hodgkin's Lymphoma

Recruiting at 27 trial locations

Overseen By Lyell Immunopharma Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lyell Immunopharma, Inc.

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Active CNS involvement, Cardiac lymphoma, 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: 1 day

270 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IMPT-314 for individuals with aggressive Non-Hodgkin's Lymphoma, a type of blood cancer. Researchers aim to determine the safety and effectiveness of this treatment, particularly for those whose cancer has not responded well to previous therapies. Participants should have tried at least two different treatments and still have cancer that is either recurring or not improving. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the opportunity to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial requires that you stop certain medications before enrolling. You must not have received any systemic therapy within 2 weeks, specific immune therapies within 3 half-lives, fludarabine within 12 weeks, and other specified treatments within certain time frames before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that IMPT-314, a new treatment for aggressive large B-cell lymphoma, has produced promising results in early studies. In one study, 94% of patients who had not previously tried CAR T therapy responded to IMPT-314, with 71% achieving a complete response, meaning their cancer was undetectable after treatment.

While these results are encouraging, it is important to remember that this treatment remains under investigation. Side effects may occur, and anyone considering joining a trial should discuss potential risks with their doctors. Ongoing studies aim to better understand the safety of IMPT-314 in a larger patient population. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about IMPT-314 for treating Non-Hodgkin's Lymphoma because it represents a fresh approach using a mechanism called CAR T-cell therapy. This treatment is unique because it modifies a patient's own T-cells to better recognize and attack cancer cells, which is different from traditional chemotherapy or radiation therapies that don't specifically target cancer cells. IMPT-314 aims to provide a more focused and potentially less toxic treatment option. Additionally, it holds promise for patients who have not responded well to existing therapies, offering new hope for those with limited options.

What evidence suggests that IMPT-314 might be an effective treatment for Non-Hodgkin's Lymphoma?

Research has shown that IMPT-314, a type of CAR T-cell therapy, could effectively treat aggressive large B-cell lymphoma. In earlier studies, 94% of patients who had not previously received CAR T-cell therapy responded to the treatment, and 71% achieved a complete response, with no signs of cancer detected. In this trial, participants will be divided into different cohorts, including those who are CAR T naïve and those with refractory disease or relapse. This therapy targets two proteins, CD19 and CD20, on the surface of cancer cells. By focusing on both proteins, it may more effectively destroy cancer cells. Early results are promising, suggesting that IMPT-314 could be a strong option for people with this type of lymphoma. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

Adults with aggressive B-cell Non-Hodgkin's Lymphoma who've had at least two prior treatments, including an anti-CD20 monoclonal antibody and chemotherapy. They must have a certain level of white blood cells, be in good physical condition (ECOG 0 or 1), and have relapsed or refractory disease after their last treatment. Not eligible if they've recently received other therapies, have ongoing major health issues like heart involvement by lymphoma, autoimmune diseases requiring strong medication within the past two years, or active cancer elsewhere.

Inclusion Criteria

Absolute neutrophil count (ANC) ≥ 1000/uL

At least 1 measurable lesion (the Lugano classification)

My lymphoma is aggressive and confirmed by a biopsy.

Exclusion Criteria

I have received certain treatments within specific time frames before joining.

I am facing an urgent cancer-related health issue.

My heart has been affected by lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive a conditioning chemotherapy regimen consisting of fludarabine and cyclophosphamide over 3 days

1 week

Treatment

Participants receive a single infusion of CAR-transduced autologous T cells

1 day

Active Post-Treatment

Participants remain in the active post-treatment period for monitoring

2 years

Long-term Follow-up

Participants continue in long-term follow-up for safety and efficacy monitoring

15 years

What Are the Treatments Tested in This Trial?

Interventions

• IMPT-314

Trial Overview The trial is testing IMPT-314, a new CAR T-cell therapy targeting CD19 and CD20 on cancer cells. It involves modifying a patient's own T-cells to fight cancer and giving them back via infusion after chemotherapy with fludarabine and cyclophosphamide. The study has two phases: Phase 1 for dose finding (60 patients) and Phase 2 for further safety/efficacy evaluation (40 additional participants).

How Is the Trial Designed?

Group I: Phase 2 CAR T naïve (Cohort 1) Experimental Treatment 3 Interventions

Single dose determined during Phase 1.

Group II: Phase 1 Refractory disease or relapse within one year of first-line therapy (Cohort 3) Experimental Treatment 3 Interventions

Group III: Phase 1 Receiving first-line treatment for high-risk large B-cell lymphoma (Cohort 5) Experimental Treatment 3 Interventions

Group IV: Phase 1 Received T-cell engager (TCE) therapy (Cohort 4) Experimental Treatment 3 Interventions

Group V: Phase 1 CAR T naïve (Cohort 1) Experimental Treatment 3 Interventions

Group VI: Phase 1 CAR T experienced (Cohort 2) Experimental Treatment 3 Interventions

IMPT-314 is already approved in United States for the following indications:

Approved in United States as IMPT-314 for:

• Relapsed or refractory aggressive B-cell lymphoma
• High-grade B-cell lymphoma (HGBCL)
• Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS)
• Primary mediastinal B-cell lymphoma
• DLBCL arising from follicular lymphoma

Who Is Running the Clinical Trial?

Lyell Immunopharma, Inc.

Lead Sponsor

Trials

5

Recruited

610+

ImmPACT Bio

Lead Sponsor

Trials

2

Recruited

150+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4824/533295/First-Results-of-IMPT-314-an-Autologous-Bispecific

First Results of IMPT-314, an Autologous Bispecific CD19 ... Patients received a median of 2.5 prior lines of therapy (range 2-6), and 41.7% (5/12) of patients received bridging therapy. The efficacy ...

2. ir.lyell.com ir.lyell.com/news-releases/news-release-details/lyell-presents-positive-initial-clinical-data-phase-1-2-clinical

Lyell Presents Positive Initial Clinical Data from the Phase ... Objective response rate (ORR) of 94% and a complete response (CR) rate of 71% demonstrated after IMPT-314 treatment in CAR T-naïve patients ...

3. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/LYL314-101

IMPT-314 in Aggressive B-Cell Non-Hodgkin Lymphoma The purpose of this study is to evaluate experimental gene-modified immune cells called IMPT-314 for the treatment of lymphomas that have either come back after ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05826535

Study of LYL314 in Aggressive Large B-Cell Lymphoma This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of LYL314, a dual-targeting chimeric antigen receptor (CAR)

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123134884

A CD19/CD20-Directed Bispecific CAR-T Cell Therapy in ... A Phase 1/2 multicenter, open label study to evaluate the safety and efficacy of IMPT-314 in participants with relapsed/refractory aggressive B-cell NHL.