NT-I7 + CAR T-Cell Therapy for Large B-Cell Lymphoma

No longer recruiting at 4 trial locations

Overseen By Kristina Stermer, MMS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NeoImmuneTech

Must not be taking: Chemotherapy, Biologic therapy

Disqualifiers: CNS involvement, Autoimmune disease, Active infection, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NT-I7, administered after CAR T-cell therapy. The focus is on large B-cell lymphoma, a form of blood cancer that has not responded well to other treatments. Researchers aim to determine if NT-I7 is safe and effective at shrinking tumors when used after CAR T-cell therapy. Individuals with this specific type of lymphoma who are eligible for CAR T-cell therapy might be suitable candidates for this trial. 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 treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment. Non-cancer-related medications, like insulin for diabetes, are allowed.

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

Research has shown that NT-I7, when used after CAR T-cell therapy, is generally safe and well-tolerated. Studies found that patients with advanced diffuse large B-cell lymphoma (a type of blood cancer) tolerated doses up to 480 micrograms per kilogram without serious issues. Early results indicate that NT-I7 has a manageable safety profile, with no reported cases of cytokine release syndrome, a common side effect of similar treatments. This suggests NT-I7 might be a safe addition to CAR T-cell therapy for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for large B-cell lymphoma, which typically involve CAR-T cell therapies like Kymriah, Yescarta, or Breyanzi, NT-I7 offers a unique approach by enhancing and sustaining the immune response after CAR-T infusion. NT-I7 is an innovative cytokine that boosts T-cell survival and proliferation, potentially leading to longer-lasting cancer control. Researchers are excited about NT-I7 because it could improve the effectiveness and durability of existing CAR-T therapies, providing patients with a more robust and sustained defense against their cancer.

What evidence suggests that NT-I7 after CAR-T infusion could be effective for large B-cell lymphoma?

In this trial, participants will receive NT-I7 following CAR T-cell therapy, which has shown promising results for treating large B-cell lymphoma. Research indicates that using NT-I7 after CAR T-cell therapy can help maintain the treatment's benefits. In one study, 88% of patients maintained their positive response for more than six months. Another study found that 81.1% of patients with recurring lymphoma experienced an objective response, meaning their cancer shrank or disappeared. NT-I7 appears to enhance the effectiveness of CAR T-cell therapy by boosting the body's immune system. Overall, these findings suggest that NT-I7 could be a helpful addition to CAR T-cell therapy for this type of lymphoma. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with relapsed/refractory Large B-cell Lymphoma who've had at least two prior treatments and are eligible for CD19 CAR T-cell therapy. They must have an ECOG performance status of 0-1, measurable disease, a life expectancy of 12+ weeks, and adequate organ function. Exclusions include severe reactions to previous CAR T-cell therapy, pregnancy, CNS lymphoma involvement, active infections or concurrent clinical study participation.

Inclusion Criteria

Hemoglobin ≥8.0 g/dL or ≥4.96 mmol/L

Subjects must have measurable disease by IWG response criteria for lymphoma [Lugano classification (3)]

AST(SGOT)/ALT(SGPT) ≤2.5 × ULN (AST and/or ALT ≤5 × ULN for subjects with liver metastasis)

Exclusion Criteria

Pregnant, lactating or breastfeeding or expecting to conceive or father children within the study duration from screening through 120 days after the last dose of study treatment

I cannot receive treatments by injection into my muscles.

Concurrent enrollment in another clinical study unless it is an observational (noninterventional) clinical study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects are enrolled in 1 of 7 dose levels to determine the maximum tolerated dose of NT-I7

3 weeks

Multiple visits for dose administration and monitoring

Dose Expansion

Up to 15 subjects are treated with the recommended dose identified in the Dose Escalation phase

3 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Periodic visits for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• NT-I7

Trial Overview The trial is testing the safety and effectiveness of NT-I7 (Efineptakin alfa) given after standard CD19 CAR T-cell therapies like Axicabtagene ciloleucel, Lisocabtagene Maraleucel or Tisagenlecleucel in patients with r/r LBCL. It's a Phase 1b multicenter study focusing on how well patients tolerate this combination treatment.

How Is the Trial Designed?

Group I: NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion Experimental Treatment 4 Interventions

CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.

Who Is Running the Clinical Trial?

NeoImmuneTech

Lead Sponsor

Trials

16

Recruited

780+

Published Research Related to This Trial

IL-7/IL-7Rα-Fc treatment significantly inhibited tumor growth and improved survival in murine lung cancer models by enhancing the activity of antigen presenting cells (APCs) and T cells.

The mechanism of action involves increased levels of key cytokines (CXCL9, CXCL10, IFNγ, IL-12) and a shift towards a more effective immune response, characterized by M1 macrophage infiltration and enhanced T cell activation, which are crucial for the antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of CXCR3 ligands in IL-7/IL-7R alpha-Fc-mediated antitumor activity in lung cancer. Andersson, A., Srivastava, MK., Harris-White, M., et al.[2022]

In a study using a lymphopenic murine melanoma model, recombinant IL7-Fc significantly improved the effectiveness of adoptive cell therapy (ACT) by increasing the number of CD8+ T cells in tumors and enhancing tumor growth inhibition.

However, in an immunocompetent murine melanoma model, IL7-Fc reduced the effectiveness of ACT by promoting the expansion of endogenous T cells, which limited the proliferation of the transferred tumor-reactive T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model. Yu, EM., Cho, E., Singh, R., et al.[2021]

A new long-acting form of interleukin-7 (rhIL-7-hyFc) has been shown to significantly enhance the effectiveness of CAR T cell therapy by promoting the growth, persistence, and cytotoxicity of CAR T cells in mouse models.

This enhancement leads to long-term tumor-free survival, suggesting that rhIL-7-hyFc could be a valuable addition to CAR T cell treatments for patients with refractory hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. Kim, MY., Jayasinghe, R., Devenport, JM., et al.[2023]

A single subcutaneous dose of recombinant human IL-7 (rhIL-7) was well tolerated in HIV-infected individuals, showing biological activity at a dose of 3 microg/kg and a maximum tolerated dose of 30 microg/kg, with mild side effects like injection site reactions and transient liver function test elevations.

rhIL-7 administration led to increased numbers of circulating CD4(+) and CD8(+) T cells, indicating its potential to enhance T cell recovery in HIV infection, although it also caused transient increases in plasma HIV-RNA levels in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Sereti, I., Dunham, RM., Spritzler, J., et al.[2021]

IL-7 plays a crucial role in regulating B-cell development by suppressing premature Ig light-chain rearrangement, which is essential for proper antibody formation.

In a study examining human CD19⁺ cells in xenogeneic cultures, it was found that less than 10% of these cells had complete IGH rearrangements, indicating that IL-7 signaling is vital for the correct timing of immunoglobulin gene rearrangement during B-cell maturation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells. Nodland, SE., Berkowska, MA., Bajer, AA., et al.[2021]

The study of hIL-7-hyFc, involving 30 healthy volunteers, demonstrated that this treatment significantly increased lymphocyte counts, particularly T-cells, with effects peaking three weeks post-administration and lasting for several weeks.

hIL-7-hyFc was well-tolerated with minimal side effects, primarily injection site reactions that resolved on their own, suggesting it could be a safe and effective option for patients with weakened T-cell immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. Lee, SW., Choi, D., Heo, M., et al.[2021]

The hybrid Fc-fused long-acting recombinant human IL-7 (rhIL-7-hyFc) significantly enhances the antitumor response by expanding CD8+ T cells in the tumor microenvironment, leading to increased tumor-reactive T cells with improved effector functions.

When combined with chemotherapy and checkpoint inhibitors, rhIL-7-hyFc not only boosts the antitumor response but also restores CD8+ T cell levels even in conditions of low T lymphocyte counts, suggesting its potential as an effective immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. Kim, JH., Kim, YM., Choi, D., et al.[2022]

In a study involving 18 patients with recurrent glioblastoma, treatment with a long-acting engineered version of interleukin-7 (rhIL-7-hyFc) significantly increased total lymphocyte count (TLC) from an average of 1131 cells/mm3 to 4356 cells/mm3, indicating its efficacy in restoring immune function.

The treatment was well-tolerated, showing no serious toxicity, and resulted in a median overall survival of 378 days and progression-free survival of 231 days, suggesting potential benefits when combined with various chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compassionate use of recombinant human IL-7-hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma. Ahn, S., Park, JS., Kim, H., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS7596

Trial in progress: A phase 1b study evaluating the safety ... A phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 (efineptakin alfa), a long-acting human IL-7, post- ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02376-7/fulltext

806MO Phase Ib study of NT-I7 (efineptakin alfa), a long- ... NT-I7 treatment post CAR T is safe and well tolerated in pts with advanced DLBCL up to 480 μg/kg (DL5). NT-I7 enhances all CAR T factors associated with ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2621

A phase 2a study of NT-I7 (efineptakin alfa), a long-acting ... NT-I7, a long-acting IL-7, in combination with pembrolizumab (pembro) has shown to significantly increase intratumoral T cell infiltration and elicit some ...

4. neoimmunetech.com neoimmunetech.com/en/irpr/news/984

NeoImmuneTech Announces Final Topline Results of ... Notably, 88% of patients (7 out of 8) maintained their response beyond 6 months, demonstrating the potential of NT-I7 to sustain CAR-T efficacy ...

5. onclive.com onclive.com/view/nt-i7-after-car-t-cell-therapy-enhances-car-t-factors-in-r-r-dlbcl

NT-I7 After CAR T-Cell Therapy Enhances CAR T Factors ... NT-I7 with CAR T-cell therapy demonstrated an 81.1% objective response rate in relapsed DLBCL patients and a manageable safety profile.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05075603

Relapsed/Refractory Large B-cell Lymphoma With NT-I7 ... This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/neoimmunetech-trial-car-t-therapy/

NeoImmuneTech presents data from trial of CAR-T therapy ... The interim results highlighted that mid-level doses of NT-I7 (360, 480 µg/kg) maintained a stable safety profile. No cases of cytokine release ...