IPH6501 for Non-Hodgkin's Lymphoma

Recruiting at 14 trial locations

Overseen By Innate pharma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Innate Pharma

Must be taking: Anti-CD20 antibody

Disqualifiers: Invasive malignancy, CNS disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

184 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IPH6501 for individuals with B-cell non-Hodgkin's lymphoma. The goal is to determine the treatment's safety and identify the best dose for future studies. Participants should have this cancer, have tried at least two other treatments, and have no remaining treatment options. This trial may suit those whose cancer has returned or is not responding to current treatments. 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 it.

Will I have to stop taking my current medications?

The trial requires that you have not had chemotherapy, immunotherapy, or other anti-cancer treatments within 4 weeks before starting the study drug. It does not specify about other medications, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that IPH6501 is likely to be safe for humans?

Research shows that IPH6501 is under investigation for its safety and effectiveness in treating B-cell non-Hodgkin lymphoma. Although human trials have provided limited information so far, early lab and animal studies have shown promising results. These studies found that IPH6501 could effectively kill cancer cells and promote the growth of natural killer (NK) cells, which are part of the body's immune system.

Currently, researchers are testing IPH6501 in humans for the first time, so its safety profile in people is still being assessed. At this early stage, the main goal is to evaluate how well participants tolerate the treatment and identify any side effects. Because this is the first human trial of IPH6501, close monitoring of participants is crucial to ensure their safety and determine the best dose for future studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, which often include chemotherapy, radiation, and targeted therapies, IPH6501 represents a novel approach by targeting specific immune pathways. Researchers are excited about IPH6501 because it utilizes a new mechanism of action that potentially enhances the body's immune response against cancer cells. This could lead to more effective and less toxic treatment options, offering hope for improved outcomes and quality of life for patients with this type of lymphoma.

What evidence suggests that IPH6501 might be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that IPH6501, administered as monotherapy in this trial, might effectively treat non-Hodgkin's lymphoma. In lab tests, IPH6501 enabled immune cells from patients to destroy cancer cells, particularly when other treatments failed. This treatment activates NK cells, a type of immune cell, to attack and kill lymphoma cells. IPH6501 demonstrated significant activity in patient samples, suggesting it could reduce tumor size. It proved more effective than some similar treatments, highlighting its potential as a new approach to combat this cancer. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with advanced B-cell non-Hodgkin's lymphoma who have tried at least two treatments, including anti-CD20 antibody therapy. They should be in a condition to perform daily activities (ECOG ≤ 2) and have good organ function. A recent or historical biopsy is required. Those with other cancers within the last 2 years, recent cancer therapies, CNS issues, HIV/hepatitis infections, major surgery within the past month or pregnancy are excluded.

Inclusion Criteria

I can provide a new or past biopsy sample from a site that can be safely accessed.

I have a type of non-Hodgkin's lymphoma that tests positive for CD20.

My condition is worsening and there are no other treatment options for me.

Exclusion Criteria

I have a history of HIV or hepatitis B/C.

I have diabetes, heart disease, or an immune system condition.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 - Dose Finding

Dose escalation to determine the Maximum Tolerated Dose (MTD) and dose assessment to determine the recommended phase 2 dose (RP2D)

Variable duration

Phase 2 - Dose Expansion

One or more cohorts will be selected with patients with subtypes of advanced histologically confirmed, documented CD20+ B-cell non-Hodgkin lymphoma

Variable duration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 22 months

What Are the Treatments Tested in This Trial?

Interventions

• IPH6501

Trial Overview The study tests IPH6501 on people with relapsed/refractory B-cell non-Hodgkin lymphoma to assess safety and find the best dose for Phase 2 trials. It's an international study where everyone gets IPH6501; there are no comparison groups.

How Is the Trial Designed?

Group I: IPH6501 monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Innate Pharma

Lead Sponsor

Trials

29

Recruited

3,100+

Published Research Related to This Trial

In a trial involving 10 patients with high-grade non-Hodgkin's lymphoma, subcutaneous administration of recombinant interleukin 2 (rIL2) significantly increased the number and activity of natural killer (NK) cells, which are crucial for immune response, suggesting enhanced immune function post-treatment.

None of the patients relapsed during the study, and two patients with residual disease achieved complete remission after rIL2 therapy, indicating that rIL2 may have a beneficial effect on minimal residual disease following autologous bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low doses of rIL2 after autologous bone marrow transplantation induce a "prolonged" immunostimulation of NK compartment in high-grade non-Hodgkin's lymphomas. Raspadori, D., Lauria, F., Ventura, MA., et al.[2019]

IL-21 treatment preserves a crucial subset of central memory-like NKT cells (CD62L+) during expansion, enhancing their antitumor functionality against B cell lymphoma.

Combining IL-2 with IL-21 not only increases the number of NKT cells but also improves their survival and cytotoxicity, leading to significantly better outcomes in lymphoma-bearing mice compared to IL-2 alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-21 Selectively Protects CD62L+ NKT Cells and Enhances Their Effector Functions for Adoptive Immunotherapy. Ngai, H., Tian, G., Courtney, AN., et al.[2019]

This case report describes the first known instance of a hematological malignancy arising from helper innate lymphoid cells (ILCs) in a 17-year-old male, characterized by aggressive behavior and resistance to chemotherapy, leading to the patient's death within 6 months.

The tumor exhibited unique phenotypic markers associated with helper ILCs, such as CD127 and IL-1R, and showed significant genetic alterations, including a novel IGLV2-14/IGLL5 fusion, suggesting a distinct mechanism of tumorigenesis that expands the understanding of hematological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lineage-negative lymphoma with a helper innate lymphoid cell phenotype. Li, M., Su, X., Wang, Y., et al.[2020]

Immunotherapy has emerged as a promising treatment for natural killer/T-cell lymphoma (NKTCL), showing good clinical results with targeted antibodies like daratumumab and brentuximab vedotin, especially due to the high expression of programmed death-ligand 1 in NKTCL.

Cellular immunotherapy using engineered cytotoxic T lymphocytes targeting specific viral proteins has demonstrated potential for sustained remission, suggesting it could be effective as maintenance therapy after initial treatment or for relapsed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updating targets for natural killer/T-cell lymphoma immunotherapy. Xue, W., Zhang, M.[2021]

The development of membrane-bound IL-2 (mbIL-2) allows NK-92 cells to proliferate and survive without the need for external IL-2, which reduces the risk of systemic toxicity associated with traditional IL-2 administration.

mbIL-2 not only improves the persistence of NK-92 cells but also enhances their ability to attack tumors by optimizing signaling pathways and increasing the expression of important receptors, indicating its potential for clinical use in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel membrane-bound interleukin-2 promotes NK-92 cell persistence and anti-tumor activity. Xiong, Q., Zhang, H., Ji, X., et al.[2022]

In a study involving 20 patients with high-risk diffuse large B cell lymphoma (DLBCL), autologous cytokine-induced killer (CIK) cell immunotherapy significantly improved the 5-year disease-free survival (DFS) from 45.0% to 79.3% and the overall survival (OS) from 55% to 90%.

The treatment was found to be safe, with no severe side effects reported, and it effectively increased the proportions of key immune cells (CD3+ T cells, CD3+CD8+ T cells, and NK cells) in the patients' blood after transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Cytokine-Induced Killer Cell Immunotherapy for Patients with High-Risk Diffuse Large B Cell Lymphoma After the First Complete Remission. Zhou, M., Wang, J., Li, CP., et al.[2022]

High-dose interleukin-2 (IL-2) treatment has become less popular due to its severe and potentially life-threatening side effects.

A new method has been developed to specifically target IL-2 to cytotoxic lymphocytes, using a modified IL-2 that minimizes harmful effects on regulatory T cells and blood vessel cells, potentially improving safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of IL-2 to cytotoxic lymphocytes as an improved method of cytokine-driven immunotherapy. Lazear, E., Ghasemi, R., Hein, SM., et al.[2021]

In a study of 65 patients with NK/T cell lymphoma (NKTCL), serum levels of cytokines IL-17, IL-22, and IL-23 were significantly elevated compared to 60 healthy controls, indicating their potential role in the disease.

ROC curve analysis showed that IL-17 had a high diagnostic value for NKTCL with an AUC of 0.9487, suggesting it could be a reliable biomarker for early diagnosis, while IL-22 and IL-23 also showed promise but with lower AUC values.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic value of IL-22, IL-23, and IL-17 for NK/T cell lymphoma. Qi, Y., Liao, B., Chen, J., et al.[2023]

The engineered anti-CD20-interleukin 2 (IL-2) immunocytokine, DI-Leu16-IL-2, demonstrated superior effectiveness in treating lymphoma in SCID mice compared to traditional anti-CD20 antibodies, achieving significant tumor clearance at a much lower dose (0.25 mg/kg vs. 25 mg/kg).

DI-Leu16-IL-2 retained full anti-CD20 activity and enhanced antibody-dependent cellular cytotoxicity (ADCC), indicating that both ADCC and IL-2 targeting contribute to its antitumor effects, suggesting promising therapeutic potential for patients with CD20 positive lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-CD20-IL-2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma. Gillies, SD., Lan, Y., Williams, S., et al.[2021]

In a study of 90 allogeneic hematopoietic stem cell transplant recipients, low-dose interleukin-2 (IL-2) administration did not significantly reduce leukemia relapse rates but was associated with a higher rate of GVHD-free survival (47% vs. 31% in the control group).

Patients receiving IL-2 showed a lower incidence of moderate-to-severe chronic graft-versus-host disease (cGVHD) compared to the control group (33% vs. 57%), indicating that IL-2 may help mitigate this common post-transplant complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study. Zhao, XY., Zhao, XS., Wang, YT., et al.[2021]

Interleukin-2 (IL-2) can effectively stimulate immune responses in some cancer patients, particularly those with melanoma and renal cancer, but its use is limited by serious side effects and effectiveness in only a subset of patients.

Current research is focused on developing strategies to enhance the benefits of IL-2 therapy by minimizing side effects and preferentially activating effector T cells while reducing the activation of regulatory T cells, which suppress immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy. Skrombolas, D., Frelinger, JG.[2021]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can lead to long-term survival in about 48.6% of patients with relapsed/refractory natural killer/T-cell lymphomas (NKTCL), based on a study of 135 patients over a median follow-up of 4.8 years.

The timing of the transplant and the patient's condition at the time of transplantation significantly affect progression-free survival, with shorter intervals between diagnosis and transplant and not being in complete or partial remission associated with poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for NK/T-cell lymphoma: an international collaborative analysis. Berning, P., Schmitz, N., Ngoya, M., et al.[2023]

Citations

1. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A1203.info

a novel IL2v-armed tetraspecific NK cell engager targeting ... In vitro, cytotoxicity assays reveal that IPH6501 stimulates PBMCs from post rituximab R/R B-NHL patients to kill a CD20+ lymphoma cell line.

2. innate-pharma.com innate-pharma.com/media/all-press-releases/innate-pharma-highlights-preclinical-antitumor-activity-iph6501-diffuse-large-b-cell-lymphoma-and-follicular-lymphoma-2025-european-hematology-association-eha-congress

Innate Pharma highlights preclinical antitumor activity of ... IPH6501 demonstrated potent NK cell proliferation and tumor cell killing activity in DLBCL and FL patient samples, supporting its therapeutic potential in ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39546590/

A tetraspecific engager armed with a non-alpha IL-2 variant ... We evaluated IPH6501, a clinical-stage, tetraspecific NK cell engager (NKCE) armed with a non-alpha IL-2 variant (IL-2v), which targets CD20 and ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS7095

A phase 1/2, open-label, multicenter trial investigating the ... In samples obtained from R/R B-NHL patients, IPH6501 demonstrated greater killing efficacy compared to a CD3xCD20 T-cell engager, and yet lower ...

5. science.org science.org/doi/10.1126/sciimmunol.adp3720

A tetraspecific engager armed with a non-alpha IL-2 ... We evaluated IPH6501, a clinical-stage, tetraspecific NK cell engager (NKCE) armed with a non-alpha IL-2 variant (IL-2v), which targets CD20 and ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5824/526764/Preclinical-Characterization-of-Antitumor-Activity

Preclinical Characterization of Antitumor Activity of IPH6501, a ... IPH6501 is therefore a promising first-in-class NK cell engager candidate for the treatment of B-NHL. Its safety and preliminary efficacy are ...

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-iph6501-for-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma/

Study on the Safety and Effects of IPH6501 for Patients ... This clinical trial examines the safety and effects of IPH6501, an infusion treatment, for patients with relapsed or refractory Non-Hodgkin Lymphoma, ...