IPH6501 for Non-Hodgkin's Lymphoma

Recruiting at 13 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

Trial Summary

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.

What data supports the effectiveness of the treatment IPH6501, CD20-NKCE-IL2v, for Non-Hodgkin's Lymphoma?

Research shows that interleukin-2 (IL-2), a component of the treatment, can boost the activity and number of natural killer (NK) cells, which are important for fighting cancer. Additionally, a similar treatment combining anti-CD20 and IL-2 was highly effective in a mouse model of lymphoma, suggesting potential benefits for patients with CD20 positive lymphoma. ^{1 2 3 4 5}

What safety data exists for IPH6501 (CD20-NKCE-IL2v) treatment in humans?

Research on treatments similar to IPH6501, like IL-2, shows that while they can boost immune cell activity, they may also cause serious side effects. Efforts are being made to reduce these side effects by targeting the treatment more precisely to immune cells. ^{1 2 3 6 7}

What makes the drug IPH6501 unique for treating Non-Hodgkin's Lymphoma?

IPH6501 is unique because it combines a CD20-targeting component with an engineered version of IL-2, which may enhance the immune system's ability to attack lymphoma cells more effectively than traditional treatments. ^{8 9 10 11 12}

What is the purpose of this trial?

This is an international, first-in-human, multicenter, open-label Phase 1/2 study to evaluate the safety profile, tolerability of IPH6501, and determine the recommended phase 2 dose (RP2D) for patients with B-Cell non-Hodgkin lymphoma.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: IPH6501 monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Innate Pharma

Lead Sponsor

Trials

29

Recruited

3,100+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Germany 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. [2019]

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

A novel membrane-bound interleukin-2 promotes NK-92 cell persistence and anti-tumor activity. [2022]

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

An anti-CD20-IL-2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma. [2021]

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

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study. [2021]

5. New Zealand 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Targeting of IL-2 to cytotoxic lymphocytes as an improved method of cytokine-driven immunotherapy. [2021]

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

IL-21 Selectively Protects CD62L+ NKT Cells and Enhances Their Effector Functions for Adoptive Immunotherapy. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Lineage-negative lymphoma with a helper innate lymphoid cell phenotype. [2020]

10. China pubmed.ncbi.nlm.nih.gov

Updating targets for natural killer/T-cell lymphoma immunotherapy. [2021]

11. France pubmed.ncbi.nlm.nih.gov

Diagnostic value of IL-22, IL-23, and IL-17 for NK/T cell lymphoma. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for NK/T-cell lymphoma: an international collaborative analysis. [2023]