ONO-7018 for Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia

Not currently recruiting at 11 trial locations

Overseen By Ono Pharma USA, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ono Pharmaceutical Co. Ltd

Must not be taking: MALT1 inhibitors, Investigational drugs

Disqualifiers: CNS involvement, Active infection, others

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

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 ONO-7018 for certain blood cancers, such as Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia. The goal is to determine the safety and effectiveness of ONO-7018 by starting with small doses and gradually increasing them to find the optimal amount. The trial seeks participants with these specific cancers, particularly those for whom other treatments have failed and who have measurable signs of the disease. 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.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken another investigational drug within 4 weeks before the study starts.

Do I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken another investigational drug within 4 weeks before the study.

Is there any evidence suggesting that ONO-7018 is likely to be safe for humans?

Research shows that ONO-7018 is undergoing testing for certain blood cancers, such as non-Hodgkin's lymphoma and chronic B-cell leukemia. This new drug is in its first phase of human testing, marking its initial administration to people to assess safety.

As a Phase 1 trial, the primary goal is to determine ONO-7018's safety and establish the optimal dose. At this stage, information about drug tolerance and potential side effects remains limited. However, earlier lab and animal studies suggested that ONO-7018 might be effective against certain blood cancers.

Participants in this study will help researchers gather more information about the possible side effects and safety of ONO-7018 in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ONO-7018 for treating Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia because it offers a fresh approach compared to traditional therapies like chemotherapy and immunotherapy. ONO-7018 is unique because it targets specific pathways within cancer cells, potentially leading to more precise and effective treatment with fewer side effects. This targeted mechanism may allow ONO-7018 to overcome resistance that some patients experience with current standard treatments, providing a promising new option for those who don't respond well to existing therapies.

What evidence suggests that ONO-7018 might be an effective treatment for Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia?

Research shows that ONO-7018 could be a promising treatment for Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia. It blocks a protein called MALT1, which aids cancer cell growth. Lab studies have demonstrated that ONO-7018 effectively stops the growth of lymphoma cells. Although these results are encouraging, the treatment remains in the early testing stages, and specific data on its effectiveness in people with these conditions is not yet available. However, the success in lab models offers hope for its potential effectiveness in patients. Participants in this trial will receive different dose levels in the Dose Escalation Phase or the recommended dose level in the Dose Expansion Phase to further evaluate its effectiveness and safety. ^{1 2 4 5 6}

Who Is on the Research Team?

Project Leader

Principal Investigator

Ono Pharma USA Inc

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain types of blood cancers (NHL or CLL) that have come back or haven't responded to treatment, and who don't have other good treatment options. They should be fairly active (ECOG 0-2), able to swallow tablets, and not have serious medical issues that could affect the study.

Inclusion Criteria

All side effects from my previous cancer treatments are mild now.

Written informed consent by the patient or the patient's legally authorized representative

I can take care of myself and perform daily activities.

Exclusion Criteria

Patient is found to be otherwise ineligible for the study by the investigator or sub investigator

Patient receiving any other investigational drug within 4 weeks prior to study entry

I currently have an active, body-wide infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Phase (Part 1)

Up to 4 dose levels will be evaluated using a traditional 3+3 dose escalation design

Up to 3 weeks

Dose Expansion Phase (Part 2)

Eligible patients will be assigned to the recommended dose level(s) selected from Part 1

Up to 48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ONO-7018

Trial Overview ONO-7018 is being tested in this first-in-human study which has two parts: finding the right dose and then seeing how well it works at that dose. It's an open-label study, meaning everyone knows they're getting ONO-7018, and it's given across multiple centers.

How Is the Trial Designed?

Group I: Dose Expansion Phase (Part 2) Experimental Treatment 1 Intervention

Eligible patients will be assigned to the recommended dose level(s) selected from Part 1.

Group II: Dose Escalation Phase (Part 1) Experimental Treatment 1 Intervention

Up to 4 dose levels will be evaluated. Eligible patients will be assigned to a dose level cohort according to a traditional 3+3 dose escalation design.

Who Is Running the Clinical Trial?

Ono Pharmaceutical Co. Ltd

Lead Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Published Research Related to This Trial

In a study of 28 patients with non-Hodgkin's lymphoma treated with 90Y-ibritumomab, 22 patients showed objective responses, indicating that this radioimmunotherapy is effective for managing NHL.

Patients with negative findings from the diagnostic 111In-ibritumomab scans had a higher rate of complete response to treatment, suggesting that those with bulky disease may need more aggressive management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

90Y-ibritumomab therapy in refractory non-Hodgkin's lymphoma: observations from 111In-ibritumomab pretreatment imaging. Iagaru, A., Gambhir, SS., Goris, ML.[2016]

PD-1 blockade has shown high efficacy in treating relapsed/refractory classical Hodgkin lymphoma, with objective response rates (ORRs) between 65% to 87% and a median duration of response of 16 months in clinical trials.

While PD-1 blockade is effective in certain B-cell lymphomas, such as primary mediastinal large B-cell lymphoma (ORR of 35%), it has limited efficacy in others like chronic lymphocytic leukemia (0% ORR), highlighting the importance of tumor-specific characteristics in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Xu-Monette, ZY., Zhou, J., Young, KH.[2022]

Rituximab, an anti-CD20 monoclonal antibody, has demonstrated effectiveness and acceptable safety in treating both indolent and aggressive B-cell non-Hodgkin's lymphomas, particularly when combined with CHOP chemotherapy, leading to improved survival rates in elderly patients.

Radioimmunotherapy using (90)Y-ibritumomab tiuxetan has shown a higher response rate than rituximab in relapsed indolent B-NHL, indicating that targeted radiation therapy can be a promising approach in treating lymphoid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab and other emerging antibodies as molecular target-based therapy of lymphoma. Tobinai, K.[2015]

90Y ibritumomab tiuxetan, a targeted radiation therapy, has shown efficacy in treating B-cell non-Hodgkin's lymphoma (NHL), with established therapeutic doses of 0.4 mCi/kg for low-grade NHL patients.

Ongoing trials are exploring various dosing schedules and combinations with chemotherapy and stem cell transplantation to enhance treatment response and duration, indicating the potential for improved survival rates in NHL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibritumomab tiuxetan for non-Hodgkin's lymphoma. Johnston, PB., Bondly, C., Micallef, IN.[2016]

In a study using Monte Carlo-based dosimetry, (131)I-labeled antibodies showed greater therapeutic efficacy than (90)Y-labeled antibodies for treating smaller lung metastases (less than 2.0 cm) in non-Hodgkin's lymphoma patients.

Both (90)Y and (131)I targeting were found to be more effective at lower tumor burdens, with (131)I consistently providing a better therapeutic ratio, especially beneficial for smaller tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of 90Y- and 131I-labeled anti-CD20 monoclonal antibody in treating non-Hodgkin's lymphoma with pulmonary involvement: a Monte Carlo-based dosimetric analysis. Song, H., Du, Y., Sgouros, G., et al.[2018]

The article corrected a significant error regarding ONO/GS-4059, clarifying that it is an 'irreversible' inhibitor of Bruton's tyrosine kinase (BTK), contrary to its previous description as 'reversible'.

This correction is important for accurately understanding the mechanism of action of ONO/GS-4059 in the treatment of chronic lymphocytic leukemia and lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction: Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia and lymphoma. [2019]

The combination of idelalisib and ONO/GS-4059 showed significant tumor regression in a mouse model of activated B-cell-like diffuse large B-cell lymphoma, indicating enhanced efficacy through complementary mechanisms of action.

Resistance mechanisms to idelalisib were identified, including mutations and pathway upregulation, but sensitivity could be restored by combining it with ONO/GS-4059, suggesting a promising new therapeutic strategy for overcoming resistance in this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors. Yahiaoui, A., Meadows, SA., Sorensen, RA., et al.[2022]

Ibrutinib significantly improves progression-free survival (PFS) in patients with chronic lymphocytic leukemia (CLL), with a long-term follow-up showing a hazard ratio of 0.133, indicating a strong benefit over ofatumumab.

The overall response rate to ibrutinib increased over time, reaching 91%, and while grade ≥3 adverse events decreased, 27% of patients discontinued treatment due to disease progression, highlighting both the efficacy and manageable safety profile of ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. Byrd, JC., Hillmen, P., O'Brien, S., et al.[2022]

In a phase 2 study involving 25 patients with relapsed chronic lymphocytic leukemia (CLL) and Richter transformation (RT), pembrolizumab showed a 44% objective response rate in RT patients who had previously progressed on ibrutinib, indicating its potential efficacy in this difficult-to-treat population.

Despite manageable treatment-related adverse events in 60% of patients, the study found that pembrolizumab may improve overall survival in RT patients, with a median survival of 10.7 months, suggesting a promising new therapeutic option for those with RT following ibrutinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Ding, W., LaPlant, BR., Call, TG., et al.[2022]

Nivolumab significantly improves long-term overall survival in patients with advanced squamous and non-squamous non-small cell lung cancer (NSCLC), with median survival times of 16.3 months for squamous and 17.1 months for non-squamous patients, and 3-year survival rates of 20.0% and 31.9%, respectively.

The treatment was well tolerated, with no new safety concerns identified, indicating that nivolumab is a safe and effective option for patients who have previously been treated for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year follow-up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non-small cell lung cancer: Pooled analysis of ONO-4538-05 and ONO-4538-06 studies. Horinouchi, H., Nishio, M., Hida, T., et al.[2021]

Monoclonal antibodies like rituximab are becoming established treatments for Non-Hodgkin lymphoma (NHL), especially in elderly patients, due to their lower toxicity compared to conventional chemotherapy.

Emerging therapies, including combinations of monoclonal antibodies with radiotherapy (radio-immunotherapies), show promising results for treating advanced indolent lymphomas and are being explored for use in high-grade lymphomas and as first-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Innovative antibody-therapies for malignant lymphomas]. Müller, AM., Rawluk, J., Thierry, V., et al.[2017]

In a phase 1 study involving 90 patients with relapsed/refractory B-cell malignancies, the selective BTK inhibitor ONO/GS-4059 showed a high response rate, with 96% of chronic lymphocytic leukemia (CLL) patients responding and a median treatment duration of 80 weeks.

ONO/GS-4059 was well tolerated, with 75% of adverse events being mild (grade 1 or 2), and no significant severe toxicities were observed, indicating its potential for safe use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Walter, HS., Rule, SA., Dyer, MJ., et al.[2021]

The BTK inhibitor ONO/GS-4059 shows significant anti-tumor activity when combined with anti-CD20 antibodies, achieving tumor growth inhibition of 90% with obinutuzumab (GA101) and 86% with rituximab (RTX) in treating activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL).

In contrast, the combination of ibrutinib with rituximab did not enhance efficacy compared to monotherapy, suggesting that ONO/GS-4059 may be a more effective option for this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab. Yasuhiro, T., Sawada, W., Klein, C., et al.[2020]

Nivolumab treatment for up to 5 years showed promising long-term survival rates in patients with advanced non-small cell lung cancer, with a median overall survival of 17.1 months and a 5-year survival rate of 17.8%.

The study found that higher levels of programmed death ligand-1 expression were associated with better survival outcomes, indicating that this biomarker may help predict patient response to nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year follow-up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non-small cell lung cancer: pooled analysis of the ONO-4538-05 and ONO-4538-06 studies. Saka, H., Nishio, M., Hida, T., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS7083

A phase I, first-in-human study of ONO-7018 in patients ... ONO-7018 is an oral, potent, and selective MALT1 inhibitor that has demonstrated preclinical efficacy in several lymphoma models (Morishita D, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123123792

ONO-7018, a First-in-Class MALT1 Inhibitor, Provides ... ONO-7018 (formerly known as CTX-177), a potent and selective MALT1 inhibitor, demonstrated preclinical efficacy in several lymphoma models.

3. withpower.com withpower.com/trial/phase-1-lymphoma-non-hodgkin-2023-34a4d

ONO-7018 for Non-Hodgkin's Lymphoma and Chronic B- ... The available research does not provide specific data on the effectiveness of ONO-7018 for Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia. Instead, it ...

4. researchgate.net researchgate.net/publication/381340177_A_phase_I_first-in-human_study_of_ONO-7018_in_patients_with_relapsedrefractory_non-Hodgkin_lymphoma_or_chronic_lymphocytic_leukemia

A phase I, first-in-human study of ONO-7018 in patients ... ONO-7018 is an oral, potent, and selective MALT1 inhibitor that has demonstrated preclinical efficacy in several lymphoma models (Morishita D, et al. Blood.

5. us.ono-pharma.com us.ono-pharma.com/news/phase-1-study-ono-7018

Phase 1 Study of ONO-7018 MALT1 Inhibitor This study is a multicenter, open label, dose escalation Phase 1 study (ONO-7018-01) to evaluate ONO-7018 in patients with relapsed or refractory NHL or CLL.

6. ctv.veeva.com ctv.veeva.com/study/a-study-to-investigate-the-safety-tolerability-pk-pd-and-efficacy-of-ono-7018-in-patients-with-r

A Study to Investigate the Safety, Tolerability, PK, PD, and ... ONO-7018 is a selective inhibitor of mucosa associated lymphoid tissue protein 1 (MALT1) and is expected to exhibit antitumor activity in NHL ...