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

Recruiting in Palo Alto (17 mi)

+11 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Ono Pharmaceutical Co. Ltd

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing ONO-7018, a new drug designed to treat certain blood cancers that have not responded to other treatments. It works by blocking a protein that cancer cells need to grow. The study aims to find the best dose and check the drug's safety and effectiveness.

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.

What data supports the idea that ONO-7018 for Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia is an effective treatment?

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 discusses other treatments like nivolumab and pembrolizumab for different conditions, such as lung cancer and certain types of lymphomas. For example, pembrolizumab showed some effectiveness in patients with a specific transformation of chronic lymphocytic leukemia, but not in relapsed cases. Without direct data on ONO-7018, we cannot conclude its effectiveness for these conditions based on the provided information. ^{1 2 3 4 5}

What safety data is available for ONO-7018 in treating Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia?

The safety data for ONO-7018, also known as ONO/GS-4059, indicates that it is well tolerated in patients with relapsed/refractory B-cell malignancies. In a phase 1 trial, 75% of adverse events were mild to moderate (grade 1 or 2), and grade 3/4 adverse events were mainly hematologic and resolved spontaneously. One patient experienced a grade 3 bleeding event, but no significant diarrhea, cardiac dysrhythmias, or arthralgia were observed. The maximum tolerated dose was not reached in the CLL cohort, but was determined to be 480 mg once daily in the non-Hodgkin lymphoma cohort. Overall, ONO-7018 shows significant activity without major drug-related toxicity. ^{6 7 8 9 10}

Is the drug ONO-7018 a promising treatment for Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia?

The drug ONO-7018, also known as CTX-177, shows promise as a treatment for Non-Hodgkin's Lymphoma and Chronic B-Cell Leukemia. It is part of a new wave of therapies that target specific proteins on cancer cells, potentially leading to better outcomes for patients. Similar treatments have shown significant effectiveness in clinical trials, suggesting that ONO-7018 could be a valuable option in the fight against these types of cancers. ^{5 11 12 13 14}

Research Team

Project Leader

Principal Investigator

Ono Pharma USA Inc

Eligibility Criteria

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

I am 18 years old or older.

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

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

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.

Treatment Details

Interventions

• ONO-7018 (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. [2022]

2. United States 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. [2021]

3. England 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. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

[Innovative antibody-therapies for malignant lymphomas]. [2017]

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

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. [2022]

6. United States 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. [2021]

7. United States 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. [2020]

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

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

9. United States 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. [2022]

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

Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. [2022]

11. United States 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. [2018]

12. Japan pubmed.ncbi.nlm.nih.gov

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

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

90Y-ibritumomab therapy in refractory non-Hodgkin's lymphoma: observations from 111In-ibritumomab pretreatment imaging. [2016]

14. England pubmed.ncbi.nlm.nih.gov

Ibritumomab tiuxetan for non-Hodgkin's lymphoma. [2016]