ONO-4685 for Lymphoma

Recruiting at 16 trial locations

Overseen By International Clinical Trial Support Desk

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ono Pharmaceutical Co. Ltd

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: CNS involvement, ATLL, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

217 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ONO-4685 to determine its safety and effectiveness for people with a specific type of blood cancer known as T cell lymphoma. It targets individuals whose cancer has returned or has not responded to at least two other treatments. Ideal participants have specific types of T cell lymphoma, such as peripheral T-cell lymphoma or advanced cutaneous T-cell lymphoma, with noticeable signs of the disease. The study aims to help researchers understand how the body processes ONO-4685 and its potential effects on cancer. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ONO-4685 is likely to be safe for humans?

Research has shown that ONO-4685 is being tested for safety and tolerability. This treatment targets individuals with T-cell lymphoma that has returned or is unresponsive to other treatments. As ONO-4685 is in the early testing stages, limited information exists about its safety in humans.

Researchers are examining how the body reacts to different doses of ONO-4685 and monitoring for side effects. This new treatment aids the immune system in attacking cancer cells, making safety understanding crucial.

Currently, specific information about side effects or tolerability is unavailable. The trial aims to gather this data. Prospective participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Lymphoma?

ONO-4685 is unique because it targets T cell lymphoma, a challenging condition where standard treatments like chemotherapy and radiation often struggle to provide lasting solutions. Unlike these conventional options, ONO-4685 is a monotherapy that specifically focuses on the cancerous T cells, potentially offering a more targeted approach with fewer side effects. Researchers are excited about this treatment because its novel mechanism of action could lead to more effective and durable responses in patients who have not had success with existing therapies.

What evidence suggests that ONO-4685 might be an effective treatment for T cell Lymphoma?

Research has shown that ONO-4685, the investigational treatment in this trial, might help treat T cell lymphoma by boosting the body's immune system. This treatment targets specific proteins on cancer cells, potentially aiding the immune system in identifying and destroying them more effectively. Early laboratory studies demonstrated that ONO-4685 can slow tumor growth, with higher doses having a stronger effect. These initial results suggest that ONO-4685 could benefit patients whose T cell lymphoma has returned or not responded to other treatments, but further research is needed to confirm these findings. ^{1 4 6 7 8}

Who Is on the Research Team?

Project Leader

Principal Investigator

Ono Pharmaceutical Co. Ltd

Are You a Good Fit for This Trial?

Adults over 18 with relapsed or refractory T cell lymphoma, who've had at least two prior treatments and have measurable disease, can join this trial. They must not be pregnant, have a central nervous system involvement, HIV, hepatitis B or C infections, recent tuberculosis infection, severe allergies to monoclonal antibodies or corticosteroids.

Inclusion Criteria

Life expectancy of at least 3 months

I have PTCL with at least one tumor that can be measured.

My diagnosis is a specific type of T-cell lymphoma.

Exclusion Criteria

I do not have an active infection like HIV or hepatitis B/C.

I have a cancer type other than T-cell lymphoma.

I still have side effects from previous cancer treatments that haven't improved.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ONO-4685 monotherapy to assess safety, tolerability, and preliminary efficacy

3 weeks

Weekly visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Regular visits for pharmacokinetics and immunogenicity assessments

Long-term follow-up

Participants are monitored for long-term safety and antitumor activity

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• ONO-4685

Trial Overview The trial is testing ONO-4685's safety and effectiveness for patients with specific types of T cell lymphoma that haven't responded well to previous treatments. It will look at how the body processes the drug and its preliminary success in treating the cancer.

How Is the Trial Designed?

Group I: ONO-4685 monotherapy Experimental Treatment 1 Intervention

Patients with relapsed or refractory T cell Lymphoma who meet eligibility criteria will be enrolled to receive ONO-4685 monotherapy

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 49 dogs with intermediate- and high-grade peripheral nodal T-cell lymphoma, L-CHOP chemotherapy resulted in a high overall response rate of 98%, indicating that this treatment is effective for this type of cancer.

However, the median progression-free survival (PFS) was relatively short, with 103 days for the placebo group compared to 64 days for the group receiving the monoclonal antibody AT-005, suggesting that while the treatment is effective, it may not significantly prolong survival time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised trial evaluating chemotherapy alone or chemotherapy and a novel monoclonal antibody for canine T-cell lymphoma: A multicentre US study. Musser, ML., Clifford, CA., Bergman, PJ., et al.[2022]

In a study involving 40 dogs with peripheral nodal lymphoma, those treated with the full L-CHOP chemotherapy protocol (including prednisone) had a median progression-free survival time of 292 days, compared to 142.5 days for those who received the L-CHO protocol without prednisone.

The trial found that omitting prednisone did not improve progression-free survival, and while serious adverse events were more common in the L-CHO group, the difference was not statistically significant, suggesting that the study may not have been large enough to detect meaningful differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of the effect of prednisone omission from a multidrug chemotherapy protocol on treatment outcome in dogs with peripheral nodal lymphomas. Childress, MO., Ramos-Vara, JA., Ruple, A.[2017]

Paclitaxel and docetaxel, both derived from the yew tree, have shown significant antitumor activity in non-Hodgkin's lymphoma, with response rates of 30% CR and 14% PR for paclitaxel, and up to 29.4% response rate for docetaxel in various studies involving relapsed lymphomas.

Rituximab, a monoclonal antibody targeting CD20, demonstrated a 46% response rate in patients with relapsed low-grade lymphoma, and when combined with CHOP chemotherapy, it resulted in complete or partial responses in all newly diagnosed patients, indicating its potential effectiveness in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New antitumor drugs for non-Hodgkin's lymphoma]. Ohnishi, K., Ohno, R.[2018]

Complete remission rates for adult patients with high-grade non-Hodgkin's lymphoma range from 50% to 80%, with average disease-free survival rates of 40-50% at 3 years and 30-35% at 5 years, indicating a significant potential for successful treatment.

CHOP chemotherapy remains the standard treatment, but aggressive regimens and dose intensification have not shown improved overall survival, suggesting that supportive therapies like cytokines may be necessary to maintain full-dose treatment schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of high-grade non-Hodgkin's lymphoma]. Jäger, U., Karth, GD., Knapp, S., et al.[2015]

Combination chemotherapy with CHOP (cyclophosphamide, hydroxydaunorubin, vincristine, and prednisone) is the first-line treatment for high-grade non-Hodgkin's lymphomas, achieving long-term remission or potential cure in 30-50% of advanced cases.

For low-grade lymphomas, a watch-and-wait approach is often used until treatment is necessary, with moderate-intensity chemotherapy options available, and new therapies like maintenance with interferon-alpha and innovative agents like purine analogues showing promise for improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Hodgkin's lymphomas--current status of therapy and future perspectives. Hiddemann, W.[2019]

Citations

1. medicine.yale.edu medicine.yale.edu/ycci/clinicaltrials/trial/ono-4685-03-study-of-ono-4685-in-patients-with-relapsed-or-refractory-t-cell-lymphoma/

Study of ONO-4685 in Patients With Relapsed or Refractory T ... This study will investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ONO-4685 in patients with relapsed or refractory T cell.

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/7324/759925/Abstract-7324-ONO-4685-A-novel-PD-1-CD3-bispecific

Abstract 7324: ONO-4685: A novel PD-1/CD3 bispecific T-cell ... ONO-4685 treatment showed suppressive effects on tumor growth in a dose-dependent manner.Taken together, these preclinical data support the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05079282

NCT05079282 | Study of ONO-4685 in Patients With ... This study will investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ONO-4685 in patients with relapsed or refractory T cell ...

4. clfoundation.org clfoundation.org/study-ono-4685-patients-relapsed-or-refractory-t-cell-lymphoma-0

Study of ONO-4685 in Patients With Relapsed or ... The primary objective of this Phase I study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ONO-4685 given as monotherapy ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/22-045

A Phase I Study of ONO-4685 Immunotherapy in People ... ONO-4685 may strengthen the immune system's ability to fight cancer cells by activating a patient's own cells to destroy the tumor. It is given intravenously ( ...

6. clfoundation.org clfoundation.org/ono-4685-clinical-trial

ONO-4685 Clinical Trial This study is a multicenter, open label, dose escalation Phase 1 study to evaluate ONO-4685 in patients with relapsed or refractory T-cell lymphoma.

7. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/open-label-multi-center-non-randomized-phase-i-dose-escalation-study-investigate-safety-tolerability-pharmacokinetics-and-preliminary-efficacy-ono-4685-given-monotherapy-patients-relapsed-or-refractory

An open-label, multi-center, non-randomized phase I dose ... The purpose of this study is to find out the safety, effectiveness, and blood levels of various doses of the study drug in participants with T-cell lymphoma.

8. ucihealth.org ucihealth.org/clinical-trials/uci-21-99

Study Description ... Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ONO-4685 Given as Monotherapy in Patients with Relapsed or Refractory T-Cell Lymphoma. UCI ...