ONO-4578 + Opdivo for Colorectal Cancer

Recruiting at 11 trial locations

Overseen By International Clinical Trial Support Desk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ono Pharmaceutical Co. Ltd

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

Disqualifiers: MSI-High, BRAF V600E, autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 39 months

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of ONO-4578 (an experimental treatment) and Opdivo (an immunotherapy drug) when combined with standard chemotherapy for advanced colorectal cancer. Participants are divided into groups: two groups receive different doses of ONO-4578 with Opdivo, while one group receives only the standard chemotherapy. The trial targets individuals whose colorectal cancer has spread, cannot be surgically removed, have not received prior treatment for advanced cancer, and have tumors testing positive for the PD-L1 marker. Those meeting these criteria and who have not previously tried certain immunotherapies may find this trial suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 this trial's treatments are likely to be safe?

Research has shown that the combination of ONO-4578 and Opdivo is generally well-tolerated. One study found that this treatment has a manageable safety profile, with most side effects being mild to moderate. Patients experienced side effects similar to those expected with cancer treatments.

Additionally, previous patients taking ONO-4578 with Opdivo demonstrated promising safety and effectiveness. These findings suggest the treatment is safe for human use, as many patients have taken it without serious safety concerns.

Opdivo's approval for other cancers further supports its safety. Overall, existing research indicates that the treatment is tolerable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ONO-4578 combined with Opdivo for colorectal cancer because this combo aims to boost the body's immune system in a unique way. While traditional treatments like mFOLFOX6 and bevacizumab target the cancer cells directly, ONO-4578 may enhance the immune response, potentially making Opdivo more effective. This could offer a powerful new option for patients, especially if it shows better results in shrinking tumors or prolonging survival compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

This trial will evaluate the combination of ONO-4578 with Opdivo for colorectal cancer. Research has shown that combining ONO-4578 with Opdivo may help treat certain cancers. In earlier studies, this combination significantly increased progression-free survival, the time patients lived without their cancer worsening. Specifically, one study found that this period lasted a median of 12.3 months. The treatment also achieved a 73.5% success rate in shrinking tumors, with many patients experiencing partial shrinkage. These results suggest that this treatment could be effective for advanced colorectal cancer, offering hope for better outcomes. Participants in this trial will receive either ONO-4578 with Opdivo and standard of care (SOC) or SOC alone. ^{1 2 3 4 5}

Who Is on the Research Team?

Project Leader

Principal Investigator

Ono Pharmaceutical Co. Ltd

Are You a Good Fit for This Trial?

This trial is for adults with advanced colorectal cancer that can't be removed by surgery. They should have a good performance status, meaning they're able to carry out daily activities with minimal assistance. No previous systemic treatments for their condition are allowed, and their tumors must test positive for PD-L1.

Inclusion Criteria

My colorectal cancer is advanced and cannot be removed by surgery.

I am fully active or can carry out light work.

My tumor is PD-L1 positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ONO-4578 with Opdivo® in combination with mFOLFOX6 and bevacizumab or standard of care in 28-day cycles

Up to 39 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ONO-4578
• Opdivo

Trial Overview

The study tests two dose levels of ONO-4578 combined with Opdivo®, mFOLFOX6 (a chemo regimen), and Bevacizumab against the standard treatment. It aims to see if this combination is safe and works better for first-line treatment in advanced colorectal cancer.

How Is the Trial Designed?

Group I: Arm B ONO-4578 dose 2 + Opdivo® + SOC (mFOLFOX6 + bevacizumab) Experimental Treatment 6 Interventions

Group II: Arm A ONO-4578 dose 1 + Opdivo® + SOC (mFOLFOX6 + bevacizumab) Experimental Treatment 6 Interventions

Group III: Arm C SOC (mFOLFOX6+bevacizumab) Active Control 4 Interventions

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

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.93

Safety and efficacy of ONO-4578 plus nivolumab in ...

The primary endpoint was safety. Exploratory endpoints included efficacy and biomarkers. Results: A total of 51 patients were enrolled: 24 (47.1 ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06948448

NCT06948448 | A Study to Evaluate the Safety and ...

The purpose of this study is to evaluate the safety and efficacy of two dose levels of ONO-4578 with Opdivo® when added to mFOLFOX6 and bevacizumab versus SOC ...

3.

targetedonc.com

targetedonc.com/view/study-shows-promise-for-ono-4578-and-nivolumab-combo-in-gastric-cancer

Study Shows Promise for ONO-4578 and Nivolumab ...

A phase 2 trial reveals that ONO-4578 and nivolumab significantly extend progression-free survival in advanced gastric cancer patients.

4.

ono-pharma.com

ono-pharma.com/en/news/20251009_2.html

Ono Announces ONO-4578 (EP4 antagonist ...

In the trial, ONO-4578 in combination with Opdivo and chemotherapy demonstrated a statistically significant prolongation of progression-free ...

5.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)00205-9/fulltext

55P Safety, efficacy, and biomarkers of ONO-4578, an EP4 ...

The objective response rate (ORR) was 73.5% (partial response, 25 patients) and the median progression-free survival (PFS) was 12.3 months (95% CI, 7.0–17.1).