What side effects are associated with this type of intervention?

BET bromodomain inhibitors like ZEN-3694 can cause side effects such as fatigue, nausea, and low blood cell counts. Nivolumab, a PD-1 inhibitor, is associated with immune-related side effects including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Ipilimumab, a CTLA-4 inhibitor, can cause similar immune-related side effects, with gastrointestinal toxicity being particularly common. Both Nivolumab and Ipilimumab can lead to severe immune-related adverse events requiring careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several drugs for cancer treatment that are similar to those being studied in the trial involving ZEN-3694, nivolumab, and ipilimumab. Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for various cancers, including melanoma, non-small cell lung cancer, and renal cell carcinoma. These drugs work by blocking proteins that inhibit the immune system from attacking cancer cells. Additionally, pembrolizumab, another immune checkpoint inhibitor, has been approved for similar indications. While specific FDA approvals for BET bromodomain inhibitors like ZEN-3694 are not detailed, the focus on blocking enzymes needed for cell growth is a common strategy in targeted cancer therapies.

What other types of research exist?

Promising novel alternatives for cancer treatment in 2024 include: 1) Manganese (Mn2+) combined with anti-PD-1 antibodies, which has shown synergistic antitumor effects and reduced dosage requirements in clinical trials. 2) Pembrolizumab combined with chemotherapy, which has demonstrated higher response rates and progression-free survival in patients with high PD-L1 expression. 3) Combination therapies involving other immune checkpoint inhibitors like Atezolizumab plus Bevacizumab, which have shown efficacy in various cancers such as renal cell carcinoma.

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Checkpoint Inhibitor

ZEN003694 + Nivolumab/Ipilimumab for Cancer

Phase 1

Recruiting

Led By Haider S Mahdi

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)

Creatinine clearance (CrCl) >= 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)

Must not have

Bowel obstruction or any condition precluding oral intake

Prior therapy with PD-1, PD-L1, or CTLA-4 inhibitors, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year post-treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug combination to treat solid tumors, especially in patients whose cancer doesn't respond to usual treatments. The drugs work by blocking tumor growth and boosting the immune system to fight the cancer. The goal is to find the best dose and see if the treatment can shrink or stabilize the tumors.

Who is the study for?

Adults with advanced solid tumors that have not responded to standard treatments may join this trial. They should have a good performance status, adequate organ function, and measurable disease that can be biopsied. Excluded are those with certain allergies, uncontrolled illnesses, severe heart conditions, active infections like HIV or hepatitis, recent immunosuppressive treatment, prior therapy targeting immune checkpoints or pregnant/breastfeeding women.

What is being tested?

The trial is testing the combination of ZEN003694 (a drug blocking enzymes for cell growth) with Nivolumab and possibly Ipilimumab (both boost the immune system to fight cancer). It aims to determine the best dose and assess potential benefits or side effects in shrinking or stabilizing solid tumors.

What are the potential side effects?

Possible side effects include allergic reactions similar to other monoclonal antibodies; issues related to immune system activation such as inflammation in organs; digestive problems; increased risk of infection due to immunotherapy drugs; and general symptoms like fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active and can carry on all pre-disease activities without restriction.

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My kidneys work well, with a creatinine clearance rate of 60 mL/min or higher.

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My cancer has spread, and standard treatments are not working or available.

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I am 18 years old or older.

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I have had 5 or fewer previous treatments for my condition.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot eat or drink due to a blockage or condition.

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I have previously received treatments targeting the immune system.

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I am not taking any drugs that affect CYP3A4 or taking fluoxetine.

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I have an active heart condition.

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I do not have any unmanaged ongoing illnesses.

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I do not have active hepatitis or infections needing IV antibiotics.

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My cancer is a type of sarcoma or non-epithelial.

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I am allergic to certain medications similar to nivolumab, ipilimumab, or ZEN003694.

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I haven't taken high doses of steroids or immunosuppressants in the last 14 days.

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I have had issues like severe gut infections, blockages, or cancer spread in my abdomen.

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I have active brain metastases or cancer in the lining of my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year post-treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety and tolerability

Secondary study objectives

Circulating tumor deoxyribonucleic acid

Clinical benefit

Incidence of adverse events

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Triplet treatment (nivolumab, ZEN003694, ipilimumab)Experimental Treatment9 Interventions

Patients receive nivolumab IV over 30 minutes on day 1, ipilimumab IV over 90 minutes on day 1, and ZEN003694 PO QD on days 1-21 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 5, patients are no longer treated with ipilimumab, but receive nivolumab IV over 30 minutes on day 1 and ZEN003694 PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI, a CT scan, a PET scan, and/or an x-ray as well as blood sample collection throughout the trial. Patients also undergo a biopsy during screening and on study.

Group II: Doublet treatment (ZEN003694, nivolumab)Experimental Treatment8 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 and ZEN003694 PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI, a CT scan, a PET scan, and/or an x-ray as well as blood sample collection throughout the trial. Patients also undergo a biopsy during screening.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Nivolumab

2015

Completed Phase 3

~4010

Positron Emission Tomography

2011

Completed Phase 2

~2200

Biopsy

2014

Completed Phase 4

~1150

Biospecimen Collection

2004

Completed Phase 3

~2030

Computed Tomography

2017

Completed Phase 2

~2790

Ipilimumab

2015

Completed Phase 3

~3420

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

BET bromodomain inhibitors like ZEN-3694 block proteins necessary for gene transcription involved in cell growth, thereby inhibiting tumor growth. Nivolumab and ipilimumab are monoclonal antibodies that enhance the immune system's ability to attack cancer cells by targeting and blocking the PD-1 and CTLA-4 receptors, respectively. These treatments are significant for cancer patients as they offer targeted and potentially more effective therapeutic options, leading to improved outcomes and personalized treatment plans.

Recurrent glioma clinical trial, CheckMate-143: the game is not over yet.