EP31670 for Advanced Cancer

Recruiting at 5 trial locations

Overseen By Judy Chiao, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Epigenetix, Inc.

Must not be taking: Antibiotics, Antifungals

Disqualifiers: CNS metastasis, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks per cycle

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called EP31670 (also known as NEO2734) for certain advanced cancers. Researchers aim to assess its safety and impact on tumors. The trial tests three methods of administering the treatment, either alone or with other medications. Individuals with specific advanced cancers, such as recurrent prostate cancer or certain blood cancers, may qualify if previous treatments have failed. Participants should be able to manage daily activities independently.

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 requires a four-week period without prior anti-cancer therapy, including chemotherapy, immunotherapy, or investigational anti-cancer therapy, before starting the study. This suggests you may need to stop certain medications, but the protocol does not specify all medications that must be stopped.

Is there any evidence suggesting that EP31670 is likely to be safe for humans?

In earlier studies, EP31670, also known as NEO2734, showed promising results in lab and animal tests by targeting specific proteins that aid cancer growth. These studies suggest it might effectively fight tumors.

For the combination treatment with ruxolitinib or momelotinib, some safety information is available. Long-term use of momelotinib was studied, and serious infections were rare. However, some patients reported diarrhea, with a small percentage experiencing severe cases. Ruxolitinib is commonly used, and researchers are studying how EP31670 interacts with it.

Although this is the first study involving humans, meaning there's limited information on its safety in people, the research so far appears hopeful. Always consult a doctor to understand the potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about EP31670 for advanced cancer because it offers a fresh approach compared to standard treatments like chemotherapy and targeted therapies. Unlike most cancer treatments that target cancer cell growth or division directly, EP31670 is designed to be taken orally and works through a unique dose-escalation strategy, potentially optimizing its effectiveness while minimizing side effects. Additionally, the combination use of EP31670 with ruxolitinib or momelotinib in one of the trial arms could enhance its efficacy by targeting multiple pathways involved in cancer progression. This innovative approach might provide more tailored treatment options for patients with advanced cancer.

What evidence suggests that EP31670 might be an effective treatment for advanced cancer?

Research has shown that EP31670, also known as NEO2734, demonstrates promising effects against tumors in lab and animal studies. This drug blocks BET and CBP/p300 proteins, which often aid cancer cell growth. Studies on prostate cancer and acute myeloid leukemia suggest it could effectively fight cancer. In this trial, some participants will receive EP31670 alone, while others will receive it with drugs like ruxolitinib or momelotinib. These combination treatments have already shown some success in treating myelofibrosis, a type of cancer affecting the bone marrow. ^{1 6 7 8 9}

Who Is on the Research Team?

Judy Chiao, MD

Principal Investigator

Epigenetix, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, like prostate cancer or neuroendocrine tumors. Participants must be relatively healthy and active (ECOG 0-1), have a life expectancy of at least 3 months, and proper organ function. They should not have had recent cancer treatments or major surgery and must agree to use contraception. It's not for pregnant women, those with severe heart issues, uncontrolled illnesses, or specific viral infections.

Inclusion Criteria

For fertile men and women, agreement to use effective contraceptive methods duration of study participation and 4 weeks after the last dose of study drug

I am fully active or can carry out light work.

It has been at least 4 weeks since my major surgery.

Exclusion Criteria

I am receiving antiviral treatment for hepatitis B or C.

Corrected QT interval ≥470 msec

Pregnant or lactating women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EP31670 in a dose-escalation study to determine the maximum tolerated dose

3 weeks per cycle

Multiple visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• EP31670

Trial Overview EP31670 is being tested in this Phase 1 trial. It's a first-in-human study focusing on patients with targeted advanced solid tumors who may benefit from dual BET and CBP/p300 inhibition—a new approach aimed at stopping tumor growth by targeting specific proteins involved in cancer cell survival.

How Is the Trial Designed?

Group I: Part 3 Experimental Treatment 1 Intervention

Patients will be assigned escalated dose according to BOIN design. The starting dose is 10 mg orally once a day for 14 consecutive days in combination with ruxolitinib or momelotinib followed by 14 days of rest according to the traditional 3 + 3 design by the modified Fibonacci sequence

Group II: Part 2 Experimental Treatment 1 Intervention

Patients will be assigned escalated dose according to BOIN design. The starting dose is 20 mg orally once a day for 14 consecutive days followed by 14 days of rest.

Group III: Part 1 Experimental Treatment 1 Intervention

Patients will be assigned escalated dose according to BOIN design. The starting dose is 5 mg orally once a day for 7 consecutive days followed by 14 days of rest.

Who Is Running the Clinical Trial?

Epigenetix, Inc.

Lead Sponsor

Trials

1

Recruited

80+

Published Research Related to This Trial

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

Over half of the oral antineoplastic agents (OAAs) approved by the European Medicines Agency (EMA) are associated with cardiotoxic adverse events, particularly blood pressure alterations and QT interval prolongation, highlighting the need for careful monitoring during treatment.

Specific dose adjustment recommendations exist for some OAAs regarding cardiotoxicity, such as those for QT prolongation and left ventricular ejection fraction (LVEF) decrease, emphasizing the importance of pre-treatment cardiovascular risk assessment and potential referral to cardio-oncology specialists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication guide for dose adjustment and management of cardiotoxicity and lipid metabolic adverse events of oral antineoplastic therapy. Ramos-Ruperez, E., Escudero-Vilaplana, V., Ruiz-Briones, P., et al.[2023]

A structured guide was developed to enhance the safety and efficacy of oral antineoplastic agents (OAA) for onco-hematologic outpatients, addressing critical areas such as dosing, drug interactions, and adverse event management.

The guide serves as a checklist for pharmacists during patient education, aiming to standardize care and improve adherence, ultimately leading to better patient outcomes in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guiding pharmacist clinical interviews: a safety tool to support the education of patients treated with oral antineoplastic agents. Ribed, A., Escudero-Vilaplana, V., Romero-Jimenez, RM., et al.[2016]

Oral antineoplastic therapy can lead to various cardiovascular adverse events, with 20 studies highlighting significant cardiac issues such as reduced left ventricular ejection fraction, myocardial infarction, and heart failure.

Peripheral vascular events, including hypertension and thromboembolism, were also noted, indicating that patients undergoing oral cancer treatments should be monitored for both cardiac and vascular complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular adverse events associated with oral antineoplastic therapy. Silva, JMD., Lima, BDS., Araújo, TL., et al.[2019]

A systematic review of 128 randomized clinical trials involving 47,432 patients showed that anticancer drugs provided a statistically significant benefit in progression-free survival (PFS) and overall survival (OS) compared to best supportive care, with hazard ratios of 0.58 and 0.82, respectively.

Despite these benefits, the absolute gains in survival were modest, with PFS extending by only 2.1 months and OS by 0.5 months, and there was a weak correlation between severe toxicity and treatment efficacy, indicating that higher toxicity did not necessarily lead to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and benefits of anticancer drugs in advanced cancer patients: A systematic review and meta-analysis. Moreau Bachelard, C., Coquan, E., du Rusquec, P., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05488548

Dual BET and CBP/p300 Inhibitor in Patients With Targeted ... EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor which has demonstrated antitumor activity in in vitro and in vivo models ...

2. withpower.com withpower.com/trial/phase-1-castration-resistant-prostate-cancer-8-2022-63d7e

EP31670 for Advanced Cancer This trial is for adults with certain advanced solid tumors, like prostate cancer or neuroendocrine tumors. Participants must be relatively healthy and active ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6553796/

SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib ... A ≥ 50% reduction in the total symptom score was observed in 28.4% and 42.2% of patients who received momelotinib and ruxolitinib, respectively, indicating that ...

4. targetedonc.com targetedonc.com/view/long-term-survival-demonstrated-with-momelotnib-in-myelofibrosis

Long-Term Survival Demonstrated With Momelotinib in ... In SIMPLIFY-2, the median OS was 34.3 months for patients originally assigned to momelotinib and 37.5 months (HR = .96; P = .86) for those ...

5. cancertherapyadvisor.com cancertherapyadvisor.com/news/momelotinib-vs-ruxolitinib-for-myelofibrosis-phase-3-trial-yields-mixed-results/

Momelotinib vs Ruxolitinib for Myelofibrosis: Phase 3 Trial ... Momelotinib was non-inferior to ruxolitinib for the primary endpoint of 35% or greater spleen-volume reduction (26.5% vs 29%, respectively; P = ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10368854/

Momelotinib long-term safety and survival in myelofibrosis Serious opportunistic infections were uncommon and did not lead to death. Nonmelanoma skin cancer was observed with long-term momelotinib treatment (4.8%), ...

7. mdanderson.org mdanderson.org/documents/Departments-and-Divisions/Leukemia/Leukemia%20Insights%20Newsletter_March%202024%20Clinical%20trials%20for%20patients%20with%20MF%20Established%20approaches%20and%20new%20paradigms.pdf

Leukemia Insights March 2024 It is being studied in the “add on” setting in patients on a stable dose of ruxolitinib who have palpable splenomegaly, symptoms or cytopenias. CK0804 is ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37042865/

Momelotinib long-term safety and survival in myelofibrosis The most common nonhematologic treatment-emergent adverse event (AE) occurring in ≥20% of patients was diarrhea (any grade, 27% and grade ≥3, 3 ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0163725824000561

Characteristics of anticancer activity of CBP/p300 inhibitors We revise the possible and clinically relevant off-targets of CBP/p300 inhibitors that can be blocked simultaneously with CBP/p300 thereby improving the ...