OTX-2002 for Liver Cancer

(MYCHELANGELO I Trial)

No longer recruiting at 19 trial locations

Overseen By Head of Clinical Development Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Omega Therapeutics

Must be taking: Antivirals

Disqualifiers: CNS metastases, Ascites, Variceal bleeding, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called OTX-2002 for liver cancer and other tumors linked to the MYC oncogene, which influences cell growth. The goal is to determine if OTX-2002 is safe and effective, both alone and in combination with other treatments. Participants should have advanced liver cancer unresponsive to standard care and may have tried other treatments without success. The study includes phases where OTX-2002 is administered alone and with other cancer drugs to identify the most effective approach. Individuals with liver cancer that hasn't responded to other treatments might be suitable for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, if you have chronic hepatitis B, you must continue antiviral therapy for at least 12 weeks before starting the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that OTX-2002 demonstrated positive safety results in earlier studies. Most side effects were mild to moderate, indicating they were not serious and patients generally tolerated them well. The studies involved individuals with liver cancer and other tumors related to the MYC gene. Although detailed safety information for each combination with other drugs, such as checkpoint inhibitors or tyrosine kinase inhibitors, is limited, the initial results appear promising. As this is an early-stage trial, the primary goal is to ensure the treatment's safety and manageability of any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about OTX-2002 for liver cancer because it offers a fresh approach compared to current treatments like surgery, radiation, or chemotherapy. OTX-2002 is unique as it works by targeting specific proteins in cancer cells, potentially disrupting their growth more effectively. Unlike standard therapies, which often have broad effects on both healthy and cancerous cells, OTX-2002 aims for precision, potentially leading to fewer side effects. Additionally, when combined with immune checkpoint inhibitors or tyrosine kinase inhibitors, OTX-2002 could enhance the body's own immune response or interfere with cancer cell signaling pathways, offering a multi-faceted attack on the cancer.

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

Research has shown that OTX-2002 targets the MYC gene, often linked to cancer growth. This treatment lowers MYC levels, potentially slowing cancer cell growth. In lab studies, OTX-2002 reduced liver cancer cell survival and helped shrink tumors. Participants in this trial may receive OTX-2002 alone or with other treatments, such as checkpoint inhibitors or tyrosine kinase inhibitors. These combinations may enhance its cancer-fighting effects. Overall, early results suggest it could be a helpful approach for treating liver cancer related to the MYC gene. ^{2 4 5 6 7}

Who Is on the Research Team?

Yan Moore, MD

Principal Investigator

Omega Therapeutics

Are You a Good Fit for This Trial?

Adults over 18 with advanced liver cancer (hepatocellular carcinoma) or solid tumors linked to the MYC gene, who've tried standard treatments without success. They must have a good performance status and controlled hepatitis B if present. Those with severe liver complications, brain metastases, recent bleeding from esophageal varices, or specific types of mixed liver cancers cannot join.

Inclusion Criteria

My liver cancer is at an intermediate or advanced stage and cannot be treated with local therapies.

My condition worsened or didn't improve after at least 1 treatment, and no standard treatment options are left.

My cancer has spread, can't be surgically removed, or has come back and doesn’t respond to standard treatments.

Exclusion Criteria

My cancer has spread to the main blood vessel of my liver.

I have brain metastases or carcinomatous meningitis that hasn't been treated.

I have not had hepatic encephalopathy in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Dose Escalation

Participants receive OTX-2002 monotherapy to determine dose limiting toxicity and maximum tolerated dose

4 weeks

Every 2 weeks (in-person)

Part 1: Expansion

Participants receive OTX-2002 at the recommended dose for expansion to evaluate overall response rate and duration of response

Up to 2 years

Every 2 weeks (in-person)

Part 2: Safety Run-in

Participants receive OTX-2002 in combination with standard of care therapies to determine safety and tolerability

4 weeks

Every 2 weeks (in-person)

Part 2: Expansion

Participants receive OTX-2002 in combination with standard of care therapies to evaluate overall response rate and duration of response

Up to 2 years

Every 2 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• OTX-2002

Trial Overview OTX-2002 is being tested alone and alongside standard treatments for its safety and effectiveness against certain cancers. The trial has two parts: first testing OTX-2002 by itself (monotherapy), then in combination with other cancer drugs (combination therapy).

How Is the Trial Designed?

Group I: OTX-2002 + Tyrosine Kinase Inhibitor Two Experimental Treatment 2 Interventions

OTX-2002 + Tyrosine Kinase Inhibitor Two : (Cycle length = 4 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks. Tyrosine Kinase Inhibitor Two will be standard per the respective fixed local approved dose

Group II: OTX-2002 + Tyrosine Kinase Inhibitor One Experimental Treatment 2 Interventions

OTX-2002 + Tyrosine Kinase Inhibitor One: (Cycle length = 4 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks. Tyrosine Kinase Inhibitor One will be standard per the respective fixed local approved dose

Group III: OTX-2002 + Checkpoint Inhibitor Experimental Treatment 2 Interventions

OTX-2002 + Immune Checkpoint Blockade: (Cycle length = 6 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks. Checkpoint Inhibitor will be standard per the respective fixed local approved dose

Group IV: OTX-2002 Experimental Treatment 1 Intervention

Monotherapy: OTX-2002 (Cycle length = 4 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks

OTX-2002 is already approved in United States for the following indications:

Approved in United States as OTX-2002 for:

• Hepatocellular carcinoma (Orphan Drug Designation)

Who Is Running the Clinical Trial?

Omega Therapeutics

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

In a study of 101 hepatocellular carcinoma (HCC) patients treated with anti-PD-1 antibodies, those who experienced immune-related adverse events (irAEs) had a significantly higher tumor response rate (28.6% vs 6.3%) and longer median progression-free survival (14.8 months vs 4.1 months) compared to those without irAEs.

Among the irAEs, rash was the most common and was associated with the best outcomes, indicating that the presence of irAEs, particularly rash, could serve as an independent prognostic factor for improved survival in HCC patients receiving anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events predict responses to PD-1 blockade immunotherapy in hepatocellular carcinoma. Lu, L., Xing, K., Wei, W., et al.[2021]

The implementation of the ROTOX tool in the electronic medical record significantly improved the documentation of radiation toxicities, with the documentation quality score rising from 41% to 99% within six months and maintaining at 96% three years later.

The ROTOX system allowed for the identification of 107 episodes of high-grade toxicity in 4,443 on-treatment visits, with 95% of these cases having documented interventions, demonstrating its efficacy in enhancing patient management and safety in radiation oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic Medical Record-Based Radiation Oncology Toxicity Recording Instrument Aids Benchmarking and Quality Improvement in the Clinic. Albuquerque, K., Rodgers, K., Spangler, A., et al.[2019]

A review of 166 phase III randomized clinical trials published between 2011 and 2013 revealed frequent misreporting of adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0), indicating a significant issue in adherence to established guidelines.

Inappropriate grading of toxicities was common, with serious conditions like febrile neutropenia often graded too low, and less severe conditions like alopecia graded too high, which could mislead clinicians and affect treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and misuse of common terminology criteria for adverse events in cancer clinical trials. Zhang, S., Liang, F., Tannock, I.[2018]

Liver transplantation (LTx) can lead to prolonged cancer-free survival in patients with cirrhosis and hepatocellular carcinoma (HCC), with an 82% survival rate at 22.5 months post-transplant for those meeting selection criteria.

Among the 28 patients with cirrhosis and HCC studied, 87% survived for 1 year and 76% for 3 years post-LTx, showing comparable survival rates to those undergoing LTx for other malignancies and benign conditions, indicating the efficacy of LTx in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An active liver transplant programme for hepatocellular carcinoma in cirrhotic patients: is it justified? Chui, AK., Rao, AR., McCaughan, GW., et al.[2022]

In a study of 260 liver transplantations performed on 238 patients, including 63 with hepatocellular carcinoma (HCC), the overall survival rates at 1, 3, and 5 years were 94%, 76%, and 76%, respectively, indicating that liver transplantation can be a viable option for selected patients with unresectable HCC.

The study found that careful tumor staging and selection of patients based on factors like TNM stage and pre-transplant AFP levels are crucial for improving survival outcomes after orthotopic liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver transplantation for hepatocellular carcinoma: prognostic factors associated long-term survival. Colella, G., Rondinara, GF., De Carlis, L., et al.[2019]

Objective response (OR) measured by modified RECIST (mRECIST) is an independent predictor of overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC), based on a systematic review of 34 randomized clinical trials involving 14,056 patients.

While OR-mRECIST shows a better correlation with OS than OR-RECIST, the surrogacy is considered modest, suggesting it can be used as an endpoint in early phase trials but not as a primary endpoint in larger phase III studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Objective Response Predicts Survival in Advanced Hepatocellular Carcinoma Treated with Systemic Therapies. Kudo, M., Montal, R., Finn, RS., et al.[2022]

The North Central Cancer Treatment Group developed a real-time toxicity reporting system to enhance the monitoring of severe side effects in NCI-sponsored clinical trials, aiming to improve patient safety.

This system has been effective in monitoring phase II and III trials, such as the N9741 study on advanced colorectal cancer, allowing for timely modifications to ongoing clinical trials based on reported adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early detection of toxicity and adjustment of ongoing clinical trials: the history and performance of the North Central Cancer Treatment Group's real-time toxicity monitoring program. Goldberg, RM., Sargent, DJ., Morton, RF., et al.[2016]

In a study of 396 colorectal cancer patients who underwent liver metastasectomy, reduced CDX2 expression was found in 9.1% of cases and was associated with significantly poorer disease-free survival (DFS) and overall survival (OS), indicating it may serve as a prognostic biomarker for high-risk relapse.

Patients with low CDX2 expression had a median DFS of only 245 days and a median OS of 1024 days, compared to 420 days and 3145 days for those with high CDX2 expression, suggesting that CDX2 levels could help predict patient outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis. Shigematsu, Y., Inamura, K., Yamamoto, N., et al.[2022]

In a study of 19 patients who underwent liver transplantation for hepatocellular carcinoma (HCC), both those with known HCC and those with incidental HCC showed similar rates of tumor-free survival and disease characteristics.

Patients with incidental HCC had a significantly better survival rate (100%) compared to those with known HCC, suggesting that early detection and treatment may improve outcomes after liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orthotopic liver transplantation in hepatocellular carcinoma: comparison of results in incidental and known hepatocellular carcinoma. Toufeeq Khan, TF., Reddy, KS., Johnston, TD., et al.[2009]

OTX1 is significantly overexpressed in human hepatocellular carcinoma (HCC) tissues compared to non-cancerous tissues, and its expression correlates with more advanced disease features like nodal metastasis and TNM staging.

Knocking down OTX1 in HCC cell lines reduces cell proliferation and migration, induces cell cycle arrest, and inhibits tumor growth in an animal model, suggesting that OTX1 may be a promising target for molecular therapy in HCC by affecting the ERK/MAPK signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OTX1 Contributes to Hepatocellular Carcinoma Progression by Regulation of ERK/MAPK Pathway. Li, H., Miao, Q., Xu, CW., et al.[2018]

In a study of 1136 pediatric oncology patients treated for solid tumors, 14% experienced liver injury, with drug-induced liver injury (DILI) being the most common cause at 31%.

Most DILI cases were mild and did not require changes to chemotherapy, while non-DILI liver injuries were more severe and associated with higher mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and Sequelae of Liver Injury Among Children Treated for Solid Tumors: Analysis of a Large Single-Center Prospective Cohort. Cardenas, V., Mankuzhy, N., Mody, R., et al.[2022]

In a study of 181 patients with hepatocellular carcinoma (HCC) treated between 1980 and 1989, those who underwent orthotopic liver transplantation (TX) had significantly better survival rates compared to those who had subtotal hepatic resection (HX) when HCC was associated with liver cirrhosis.

Both treatment methods had high tumor recurrence rates, particularly in advanced stages, indicating a need for additional nonsurgical anti-cancer therapies to improve long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic resection versus transplantation for hepatocellular carcinoma. Iwatsuki, S., Starzl, TE., Sheahan, DG., et al.[2022]

Liver transplantation (LTx) has seen significant improvements, achieving a one-year patient survival rate of around 90% due to better patient selection, surgical techniques, and postoperative care.

Despite these advancements, challenges remain, such as managing the side effects of long-term immunosuppression and addressing the shortage of donor organs, which limits the broader application of LTx.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present status and future prospects in liver transplantation. Pirenne, J., Koshiba, T.[2009]

Liver transplantation (LTX) for hepatocellular carcinoma (HCC) has shown significant improvements in patient survival rates over three decades, with 5-year survival rates increasing from 25.3% in 1983-1990 to 67.8% in 1997-2005.

The characteristics of tumors in patients undergoing LTX have also improved, with a notable decrease in tumor size and number of nodules, indicating better patient selection and management strategies, although the rate of microvascular invasion remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved results of transplantation for hepatocellular carcinoma: a report from the International Registry of Hepatic Tumors in Liver Transplantation. Onaca, N., Davis, GL., Jennings, LW., et al.[2010]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05497453

NCT05497453 | A Phase 1/2 Study to Evaluate OTX-2002 ... This is a Phase 1/2 open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as ...

2. withpower.com withpower.com/trial/phase-2-non-resectable-hepatocellular-carcinoma-7-2022-84dd2

OTX-2002 for Liver Cancer (MYCHELANGELO I Trial) The available research does not provide specific data on the effectiveness of OTX-2002 for Liver Cancer. Instead, it focuses on liver transplantation and other ...

3. clin.larvol.com clin.larvol.com/trial-detail/NCT05497453

A Phase 1/2 Study to Evaluate OTX-2002 in Patients with ... Advanced the Phase 1/2 MYCHELANGELO I clinical trial evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC): Omega expects to report additional ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11405918/

Targeted transcriptional downregulation of MYC using ... Collectively, these results indicated that OTX-2002-mediated downregulation of MYC enhances the antitumor activity of lenvatinib and sorafenib ...

5. synapse.patsnap.com synapse.patsnap.com/article/omega-therapeutics-publishes-otx-2002-preclinical-data-in-nature-communications

Omega Therapeutics Publishes OTX-2002 Preclinical Data ... OTX-2002, specifically, has shown precise engagement with the c-MYC oncogene, leading to its downregulation at both mRNA and protein levels, ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.TPS627

A phase 1/2 open-label study to evaluate the safety, ... OTX-2002 is being evaluated in an open-label, non-randomized, phase 1/2 study (MYCHELANGELO I) in patients with HCC and other advanced solid tumor types.

7. cancernetwork.com cancernetwork.com/view/otx-2002-shows-encouraging-safety-in-small-hepatocellular-carcinoma-cohort

OTX-2002 Shows Encouraging Safety in Small ... Most adverse effects appear to be grade 1 or 2 among patients with hepatocellular carcinoma and other solid tumors associated with the MYC ...