A Phase 1/2 Study to Evaluate OTX-2002 in Patients With Hepatocellular Carcinoma and Other Solid Tumor Types Known for Association With the MYC Oncogene

Hepatocellular Carcinoma Clinical Trial

— MYCHELANGELO I  

Official title:

Phase 1/2 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of OTX-2002 as a Single Agent and in Combination With Standard of Care in Patients With Hepatocellular Carcinoma and Other Solid Tumor Types Known for Association With the MYC Oncogene

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05497453
• Other study ID #: OTX-2002-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 19, 2022
• Est. completion date: December 2028

Study information

• Verified date: December 2023
• Source: Omega Therapeutics
• Contact: Head of Clinical Development Operations
• Phone: 617-949-4378
• Email: clinicaltrials[@]omegatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2 open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as a single agent and in combination with standard of care in patients with hepatocellular carcinoma (HCC) and other solid tumor types known for association with the MYC oncogene. The study consists of Part 1 (OTX-2002 monotherapy) and Part 2 (OTX-2002 combined with standard of care in hepatocellular carcinoma). Part 1 consists of escalation and expansion, and Part 2 consists of safety run-in and expansion. The objective of Part 1 escalation and Part 2 safety run-in will be safety and tolerability, while anti-tumor activity will be evaluated as the primary endpoint in Part 1 and Part 2 expansion.

Description:

This is a Phase 1/2 open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as a single agent and in combination with standard of care in patients with hepatocellular carcinoma (HCC) and other solid tumor types known for association with the MYC oncogene. The study consists of Part 1 (OTX-2002 monotherapy) and Part 2 (OTX-2002 combined with standard of care in hepatocellular carcinoma). In Part 1, during dose escalation, participants with HCC and other solid tumors that progressed on, relapsed after, are refractory to, or are intolerant of standard of care for which no treatment options are available will be administered an intravenous infusion of OTX-2002 as a single agent. The escalation will be conducted using a 3+3 design, with the primary endpoint of dose limiting toxicity (DLT), maximum tolerated dose (MTD), and incidence of treatment emergent adverse events (TEAEs). In Part 1 expansion, 15-25 participants with BCLC stage B or C, Child-Pugh Class A HCC who have received at least 1 prior line of systemic anticancer treatment, and without available subsequent standard of care, will receive OTX-2002 at the recommended dose for expansion (RDE) for monotherapy. The primary endpoint of Part 1 expansion will be overall response rate (ORR) and duration of response (DoR). In Part 2, during safety run-in, participants with BCLC stage B or C, Child-Pugh Class A HCC who have received at least 1 prior line of systemic anticancer treatment, and without available subsequent standard of care, will receive OTX-2002 at the selected dose in combination with standard of care therapies at the local approved dose. The primary endpoint of Part 2 safety run-in will be DLT, MTD, and incidence of TEAE. Once the combination therapies have been determined to be tolerable in the safety run-in, 15-25 HCC participants will be enrolled in Part 2 expansion for each of the combination therapies. The primary endpoint of Part 2 expansion will be ORR and DoR.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: December 2028
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key inclusion

• Participants with metastatic, advanced (non-resectable), or recurrent solid tumor who progressed on, relapsed after, are refractory to, or intolerant of standard of care (only applicable to Part 1 escalation)
• Participants with BCLC Stage B (intermediate stage) or C (advanced stage), Child-Pugh A hepatocellular carcinoma who is not amenable to locoregional therapy, refractory to locoregional therapy or not amenable to curative treatment approach
• Adult participants age = 18 years at the time of signing informed consent
• Participant must have progressed on, have relapsed after, be refractory to, or be intolerant of at least 1 prior systemic therapy, and without available subsequent standard of care
• Participants with chronic hepatitis B must have received antiviral therapy for hepatitis B virus (HBV) for at least 12 weeks and HBV viral load must be < 500 IU/mL prior to first dose of study drug.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Key exclusion
• Mixed histology cholangiocarcinoma and HCC, or fibrolamellar variant HCC
• Hepatocellular carcinoma with = 50% liver occupation
• Clear invasion into the bile duct
• Portal vein invasion with Vp4
• Active/untreated CNS metastases or carcinomatous meningitis
• History of ascites requiring paracentesis within the past 3 months
• Esophageal or gastric variceal bleeding in the past 3 months
• History of hepatic encephalopathy in the past 3 months.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Cancer
• Hepatocellular Carcinoma
• Hepatocellular Carcinoma Non-resectable
• Hepatocellular Carcinoma Recurrent
• Liver Cancer
• Liver Neoplasms
• Liver, Cancer of, Non-Resectable
• Solid Tumor

Intervention

Drug:
• OTX-2002
OTX-2002 is a lipid nanoparticle (LNP) that contains a biscistronic mRNA that codes for 2 independent epigenomic controllers.
• Tyrosine kinase inhibitor One
Tyrosine Kinase Inhibitor
• Tyrosine kinase inhibitor Two
tyrosine kinase inhibitor
• Checkpoint Inhibitor, Immune
monoclonal antibody that binds to PD-1 or PD-L1

Locations

Country	Name	City	State
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Singapore	National Cancer Center Singapore	Singapore
Singapore	National University Hospital	Singapore
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United States	University of Chicago	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	University of Florida Health Cancer Center	Gainesville	Florida
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Stephenson Cancer Center at Oklahoma University	Oklahoma City	Oklahoma
United States	Next Oncology	San Antonio	Texas
United States	Fred Hutch / University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Omega Therapeutics

Countries where clinical trial is conducted

United States,  Hong Kong,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine Dose limiting toxicities (DLT)and maximum tolerated dose ( MTD) (Part 1 escalation and Part 2 safety run-in)	The frequency of DLTs will be tabulated by dose for participants in the dose escalation phase, and information about all DLTs will be listed by dose.	28 days/4 weeks from the first dose of OTX-2002
Primary	Incidence of TEAEs including all AEs,Grade 3-5 AEs, drug-related AEs, and SAEs (Part 1 escalation and Part 2 safety run-in)	The incidence of TEAEs, SAEs, and TEAEs leading to study drug discontinuation will be summarized for all patients.	30 days after the last dose of study drug
Primary	Overall response rate (ORR)(for Part 1 and Part 2 expansion)	ORR (proportion of participants who achieve CR or PR), DCR (proportion of participants who achieve CR, PR, or SD)per mRECIST (for HCC) and RECIST 1.1(for solid tumors), during Parts 1, 2A, 2B,and 2C; •ORR (proportion of participants who achieve CR or PR), DCR (proportion of participants who achieve CR, PR, or SD)per irRECIST during Part 2C	through treatment completion, up to two years
Primary	Duration of Response (DOR) (for Part 1 and Part 2 expansion)	Duration of Complete Response and Partial Response	through treatment completion, up to two years