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

NCT05497453 | Terminated Phase 1 FDA Drug

• 1 other identifier: OTX-2002-101
• Study Type: interventional
• Target: 24
• Locations: 5 countries
• Sites: 15

Brief 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.

Conditions

Hepatocellular Carcinoma; Solid Tumor; Hepatocellular Carcinoma Non-resectable; Hepatocellular Carcinoma Recurrent; Hepatocellular Cancer; Liver Cancer; Liver, Cancer Of, Non-Resectable

Keywords

MYC; C-MYC; MYC Amplification; MYC Overexpression; MRNA; Epigenetics

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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

Study Arms (4)

OTX-2002

EXPERIMENTAL

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

Drug: OTX-2002

OTX-2002 + Tyrosine Kinase Inhibitor One

EXPERIMENTAL

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

Drug: OTX-2002; Drug: Tyrosine kinase inhibitor One

OTX-2002 + Tyrosine Kinase Inhibitor Two

EXPERIMENTAL

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

Drug: OTX-2002; Drug: Tyrosine kinase inhibitor Two

OTX-2002 + Checkpoint Inhibitor

EXPERIMENTAL

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

Drug: OTX-2002; Drug: Checkpoint Inhibitor, Immune

Interventions

OTX-2002 DRUG

OTX-2002 is a lipid nanoparticle (LNP) that contains a biscistronic mRNA that codes for 2 independent epigenomic controllers.

OTX-2002; OTX-2002 + Checkpoint Inhibitor; OTX-2002 + Tyrosine Kinase Inhibitor One; OTX-2002 + Tyrosine Kinase Inhibitor Two

Tyrosine kinase inhibitor One DRUG

Tyrosine Kinase Inhibitor

OTX-2002 + Tyrosine Kinase Inhibitor One

Tyrosine kinase inhibitor Two DRUG

tyrosine kinase inhibitor

OTX-2002 + Tyrosine Kinase Inhibitor Two

Checkpoint Inhibitor, Immune DRUG

monoclonal antibody that binds to PD-1 or PD-L1

OTX-2002 + Checkpoint Inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Omega Therapeutics: lead

Study Sites (15)

City of Hope

Duarte, California, 91010, United States

Location

University of Florida Health Cancer Center

Gainesville, Florida, 32610, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Stephenson Cancer Center at Oklahoma University

Oklahoma City, Oklahoma, 73104, United States

Location

Fred Hutch / University of Washington

Seattle, Washington, 98109, United States

Location

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

National Cancer Center Singapore

Singapore, Singapore

Location

National University Hospital

Singapore, Singapore

Location

Asan Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Yan Moore, MD

  Omega Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 OTX-2002 monotherapy dose escalation and expansion in participants with hepatocellular carcinoma (HCC) and other solid tumors During the monotherapy dose escalation phase, participants will be enrolled in sequential cohorts of increasing doses of OTX-2002. Part 2 of the study is a safety run-in and expansion study of OTX-2002 participants with HCC will be administered OTX-2002 in combination with tyrosine kinase inhibitor One (Part 2A), Tyrosine Kinase Inhibitor Two (Part 2B), or Checkpoint Inhibitor (Part 2C).

Study Record Dates

• First Submitted: August 8, 2022
• First Posted: August 11, 2022
• Study Start: August 19, 2022
• Primary Completion: November 21, 2024
• Study Completion: November 21, 2024
• Last Updated: February 3, 2025

Record last verified: 2024-09

Locations

HK (2); TW (2); KR (3); US (6); SG (2)