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
- Conditions
- Hepatocellular CarcinomaSolid TumorHepatocellular Carcinoma Non-resectableHepatocellular Carcinoma RecurrentHepatocellular CancerLiver CancerLiver, Cancer Of, Non-Resectable
- Interventions
- Drug: OTX-2002Drug: Tyrosine kinase inhibitor OneDrug: Checkpoint Inhibitor, ImmuneDrug: Tyrosine kinase inhibitor Two
- Registration Number
- NCT05497453
- Lead Sponsor
- Omega Therapeutics
- 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.
- Detailed 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 190
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OTX-2002 + Tyrosine Kinase Inhibitor One Tyrosine kinase inhibitor One 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 OTX-2002 + Checkpoint Inhibitor Checkpoint Inhibitor, Immune 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 OTX-2002 + Tyrosine Kinase Inhibitor Two Tyrosine kinase inhibitor Two 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 OTX-2002 + Tyrosine Kinase Inhibitor One OTX-2002 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 OTX-2002 OTX-2002 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 + Checkpoint Inhibitor OTX-2002 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 OTX-2002 + Tyrosine Kinase Inhibitor Two OTX-2002 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
- Primary Outcome Measures
Name Time Method Overall response rate (ORR)(for Part 1 and Part 2 expansion) through treatment completion, up to two years 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 2CIncidence of TEAEs including all AEs,Grade 3-5 AEs, drug-related AEs, and SAEs (Part 1 escalation and Part 2 safety run-in) 30 days after the last dose of study drug The incidence of TEAEs, SAEs, and TEAEs leading to study drug discontinuation will be summarized for all patients.
Determine Dose limiting toxicities (DLT)and maximum tolerated dose ( MTD) (Part 1 escalation and Part 2 safety run-in) 28 days/4 weeks from the first dose of OTX-2002 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.
Duration of Response (DOR) (for Part 1 and Part 2 expansion) through treatment completion, up to two years Duration of Complete Response and Partial Response
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (15)
University of Chicago
🇺🇸Chicago, Illinois, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
City of Hope
🇺🇸Duarte, California, United States
University of Florida Health Cancer Center
🇺🇸Gainesville, Florida, United States
Stephenson Cancer Center at Oklahoma University
🇺🇸Oklahoma City, Oklahoma, United States
Fred Hutch / University of Washington
🇺🇸Seattle, Washington, United States
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
National Cancer Center Singapore
🇸🇬Singapore, Singapore
National University Hospital
🇸🇬Singapore, Singapore
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan