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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 (MYCHELANGELO I)

Primary Purpose

Hepatocellular Carcinoma, Solid Tumor, Hepatocellular Carcinoma Non-resectable

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
OTX-2002
Tyrosine kinase inhibitor One
Tyrosine kinase inhibitor Two
Checkpoint Inhibitor, Immune
Sponsored by
Omega Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring MYC, C-MYC, MYC Amplification, MYC Overexpression, MRNA, Epigenetics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • City of HopeRecruiting
  • University of Florida Health Cancer CenterRecruiting
  • Ochsner Clinic FoundationRecruiting
  • Stephenson Cancer Center at Oklahoma UniversityRecruiting
  • Next OncologyRecruiting
  • Fred Hutch / University of WashingtonRecruiting
  • Prince of Wales HospitalRecruiting
  • Queen Mary HospitalRecruiting
  • Asan Medical CenterRecruiting
  • Seoul National University HospitalRecruiting
  • Severance Hospital, Yonsei University Health SystemRecruiting
  • National Cancer Center SingaporeRecruiting
  • National University HospitalRecruiting
  • National Cheng Kung University HospitalRecruiting
  • National Taiwan University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

OTX-2002

OTX-2002 + Tyrosine Kinase Inhibitor One

OTX-2002 + Tyrosine Kinase Inhibitor Two

OTX-2002 + Checkpoint Inhibitor

Arm Description

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 + 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 + 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 + 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

Outcomes

Primary Outcome Measures

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.
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.
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
Duration of Response (DOR) (for Part 1 and Part 2 expansion)
Duration of Complete Response and Partial Response

Secondary Outcome Measures

Full Information

First Posted
August 8, 2022
Last Updated
June 27, 2023
Sponsor
Omega Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05497453
Brief Title
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
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 19, 2022 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Omega Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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).
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
190 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
OTX-2002
Arm Type
Experimental
Arm Description
Monotherapy: OTX-2002 (Cycle length = 4 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks
Arm Title
OTX-2002 + Tyrosine Kinase Inhibitor One
Arm Type
Experimental
Arm Description
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
Arm Title
OTX-2002 + Tyrosine Kinase Inhibitor Two
Arm Type
Experimental
Arm Description
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
Arm Title
OTX-2002 + Checkpoint Inhibitor
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
OTX-2002
Intervention Description
OTX-2002 is a lipid nanoparticle (LNP) that contains a biscistronic mRNA that codes for 2 independent epigenomic controllers.
Intervention Type
Drug
Intervention Name(s)
Tyrosine kinase inhibitor One
Intervention Description
Tyrosine Kinase Inhibitor
Intervention Type
Drug
Intervention Name(s)
Tyrosine kinase inhibitor Two
Intervention Description
tyrosine kinase inhibitor
Intervention Type
Drug
Intervention Name(s)
Checkpoint Inhibitor, Immune
Intervention Description
monoclonal antibody that binds to PD-1 or PD-L1
Primary Outcome Measure Information:
Title
Determine Dose limiting toxicities (DLT)and maximum tolerated dose ( MTD) (Part 1 escalation and Part 2 safety run-in)
Description
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.
Time Frame
28 days/4 weeks from the first dose of OTX-2002
Title
Incidence of TEAEs including all AEs,Grade 3-5 AEs, drug-related AEs, and SAEs (Part 1 escalation and Part 2 safety run-in)
Description
The incidence of TEAEs, SAEs, and TEAEs leading to study drug discontinuation will be summarized for all patients.
Time Frame
30 days after the last dose of study drug
Title
Overall response rate (ORR)(for Part 1 and Part 2 expansion)
Description
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
Time Frame
through treatment completion, up to two years
Title
Duration of Response (DOR) (for Part 1 and Part 2 expansion)
Description
Duration of Complete Response and Partial Response
Time Frame
through treatment completion, up to two years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Head of Clinical Development Operations
Phone
617-949-4378
Email
clinicaltrials@omegatx.com
First Name & Middle Initial & Last Name or Official Title & Degree
Chief Medical Officer
Phone
617-949-4378
Email
clinicaltrials@omegatx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hao-Fei Tiffany Wang, MD
Organizational Affiliation
Omega Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daneng Li
Phone
626-471-9200
Email
danli@coh.org
Facility Name
University of Florida Health Cancer Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Taryn King
Phone
352-733-0299
Email
King.taryn@ufl.edu
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharon Jerdonek
Phone
504-842-3929
Email
sharon.jerdonek@ochsner.org
Facility Name
Stephenson Cancer Center at Oklahoma University
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susanna V Ulahannan
Phone
405-217-3020
Ext
48955
Email
susanna-ulahannan@ouhsc.edu
Facility Name
Next Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cynthia DeLeon
Phone
210-580-9521
Email
cdeleon@nextoncology.com
Facility Name
Fred Hutch / University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
GI Nurse Navigator
Phone
206-606-4800
Email
ginursenavslu@seattlecca.org
Facility Name
Prince of Wales Hospital
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephen Lam Cham
Phone
85-2-3505-1042
Email
chanlam_stephen@cuhk.edu.hk
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Chung Cheung Yau
Phone
852-2255-1661
Email
tyaucc@hku.hk
Facility Name
Asan Medical Center
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min-hee Ryu
Phone
82-2-3010-5935
Email
miniryu@amc.seoul.kr
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tae-Yong Kim
Phone
82-2-2072-4748
Email
ktyongmd@gmail.com
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Choong-Kun Lee
Phone
82-2-2228-8122
Email
cklee512@yuhs.ac
Facility Name
National Cancer Center Singapore
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Tai Wai-Meng
Phone
65-6436-8000
Email
clinical.trials@nccs.com.sg
Facility Name
National University Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yong Wei Peng
Phone
65-6773-7888
Email
ncis@nuhs.edu.sg
Facility Name
National Cheng Kung University Hospital
City
Tainan
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chia-Jui Yen
Phone
886-912-377366
Email
yencj@mail.ncku.edu.tw
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chia-Chi Lin
Phone
886-919-171-263
Email
cclin1@ntu.edu.tw

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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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

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