A Study of MT-303 in Adults With Advanced or Metastatic GPC3-Expressing Cancers, Including HCC

A Phase 1, Open-Label, First-in-Human, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MT-303 in Adults With Advanced or Metastatic GPC3-Expressing Cancers, Including Hepatocellular Carcinoma

This is a multicenter, open-label, Phase 1, first-in-human, dose-escalation study designed to assess the safety, tolerability and define the RP2D of MT-303 alone (Module 1) and in combination with Atezo/Bev (Module 2) in participants with advanced hepatocellular carcinoma expressing GPC3.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: MT-303; Drug: MT-303 +Atezolizumab + Bevacizumab

Detailed Description

Participants will be enrolled into one of two treatment modules:

• Module 1 (Monotherapy): Participants will receive MT-303.
• Module 2 (Combination therapy): Participants will receive MT-303 in combination with atezolizumab + bevacizumab (Atezo/Bev).

In Module 1 (Monotherapy), participants will receive MT-303 across five dose-escalation cohorts and in Module 2 (Combination therapy), participants will receive MT-303 in combination with Atezo/Bev across five dose-escalation cohorts.

Additional cohorts in both modules may be scheduled based on emerging safety and PK data.

Participants will be sequentially enrolled into Cohorts 1 through 5. Both modules will be enrolled concurrently, with Module 2 dosing beginning at one dose level below the known safe dose in Module 1. Safety Review Committee decisions will be informed by all available safety data from Modules 1 and 2.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Department; Phone Number: +1 617 465 1022; Email: 303clinical@myeloidtx.com
• Study Contact Backup: Name: Project Manager; Phone Number: +61 2 8569 1400; Email: Lucy.FrereScott@novotech-cro.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • Recruiting
      • St Vincent's Hospital
      • Contact: Hao-Wen Sim, MD
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Integrated Clinical Oncology Network (ICON) Pty Ltd
      • Contact: Vladimir Andelkovic, MD
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
      • Contact: Stuart Roberts, MD
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Recruiting
      • Linear Clinical Research
      • Contact: Tim Humphries, MD
• South Korea
  • Busan, South Korea
    • Recruiting
    • Pusan National Univesity Hospital
    • Contact: Jeong Heo, MD
  • Gyeonggi-do, South Korea
    • Recruiting
    • CHA University Bundang Medical Center
    • Contact: Hongjae Jeoon, MD
  • Seoul, South Korea
    • Recruiting
    • Seoul National University Hospital
    • Contact: Yoon Jun Kim, MD
• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chih-hung Hsu
  • Taipei, Taiwan
    • Recruiting
    • Taipei Tzu Chi Hospital
    • Contact: Her-shyong Shiah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Aged 18 years or older
• Histological diagnosis of advanced/recurrent or metastatic and/or unresectable HCC. [Note: participants with other tumor types expressing GPC3 may be eligible for Module 1 pending a discussion with the Medical Monitor. Only participants with HCC are eligible for Module 2.
• Measurable lesion per RECIST 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
• Child-Pugh score: Class A
• Adequate organ function

General Exclusion Criteria

• Known active CNS metastasis and/or carcinomatous meningitis.
• Any acute illness including active infection
• History of liver transplantation or on waiting list
• Participants with untreated or incompletely treated varices with bleeding or high risk for bleeding
• Uncontrolled pleural effusion, pericardial effusion, or ascites
• History of symptomatic congestive heart failure
• History of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immune-suppressive treatments.

Additional Module 2 Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Significant cardiovascular disease
• History of severe hypersensitivity to atezolizumab and/or bevacizumab.
• History of idiopathic pulmonary fibrosis
• Prior history of hypertensive crisis or hypertensive encephalopathy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MT-303; Participants will receive MT-303 through intravenous infusion.	Drug: MT-303; MT-303
Experimental: MT-303 + Atezolizumab + Bevacizumab; Participants will receive MT-303 in combination with Atezo/Bev through intravenous infusion.	Drug: MT-303 +Atezolizumab + Bevacizumab; MT-303 in combination with Atezo/Bev

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (RP2D)	The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data	28 days from the last dose of IMP
Change from baseline in ECG parameters		Screening, Day 1 and Day 15
Type, incidence and severity of Adverse Events	Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0	Up to 2 years from the last dose of Investigational Medicinal Product (IMP)
Change from baseline in vital signs	Temperature, weight, height, pulse rate and blood pressure will be assessed	Up to 30 days from the last dose of IMP
Change in laboratory parameters	Hematology, chemistry, coagulation, virology and urine analysis will be assessed.	Up to 30 days from the last dose of IMP
Optimal Biological dose (OBD)	The OBD will be determined using dose limiting toxicities (DLTs) and all other available study data	21 days from the last dose of IMP

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess adverse events of special interest (AESI) by measuring infusion reaction		upto 2 years from the last dose of IMP
To assess adverse events of special interest (AESI) by measuring cytokine release syndrome (CRS)		Up to 2 years from the last dose of IMP
To assess adverse events of special interest (AESI) by measuring immune effector cell-associated neurotoxicity syndrome (ICANS)		Up to 2 years from the last dose of IMP
To assess adverse events of special interest (AESI) by measuring hypersensitivity reaction		Up to 2 years from the last dose of IMP
To assess adverse events of special interest (AESI) by checking for second primary malignancy		upto 2 years from the last dose of IMP
Pharmacokinetics (PK)	PK parameter: Plasma concentrations	Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)	PK parameter: Area under Curve	Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)	PK parameter: Time of maximum observed plasma concentration (tmax)	Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)	PK parameter: Plasma Clearance (CL)	Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)	PK parameter: Volume of Distribution (Vd)	Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)	PK parameter: Mean residence time (MRT)	Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)	PK parameter: terminal rate constant (λz)	Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.

Collaborators and Investigators

• Sponsor: Myeloid Therapeutics
• Collaborators: CREATE Medicines
• Investigators: Study Director: Matthew Maurer, MD, Myeloid Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: June 24, 2024
• First Submitted That Met QC Criteria: June 24, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Liver Cancer; Chimeric antigen receptor; Hepatocellular Carcinoma (HCC); Glypican-3; CAR-M
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Simpson-Golabi-Behmel syndrome; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab
• Other Study ID Numbers: MTX-GPC3-303

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No