Clinical trial NCT06478693: A Study of MT-303 in Adults With Advanced or Metastatic GPC3-Expressing Cancers, Including HCC
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: Liver Cancer
Hepatocellular Carcinoma (HCC)
Glypican-3
Chimeric antigen receptor
CAR-M
Lead sponsor: Myeloid Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-06-27
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 in participants with advanced hepatocellular carcinoma expressing GPC3.

Detailed description: MT-303 will be administered intravenously with treatment provided until lack of tolerability or progression. Participants will be enrolled in sequential dose escalation cohorts with determination of dose limiting toxicities with the goal of establishing the (maximum tolerated dose) MTD and (Recommended Phase 2 dose) RP2D.

Eligibility criteria: Inclusion Criteria

* Aged 18 years or older
* Histological diagnosis of advanced/recurrent or metastatic and/or unresectable HCC. \[Note: participants with other tumor types expressing GPC3 may be eligible pending a discussion with the Medical Monitor\]
* 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

Exclusion Criteria

* Known active central nervous system (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.

Primary outcomes:
measure: Type, incidence and severity of Adverse Events
timeFrame: Up to 2 years from the last dose of Investigational Medicinal Product (IMP)
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: 28 days from the last dose of IMP
measure: Change from baseline in vital signs
timeFrame: Up to 30 days from the last dose of IMP
measure: Change in laboratory parameters
timeFrame: Up to 30 days from the last dose of IMP
measure: Change from baseline in ECG parameters
timeFrame: Screening, Day 1 and Day 15
Secondary outcomes:
measure: To assess the pharmacokinetics (PK) of MT-303
timeFrame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP
measure: To assess the pharmacokinetics (PK) of MT-303
timeFrame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP
measure: To assess the pharmacokinetics (PK) of MT-303
timeFrame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP
measure: To assess the pharmacokinetics (PK) of MT-303
timeFrame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP
measure: To assess the pharmacokinetics (PK) of MT-303
timeFrame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP
measure: To assess the pharmacokinetics (PK) of MT-303
timeFrame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP
measure: To assess the pharmacokinetics (PK) of MT-303
timeFrame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP
measure: To assess adverse events of special interest (AESI) by measuring infusion reaction
timeFrame: upto 2 years from the last dose of IMP
measure: To assess adverse events of special interest (AESI) by measuring cytokine release syndrome (CRS)
timeFrame: Up to 2 years from the last dose of IMP
measure: To assess adverse events of special interest (AESI) by measuring immune effector cell-associated neurotoxicity syndrome (ICANS)
timeFrame: Up to 2 years from the last dose of IMP
measure: To assess adverse events of special interest (AESI) by measuring hypersensitivity reaction
timeFrame: Up to 2 years from the last dose of IMP
measure: To assess adverse events of special interest (AESI) by checking for second primary malignancy
timeFrame: upto 2 years from the last dose of IMP
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Integrated Clinical Oncology Network (ICON) Pty Ltd
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Busan
country: Korea, Republic of
facility: Pusan National Univesity Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Cha University Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Myeloid Therapeutics
name: Matthew Maurer, MD
role: STUDY_DIRECTOR
References: