Hepatocellular Carcinoma
Conditions
Keywords
Liver Cancer, Hepatocellular Carcinoma (HCC), Glypican-3, Chimeric antigen receptor, CAR-M
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 alone (Module 1) and in combination with Atezo/Bev (Module 2) in participants with advanced hepatocellular carcinoma expressing GPC3.
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.
Interventions
DRUGMT-303
MT-303
DRUGMT-303 +Atezolizumab + Bevacizumab
MT-303 in combination with Atezo/Bev
Sponsors
CREATE Medicines
Myeloid Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in ECG parameters | Screening, Day 1 and Day 15 | — |
| Type, incidence and severity of Adverse Events | Up to 2 years from the last dose of Investigational Medicinal Product (IMP) | Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0 |
| Recommended Phase 2 Dose (RP2D) | 28 days from the last dose of IMP | The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data |
| Optimal Biological dose (OBD) | 21 days from the last dose of IMP | The OBD will be determined using dose limiting toxicities (DLTs) and all other available study data |
| Change from baseline in vital signs | Up to 30 days from the last dose of IMP | Temperature, weight, height, pulse rate and blood pressure will be assessed |
| Change in laboratory parameters | Up to 30 days from the last dose of IMP | Hematology, chemistry, coagulation, virology and urine analysis will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) | 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. | PK parameter: Plasma concentrations |
| 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 | — |
Countries
Australia, South Korea, Taiwan
Contacts
Primary ContactProject Manager
Backup ContactClinical Department
Outcome results
None listed