Overview
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.
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.
Eligibility
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.
