This is a multicenter, open-label, Phase 1, first-in-human, dose-escalation studydesigned to assess the safety, tolerability and define the RP2D of MT-303 alone (Module1) and in combination with Atezo/Bev (Module 2) in participants with advancedhepatocellular carcinoma expressing GPC3.
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.
Drug: MT-303
MT-303
Drug: MT-303 +Atezolizumab + Bevacizumab
MT-303 in combination with Atezo/Bev
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.
St Vincent's Hospital
Sydney, New South Wales, Australia
Integrated Clinical Oncology Network (ICON) Pty Ltd
Woolloongabba, Queensland, Australia
The Alfred Hospital
Melbourne, Victoria, Australia
Linear Clinical Research
Murdoch, Western Australia, Australia
Pusan National Univesity Hospital
Busan, South Korea
Cha University Bundang Medical Center
Gyeonggi-do, South Korea
Seoul National University Hospital
Seoul, South Korea
National Taiwan University Hospital
Taipei, Taiwan
Taipei Tzu Chi Hospital
Taipei, Taiwan
Project Manager
+61 2 8569 1400
Lucy.FrereScott@novotech-cro.com
Clinical Department
+1 617 465 1022
303clinical@myeloidtx.com
Matthew Maurer, MD, Study Director
Myeloid Therapeutics