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
Overview
- Phase
- Phase 1
- Intervention
- MT-303
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Myeloid Therapeutics
- Enrollment
- 70
- Locations
- 9
- Primary Endpoint
- Change from baseline in ECG parameters
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
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.
Arms & Interventions
MT-303
Participants will receive MT-303 through intravenous infusion.
Intervention: MT-303
MT-303 + Atezolizumab + Bevacizumab
Participants will receive MT-303 in combination with Atezo/Bev through intravenous infusion.
Intervention: MT-303 +Atezolizumab + Bevacizumab
Outcomes
Primary Outcomes
Change from baseline in ECG parameters
Time Frame: Screening, Day 1 and Day 15
Type, incidence and severity of Adverse Events
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: Up to 30 days from the last dose of IMP
Hematology, chemistry, coagulation, virology and urine analysis will be assessed.
Secondary Outcomes
- 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 hypersensitivity reaction(Up to 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)
- 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.)
- To assess adverse events of special interest (AESI) by checking for second primary malignancy(upto 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)