A Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced HER2 Expressing Solid Tumors
- Conditions
- HER2 Positive Solid Tumors
- Interventions
- Registration Number
- NCT04460456
- Lead Sponsor
- Silverback Therapeutics
- Brief Summary
A first-in-human (FIH) study using SBT6050 and SBT6050 in combination with PD-1 inhibitors in HER2 expressing or amplified advanced malignancies
- Detailed Description
This study has 5 parts. Part 1 will evaluate the safety, tolerability, and activity of escalating doses of SBT6050 to estimate the maximum tolerated dose (MTD) and determine the dose recommended for Part 2. Part 2 of the study will further evaluate SBT6050 in select HER2 expressing or amplified advanced malignancies.
Part 3 will evaluate the safety, tolerability, and activity of escalating doses of SBT6050 in combination with pembrolizumab to estimate the MTD and determine the dose recommended for Part 4. Part 4 of the study will further evaluate SBT6050 in combination with pembrolizumab in select HER2 expressing or amplified advanced malignancies.
Part 5 of the study will evaluate the safety, tolerability, and activity of SBT6050 in combination with cemiplimab in select HER2 expressing or amplified advanced malignancies.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 58
- Locally advanced or metastatic HER2-expressing (IHC 2+ or 3+) or amplified solid tumor
- Subjects must have received prior therapies known to confer clinical benefit (unless ineligible or refused to receive)
- Measurable disease per RECIST 1.1
- Tumor lesion amenable for biopsy or able to provide tissue from biopsy within last 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate hematologic, hepatic, and cardiac function
- History of allergic reactions to certain components of SBT6050 or similar drugs
- Untreated brain metastases
- Active autoimmune disease or a documented history of autoimmune disease or syndrome
- Human immunodeficiency virus infection, active hepatitis B infection or hepatitis C infection
- Additional protocol defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SBT6050 and pembrolizumab SBT6050 Escalating doses of SBT6050 in combination with pembrolizumab in Part 3 followed by expansion in Part 4 at the recommended dose determined in Part 3. SBT6050 Monotherapy SBT6050 Escalating doses of SBT6050 in Part 1 followed by expansion in Part 2 at the recommended dose determined in Part 1. SBT6050 and cemiplimab SBT6050 SBT6050 in combination with cemiplimab in Part 5 at the recommended dose determined in Parts 1 and 3. SBT6050 and pembrolizumab pembrolizumab Escalating doses of SBT6050 in combination with pembrolizumab in Part 3 followed by expansion in Part 4 at the recommended dose determined in Part 3. SBT6050 and cemiplimab Cemiplimab SBT6050 in combination with cemiplimab in Part 5 at the recommended dose determined in Parts 1 and 3.
- Primary Outcome Measures
Name Time Method The incidence and severity of adverse events (AEs) and serious adverse events 2 years Parts 1, 2, 3, 4, and 5
Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR) 2 years Parts 2, 4, and 5
Duration of response, defined as the time from date of first response (CR or PR) 2 years Parts 2, 4, and 5
The proportion of subjects experiencing dose limiting toxicities 28 days Part 1 and 3 only
- Secondary Outcome Measures
Name Time Method Progression free survival 2 years Parts 2, 4, and 5
Estimates of selected pharmacokinetics (PK ) parameters for SBT6050 2 years AUC: Parts 1, 2, 3, 4, and 5
Disease control rate, defined as CR, PR, or stable disease for at least 6 months 2 years Parts 1, 2, 3, 4, and 5
Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR) 2 years Parts1 and 3 only
Duration of response, defined as the time from date of first response (CR or PR) 2 years Parts 1 and 3 only
Incidence of antidrug antibodies (ADA) to SBT6050 2 years Parts 1 and 2
Trial Locations
- Locations (12)
University of Pittsburgh Medical Center Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Macquarie University Hospital Clinical Trials Unit
🇦🇺Sydney, New South Wales, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The START Center for Cancer Care
🇺🇸San Antonio, Texas, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Breast Cancer Research Centre - WA
🇦🇺Nedlands, Western Australia, Australia
Duke University
🇺🇸Durham, North Carolina, United States
Sarah Cannon Research Institute/Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of