HER2 Positive Solid Tumors
Conditions
Keywords
HER2, ERBB2, Immunotherapy, Gastric Cancer, Gastroesophageal junction, Breast Cancer, Triple Negative Breast Cancer, Stomach Cancer, Colorectal Cancer, Gastrointestinal Cancer, Non-Small Cell Lung Cancer, Monoclonal antibody, TLR8, TLR8 agonist, Antibody drug conjugate, Biliary tract cancer, Head and neck cancer, Urothelial cancer, Endometrial cancer, Pembrolizumab, Anti-PD-1 mAb, Cemiplimab
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.
Interventions
DRUGSBT6050
Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2
DRUGpembrolizumab
400 mg IV
DRUGCemiplimab
350 mg IV
Sponsors
Silverback Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of subjects experiencing dose limiting toxicities | 28 days | Part 1 and 3 only |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of antidrug antibodies (ADA) to SBT6050 | 2 years | Parts 1 and 2 |
| Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR) | 2 years | Parts1 and 3 only |
| Progression free survival | 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 1 and 3 only |
| Disease control rate, defined as CR, PR, or stable disease for at least 6 months | 2 years | Parts 1, 2, 3, 4, and 5 |
| Estimates of selected pharmacokinetics (PK ) parameters for SBT6050 | 2 years | Cmax: Parts 1, 2, 3, 4, and 5 |
Countries
Australia, South Korea, United States
Outcome results
None listed