A Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced HER2 Expressing Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1/1B, Open-Label, Dose Escalation and Expansion Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced Solid Tumors Expressing HER2

Conditions
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HER2 Positive Solid Tumors

Intervention / Treatment
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* Drug: SBT6050
* Drug: pembrolizumab
* Drug: Cemiplimab


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBT6050 Monotherapy<br>Escalating doses of SBT6050 in Part 1 followed by expansion in Part 2 at the recommended dose determined in Part 1. | Drug: SBT6050<br>* Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2<br>|
| Experimental: SBT6050 and pembrolizumab<br>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. | Drug: SBT6050<br>* Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2<br>Drug: pembrolizumab<br>* 400 mg IV<br>|
| Experimental: SBT6050 and cemiplimab<br>SBT6050 in combination with cemiplimab in Part 5 at the recommended dose determined in Parts 1 and 3. | Drug: SBT6050<br>* Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2<br>Drug: Cemiplimab<br>* 350 mg IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects experiencing dose limiting toxicities | Part 1 and 3 only | 28 days | 
| The incidence and severity of adverse events (AEs) and serious adverse events | Parts 1, 2, 3, 4, and 5 | 2 years | 
| Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR) | Parts 2, 4, and 5 | 2 years | 
| Duration of response, defined as the time from date of first response (CR or PR) | Parts 2, 4, and 5 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR) | Parts1 and 3 only | 2 years | 
| Duration of response, defined as the time from date of first response (CR or PR) | Parts 1 and 3 only | 2 years | 
| Disease control rate, defined as CR, PR, or stable disease for at least 6 months | Parts 1, 2, 3, 4, and 5 | 2 years | 
| Estimates of selected pharmacokinetics (PK ) parameters for SBT6050 | Cmax: Parts 1, 2, 3, 4, and 5 | 2 years | 
| Estimates of selected pharmacokinetics (PK ) parameters for SBT6050 | AUC: Parts 1, 2, 3, 4, and 5 | 2 years | 
| Incidence of antidrug antibodies (ADA) to SBT6050 | Parts 1 and 2 | 2 years | 
| Progression free survival | Parts 2, 4, and 5 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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