A Safety and Preliminary Efficacy Study of SBT6290 Alone and in Combination With PD-(L)1 Inhibitors in Select Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a first-in-human, open-label, multicenter, dose-escalation and expansion study designed to investigate SBT6290 administered alone and in combination with pembrolizumab in advanced solid tumors associated with Nectin-4 expression.

Detailed Description
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This is a first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, immunogenicity, and preliminary antitumor activity of SBT6290 administered subcutaneously (SC) as a monotherapy and in combination with pembrolizumab in solid tumors associated with Nectin-4 expression. There are 4 parts to this study: Part 1: A dose escalation of SBT6290 monotherapy Part 2: Tumor-specific expansion cohorts evaluating SBT6290 monotherapy administered at the recommended phase 2 dose (RP2D) identified in Part 1 Part 3: A dose escalation of SBT6290 in combination with pembrolizumab Part 4: An expansion cohort of SBT6290 in combination with pembrolizumab administered at the RP2D identified in Part 3 for the combination

Official Title
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A Phase 1/2, Open-Label, Dose-Escalation and Expansion Study of SBT6290 Alone and in Combination With PD-(L)1 Inhibitors in Subjects With Advanced Solid Tumors Associated With Nectin-4 Expression

Conditions
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Urothelial Carcinoma, Triple Negative Breast Cancer, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Hormone Receptor-positive/HER2-negative Breast Cancer

Intervention / Treatment
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* Drug: SBT6290
* Drug: SBT6290
* Drug: pembrolizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Locally advanced or metastatic solid tumors associated associated with Nectin-4 expression (locally advanced or metastatic urothelial carcinoma, TNBC, NSCLC, SCCHN, and HR+/HER2- negative breast cancer) Measurable disease per the the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria Tumor lesion amenable for biopsy available to submit for retrospective baseline testing of Nectin-4; archived tumor tissue may be acceptable depending upon study Part detailed criteria ECOG Performance Status of 0 or 1 Adequate organ and marrow function Note: Other protocol-defined inclusion/exclusion criteria may apply. Key Exclusion Criteria: History of allergic reactions to certain components of study treatments Untreated brain metastases Currently active (or history of) autoimmune disease Taking the equivalent of >10 mg / day of prednisone Uncontrolled or clinically significant interstitial lung disease (ILD) History of ongoing, uncontrolled, symptomatic eye disorders requiring intervention or associated with marked visual field defects or limiting age-appropriate instrumental activities of daily living HIV infection, active hepatitis B or hepatitis C infection Note: Other 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: Part 1: SBT6290<br>SBT6290 every 3 weeks | Drug: SBT6290<br>* Escalating doses by subcutaneous (SC) injection in 21-day cycles<br>|
| Experimental: Part 2: SBT6290<br>SBT6290 every 3 weeks | Drug: SBT6290<br>* Dose expansion with the recommended Phase 2 dose (RP2D) by SC injection in 21-day cycles<br>|
| Experimental: Part 3: SBT6290 + pembrolizumab<br>SBT6290 plus pembrolizumab every 3 weeks | Drug: SBT6290<br>* Escalating doses by subcutaneous (SC) injection in 21-day cycles<br>Drug: pembrolizumab<br>* 200 mg via intravenous (IV) injection in 21-day cycles<br>* Other names: KEYTRUDA;|
| Experimental: Part 4: SBT6290 + pembrolizumab<br>SBT6290 plus pembrolizumab every 3 weeks | Drug: SBT6290<br>* Dose expansion with the recommended Phase 2 dose (RP2D) by SC injection in 21-day cycles<br>Drug: pembrolizumab<br>* 200 mg via intravenous (IV) injection in 21-day cycles<br>* Other names: KEYTRUDA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities: Part 1 and Part 3 | Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. | Up to 28 days after the first dose of SBT6290 | 
| Number of Participants With Treatment-emergent Adverse Events: All Parts | Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. | From enrollment to 30 days after the last dose of SBT6290, up to 2 years | 
| Number of Participants With an Objective Response Rate: Part 2 and Part 4 | Complete response and partial response as assessed by RECIST Version 1.1 Criteria. | From enrollment to confirmed response, up to 1 year | 
| Duration of Response for Participants With an Objective Response Rate: Part 2 and Part 4 | Complete response and partial response as assessed by RECIST Version 1.1 Criteria. | From enrollment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Objective Response Rate: Part 1 and Part 3 | Complete response and partial response as assessed by RECIST Version 1.1 Criteria. | From enrollment to confirmed response, up to 1 year | 
| Duration of Response for Participants With an Objective Response Rate: Part 1 and Part 3 | The length of time from the participant's first complete response or partial response as assessed by RECIST Version 1.1 Criteria until disease progression or death. | From enrollment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years | 
| Rate of Disease Control for Participants: All Parts | Complete response, partial response, and stable disease as assessed by RECIST Version 1.1 Criteria. | Up to at least 6 months after the first dose of SBT6290 | 
| Progression-free Survival: Part 2 | Complete response, partial response, stable disease, and progressive disease as assessed by RECIST Version 1.1 Criteria. | From first dose of SBT6290 until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years | 
| Estimates of Selected PK Parameters for SBT6290: All Parts | Maximum concentration (Cmax). | Immediately before and after SBT6290 doses up to 2 years | 
| Estimates of Selected PK Parameters for SBT6290: All Parts | Area under the plasma concentration versus time curve (AUC). | Immediately before and after SBT6290 doses up to 2 years | 
| Incidence of SBT6290 Antidrug Antibodies (ADA): All Parts | Number of participants positive for ADA. | Immediately before and after SBT6290 doses for up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SBT6290, breast cancer, urothelial carcinoma, non-small cell lung cancer, squamous cell carcinoma of head and neck, TLR8, Nectin-4, pembrolizumab (KEYTRUDA)