Hormone Receptor-positive/HER2-negative Breast Cancer, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Cancer, Urothelial Carcinoma
Conditions
Keywords
SBT6290, breast cancer, urothelial carcinoma, non-small cell lung cancer, squamous cell carcinoma of head and neck, TLR8, Nectin-4, pembrolizumab (KEYTRUDA)
Brief summary
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
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
Interventions
DRUGSBT6290
Escalating doses by subcutaneous (SC) injection in 21-day cycles
DRUGpembrolizumab
200 mg via intravenous (IV) injection in 21-day cycles
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities: Part 1 and Part 3 | Up to 28 days after the first dose of SBT6290 | Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. |
| Number of Participants With Treatment-emergent Adverse Events: All Parts | From enrollment to 30 days after the last dose of SBT6290, up to 2 years | Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. |
| Number of Participants With an Objective Response Rate: Part 2 and Part 4 | From enrollment to confirmed response, up to 1 year | Complete response and partial response as assessed by RECIST Version 1.1 Criteria. |
| Duration of Response for Participants With an Objective Response Rate: Part 2 and Part 4 | From enrollment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years | Complete response and partial response as assessed by RECIST Version 1.1 Criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimates of Selected PK Parameters for SBT6290: All Parts | Immediately before and after SBT6290 doses up to 2 years | Maximum concentration (Cmax). |
| Number of Participants With an Objective Response Rate: Part 1 and Part 3 | From enrollment to confirmed response, up to 1 year | Complete response and partial response as assessed by RECIST Version 1.1 Criteria. |
| Incidence of SBT6290 Antidrug Antibodies (ADA): All Parts | Immediately before and after SBT6290 doses for up to 2 years | Number of participants positive for ADA. |
| Duration of Response for Participants With an Objective Response Rate: Part 1 and Part 3 | From enrollment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years | 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. |
| Rate of Disease Control for Participants: All Parts | Up to at least 6 months after the first dose of SBT6290 | Complete response, partial response, and stable disease as assessed by RECIST Version 1.1 Criteria. |
| Progression-free Survival: Part 2 | 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 | Complete response, partial response, stable disease, and progressive disease as assessed by RECIST Version 1.1 Criteria. |
Outcome results
None listed