A Safety and Preliminary Efficacy Study of SBT6290 Alone and in Combination With PD-(L)1 Inhibitors in Select Advanced Solid Tumors
- Conditions
- Triple Negative Breast CancerHormone Receptor-positive/HER2-negative Breast CancerNon-small Cell Lung CancerSquamous Cell Carcinoma of Head and NeckUrothelial Carcinoma
- Interventions
- Registration Number
- NCT05234606
- Lead Sponsor
- Silverback Therapeutics
- 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
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: SBT6290 SBT6290 SBT6290 every 3 weeks Part 2: SBT6290 SBT6290 SBT6290 every 3 weeks Part 4: SBT6290 + pembrolizumab SBT6290 SBT6290 plus pembrolizumab every 3 weeks Part 3: SBT6290 + pembrolizumab SBT6290 SBT6290 plus pembrolizumab every 3 weeks Part 3: SBT6290 + pembrolizumab pembrolizumab SBT6290 plus pembrolizumab every 3 weeks Part 4: SBT6290 + pembrolizumab pembrolizumab SBT6290 plus pembrolizumab every 3 weeks
- Primary Outcome Measures
Name Time Method 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 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.
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.
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 Outcome Measures
Name Time Method 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.
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.
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.
Estimates of Selected PK Parameters for SBT6290: All Parts Immediately before and after SBT6290 doses up to 2 years Area under the plasma concentration versus time curve (AUC).