Clinical trial NCT05234606: A Safety and Preliminary Efficacy Study of SBT6290 Alone and in Combination With PD-(L)1 Inhibitors in Select Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: 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
Keywords: SBT6290
breast cancer
urothelial carcinoma
non-small cell lung cancer
squamous cell carcinoma of head and neck
TLR8
Nectin-4
pembrolizumab (KEYTRUDA)
Lead sponsor: Silverback Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-02-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities: Part 1 and Part 3
timeFrame: Up to 28 days after the first dose of SBT6290
measure: Number of Participants With Treatment-emergent Adverse Events: All Parts
timeFrame: From enrollment to 30 days after the last dose of SBT6290, up to 2 years
measure: Number of Participants With an Objective Response Rate: Part 2 and Part 4
timeFrame: From enrollment to confirmed response, up to 1 year
measure: Duration of Response for Participants With an Objective Response Rate: Part 2 and Part 4
timeFrame: 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 outcomes:
measure: Number of Participants With an Objective Response Rate: Part 1 and Part 3
timeFrame: From enrollment to confirmed response, up to 1 year
measure: Duration of Response for Participants With an Objective Response Rate: Part 1 and Part 3
timeFrame: From enrollment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years
measure: Rate of Disease Control for Participants: All Parts
timeFrame: Up to at least 6 months after the first dose of SBT6290
measure: Progression-free Survival: Part 2
timeFrame: 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
measure: Estimates of Selected PK Parameters for SBT6290: All Parts
timeFrame: Immediately before and after SBT6290 doses up to 2 years
measure: Estimates of Selected PK Parameters for SBT6290: All Parts
timeFrame: Immediately before and after SBT6290 doses up to 2 years
measure: Incidence of SBT6290 Antidrug Antibodies (ADA): All Parts
timeFrame: Immediately before and after SBT6290 doses for up to 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Silverback Therapeutics, Inc.
name: Natasha Angra, PharmD
role: STUDY_DIRECTOR
References: