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

Sponsor

Silverback Therapeutics (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT05234606

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Days)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: SBT6290 Drug: SBT6290 Drug: pembrolizumab	Phase 1/Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 1, 2022

Actual Primary Completion Date :

Mar 31, 2022

Actual Study Completion Date :

Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: SBT6290 SBT6290 every 3 weeks	Drug: SBT6290 Escalating doses by subcutaneous (SC) injection in 21-day cycles
Experimental: Part 2: SBT6290 SBT6290 every 3 weeks	Drug: SBT6290 Dose expansion with the recommended Phase 2 dose (RP2D) by SC injection in 21-day cycles
Experimental: Part 3: SBT6290 + pembrolizumab SBT6290 plus pembrolizumab every 3 weeks	Drug: SBT6290 Escalating doses by subcutaneous (SC) injection in 21-day cycles Drug: pembrolizumab 200 mg via intravenous (IV) injection in 21-day cycles Other Names: KEYTRUDA
Experimental: Part 4: SBT6290 + pembrolizumab SBT6290 plus pembrolizumab every 3 weeks	Drug: SBT6290 Dose expansion with the recommended Phase 2 dose (RP2D) by SC injection in 21-day cycles Drug: pembrolizumab 200 mg via intravenous (IV) injection in 21-day cycles Other Names: KEYTRUDA

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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.
Estimates of Selected PK Parameters for SBT6290: All Parts [Immediately before and after SBT6290 doses up to 2 years]
Maximum concentration (Cmax).
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).
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.