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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Cancer; Non-small Cell Lung Cancer; Urothelial Carcinoma; Hormone Receptor-positive/HER2-negative Breast Cancer
• Intervention / Treatment: Drug: SBT6290; Drug: SBT6290; Drug: pembrolizumab

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 Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: SBT6290; SBT6290 every 3 weeks	Drug: SBT6290; Escalating doses by subcutaneous (SC) injection in 21-day cycles; Drug: SBT6290; Dose expansion with the recommended Phase 2 dose (RP2D) by SC injection in 21-day cycles
Experimental: Part 2: SBT6290; SBT6290 every 3 weeks	Drug: SBT6290; Escalating doses by subcutaneous (SC) injection in 21-day cycles; 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: 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
Experimental: Part 4: SBT6290 + pembrolizumab; SBT6290 plus pembrolizumab every 3 weeks	Drug: SBT6290; Escalating doses by subcutaneous (SC) injection in 21-day cycles; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Silverback Therapeutics
• Investigators: Study Director: Natasha Angra, PharmD, Silverback Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: breast cancer; non-small cell lung cancer; urothelial carcinoma; SBT6290; squamous cell carcinoma of head and neck; TLR8; Nectin-4; pembrolizumab (KEYTRUDA)
• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Head and Neck Neoplasms; Lung Neoplasms; Neoplasms, Squamous Cell; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Carcinoma, Transitional Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: SBT6290-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No