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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05234606
• Other study ID #: SBT6290-101
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: March 2022
• Est. completion date: March 31, 2022

Study information

• Verified date: April 2022
• Source: Silverback Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 31, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Carcinoma, Transitional Cell
• Non-small Cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Carcinoma

Intervention

Drug:
• SBT6290
Escalating doses by subcutaneous (SC) injection in 21-day cycles
• SBT6290
Dose expansion with the recommended Phase 2 dose (RP2D) by SC injection in 21-day cycles
• pembrolizumab
200 mg via intravenous (IV) injection in 21-day cycles

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Silverback Therapeutics

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Estimates of Selected PK Parameters for SBT6290: All Parts	Maximum concentration (Cmax).	Immediately before and after SBT6290 doses up to 2 years
Secondary	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
Secondary	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