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

Primary Purpose

Urothelial Carcinoma, Triple Negative Breast Cancer, Non-small Cell Lung Cancer

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

SBT6290

pembrolizumab

About this trial

This is an interventional treatment trial for Urothelial Carcinoma focused on measuring SBT6290, breast cancer, urothelial carcinoma, non-small cell lung cancer, squamous cell carcinoma of head and neck, TLR8, Nectin-4, pembrolizumab (KEYTRUDA)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Part 1: SBT6290

Part 2: SBT6290

Part 3: SBT6290 + pembrolizumab

Part 4: SBT6290 + pembrolizumab

Arm Description

SBT6290 every 3 weeks

SBT6290 plus pembrolizumab every 3 weeks

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

Secondary Outcome Measures

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.

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.

Rate of Disease Control for Participants: All Parts

Complete response, partial response, and stable disease as assessed by RECIST Version 1.1 Criteria.

Progression-free Survival: Part 2

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

Maximum concentration (Cmax).

Estimates of Selected PK Parameters for SBT6290: All Parts

Area under the plasma concentration versus time curve (AUC).

Incidence of SBT6290 Antidrug Antibodies (ADA): All Parts

Number of participants positive for ADA.

Full Information

NCT ID

NCT05234606

First Posted

January 13, 2022

Last Updated

April 4, 2022

Sponsor

Silverback Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT05234606

Brief Title

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

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor decision based on strategic re-alignment

Study Start Date

March 2022 (Anticipated)

Primary Completion Date

March 31, 2022 (Actual)

Study Completion Date

March 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Silverback Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: SBT6290

Arm Type

Experimental

Arm Description

SBT6290 every 3 weeks

Arm Title

Part 2: SBT6290

Arm Type

Experimental

Arm Description

SBT6290 every 3 weeks

Arm Title

Part 3: SBT6290 + pembrolizumab

Arm Type

Experimental

Arm Description

SBT6290 plus pembrolizumab every 3 weeks

Arm Title

Part 4: SBT6290 + pembrolizumab

Arm Type

Experimental

Arm Description

SBT6290 plus pembrolizumab every 3 weeks

Intervention Type

Drug

Intervention Name(s)

SBT6290

Intervention Description

Escalating doses by subcutaneous (SC) injection in 21-day cycles

Intervention Type

Drug

Intervention Name(s)

SBT6290

Intervention Description

Dose expansion with the recommended Phase 2 dose (RP2D) by SC injection in 21-day cycles

Intervention Type

Drug

Intervention Name(s)

pembrolizumab

Other Intervention Name(s)

KEYTRUDA

Intervention Description

200 mg via intravenous (IV) injection in 21-day cycles

Primary Outcome Measure Information:

Title

Number of Participants With Dose Limiting Toxicities: Part 1 and Part 3

Description

Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0.

Time Frame

Up to 28 days after the first dose of SBT6290

Title

Number of Participants With Treatment-emergent Adverse Events: All Parts

Description

Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0.

Time Frame

From enrollment to 30 days after the last dose of SBT6290, up to 2 years

Title

Number of Participants With an Objective Response Rate: Part 2 and Part 4

Description

Complete response and partial response as assessed by RECIST Version 1.1 Criteria.

Time Frame

From enrollment to confirmed response, up to 1 year

Title

Duration of Response for Participants With an Objective Response Rate: Part 2 and Part 4

Description

Complete response and partial response as assessed by RECIST Version 1.1 Criteria.

Time Frame

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 Measure Information:

Title

Number of Participants With an Objective Response Rate: Part 1 and Part 3

Description

Complete response and partial response as assessed by RECIST Version 1.1 Criteria.

Time Frame

From enrollment to confirmed response, up to 1 year

Title

Duration of Response for Participants With an Objective Response Rate: Part 1 and Part 3

Description

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.

Time Frame

From enrollment until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 3 years

Title

Rate of Disease Control for Participants: All Parts

Description

Complete response, partial response, and stable disease as assessed by RECIST Version 1.1 Criteria.

Time Frame

Up to at least 6 months after the first dose of SBT6290

Title

Progression-free Survival: Part 2

Description

Complete response, partial response, stable disease, and progressive disease as assessed by RECIST Version 1.1 Criteria.

Time Frame

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

Title

Estimates of Selected PK Parameters for SBT6290: All Parts

Description

Maximum concentration (Cmax).

Time Frame

Immediately before and after SBT6290 doses up to 2 years

Title

Estimates of Selected PK Parameters for SBT6290: All Parts

Description

Area under the plasma concentration versus time curve (AUC).

Time Frame

Immediately before and after SBT6290 doses up to 2 years

Title

Incidence of SBT6290 Antidrug Antibodies (ADA): All Parts

Description

Number of participants positive for ADA.

Time Frame

Immediately before and after SBT6290 doses for up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Natasha Angra, PharmD

Organizational Affiliation

Silverback Therapeutics, Inc.

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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