A Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced HER2 Expressing Solid Tumors

Phase 1

• Conditions: HER2 Positive Solid Tumors
• Interventions: Drug: SBT6050; Drug: pembrolizumab; Drug: Cemiplimab

• Registration Number: NCT04460456
• Lead Sponsor: Silverback Therapeutics

Brief Summary

A first-in-human (FIH) study using SBT6050 and SBT6050 in combination with PD-1 inhibitors in HER2 expressing or amplified advanced malignancies

Detailed Description

This study has 5 parts. Part 1 will evaluate the safety, tolerability, and activity of escalating doses of SBT6050 to estimate the maximum tolerated dose (MTD) and determine the dose recommended for Part 2. Part 2 of the study will further evaluate SBT6050 in select HER2 expressing or amplified advanced malignancies.

Part 3 will evaluate the safety, tolerability, and activity of escalating doses of SBT6050 in combination with pembrolizumab to estimate the MTD and determine the dose recommended for Part 4. Part 4 of the study will further evaluate SBT6050 in combination with pembrolizumab in select HER2 expressing or amplified advanced malignancies.

Part 5 of the study will evaluate the safety, tolerability, and activity of SBT6050 in combination with cemiplimab in select HER2 expressing or amplified advanced malignancies.

Study Timeline

• Study First Submitted: 2020-06-29
• Study First Submitted QC: 2020-07-06
• Study First Posted: 2020-07-07
• Study Start: 2020-07-27
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-27
• Last Update Posted: 2022-06-30
• Primary Completion: 2022-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

• Locally advanced or metastatic HER2-expressing (IHC 2+ or 3+) or amplified solid tumor
• Subjects must have received prior therapies known to confer clinical benefit (unless ineligible or refused to receive)
• Measurable disease per RECIST 1.1
• Tumor lesion amenable for biopsy or able to provide tissue from biopsy within last 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematologic, hepatic, and cardiac function

Exclusion Criteria

• History of allergic reactions to certain components of SBT6050 or similar drugs
• Untreated brain metastases
• Active autoimmune disease or a documented history of autoimmune disease or syndrome
• Human immunodeficiency virus infection, active hepatitis B infection or hepatitis C infection
• Additional protocol defined inclusion/exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SBT6050 and pembrolizumab	SBT6050	Escalating doses of SBT6050 in combination with pembrolizumab in Part 3 followed by expansion in Part 4 at the recommended dose determined in Part 3.
SBT6050 Monotherapy	SBT6050	Escalating doses of SBT6050 in Part 1 followed by expansion in Part 2 at the recommended dose determined in Part 1.
SBT6050 and cemiplimab	SBT6050	SBT6050 in combination with cemiplimab in Part 5 at the recommended dose determined in Parts 1 and 3.
SBT6050 and pembrolizumab	pembrolizumab	Escalating doses of SBT6050 in combination with pembrolizumab in Part 3 followed by expansion in Part 4 at the recommended dose determined in Part 3.
SBT6050 and cemiplimab	Cemiplimab	SBT6050 in combination with cemiplimab in Part 5 at the recommended dose determined in Parts 1 and 3.

Primary Outcome Measures

Name	Time	Method
The incidence and severity of adverse events (AEs) and serious adverse events	2 years	Parts 1, 2, 3, 4, and 5
Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR)	2 years	Parts 2, 4, and 5
Duration of response, defined as the time from date of first response (CR or PR)	2 years	Parts 2, 4, and 5
The proportion of subjects experiencing dose limiting toxicities	28 days	Part 1 and 3 only

Secondary Outcome Measures

Name	Time	Method
Estimates of selected pharmacokinetics (PK ) parameters for SBT6050	2 years	AUC: Parts 1, 2, 3, 4, and 5
Disease control rate, defined as CR, PR, or stable disease for at least 6 months	2 years	Parts 1, 2, 3, 4, and 5
Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR)	2 years	Parts1 and 3 only
Duration of response, defined as the time from date of first response (CR or PR)	2 years	Parts 1 and 3 only
Incidence of antidrug antibodies (ADA) to SBT6050	2 years	Parts 1 and 2
Progression free survival	2 years	Parts 2, 4, and 5

Trial Locations

Locations (12)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

University of Pittsburgh Medical Center Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Sarah Cannon Research Institute/Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

The START Center for Cancer Care; 🇺🇸 San Antonio, Texas, United States

Macquarie University Hospital Clinical Trials Unit; 🇦🇺 Sydney, New South Wales, Australia

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

Breast Cancer Research Centre - WA; 🇦🇺 Nedlands, Western Australia, Australia

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

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