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

A Phase 1/1B, Open-Label, Dose Escalation and Expansion Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced Solid Tumors Expressing HER2

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

Study Overview

• Status: Active, not recruiting
• Conditions: HER2 Positive Solid Tumors
• Intervention / Treatment: Drug: SBT6050; Drug: pembrolizumab; Drug: Cemiplimab

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 Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University Hospital Clinical Trials Unit
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Breast Cancer Research Centre - WA
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Duke University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute/Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • The START Center for Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SBT6050 Monotherapy; Escalating doses of SBT6050 in Part 1 followed by expansion in Part 2 at the recommended dose determined in Part 1.	Drug: SBT6050; Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2
Experimental: SBT6050 and 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.	Drug: SBT6050; Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2; Drug: pembrolizumab; 400 mg IV
Experimental: SBT6050 and cemiplimab; SBT6050 in combination with cemiplimab in Part 5 at the recommended dose determined in Parts 1 and 3.	Drug: SBT6050; Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2; Drug: Cemiplimab; 350 mg IV

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Silverback Therapeutics
• Investigators: Study Director: Naomi Hunder, MD, Silverback Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Breast Cancer; Non-Small Cell Lung Cancer; HER2; Immunotherapy; Gastric Cancer; Pembrolizumab; Colorectal Cancer; Triple Negative Breast Cancer; Head and neck cancer; Gastrointestinal Cancer; Stomach Cancer; Endometrial cancer; Antibody drug conjugate; Urothelial cancer; Biliary tract cancer; TLR8; Cemiplimab; ERBB2; Gastroesophageal junction; TLR8 agonist; Anti-PD-1 mAb
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab; Cemiplimab
• Other Study ID Numbers: SBT6050-101

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