Clinical trial NCT04460456: A Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced HER2 Expressing Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: HER2 Positive Solid Tumors
Keywords: HER2
ERBB2
Immunotherapy
Gastric Cancer
Gastroesophageal junction
Breast Cancer
Triple Negative Breast Cancer
Stomach Cancer
Colorectal Cancer
Gastrointestinal Cancer
Non-Small Cell Lung Cancer
Monoclonal antibody
TLR8
TLR8 agonist
Antibody drug conjugate
Biliary tract cancer
Head and neck cancer
Urothelial cancer
Endometrial cancer
Pembrolizumab
Anti-PD-1 mAb
Cemiplimab
Lead sponsor: Silverback Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-07-07
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of subjects experiencing dose limiting toxicities
timeFrame: 28 days
measure: The incidence and severity of adverse events (AEs) and serious adverse events
timeFrame: 2 years
measure: Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR)
timeFrame: 2 years
measure: Duration of response, defined as the time from date of first response (CR or PR)
timeFrame: 2 years
Secondary outcomes:
measure: Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR)
timeFrame: 2 years
measure: Duration of response, defined as the time from date of first response (CR or PR)
timeFrame: 2 years
measure: Disease control rate, defined as CR, PR, or stable disease for at least 6 months
timeFrame: 2 years
measure: Estimates of selected pharmacokinetics (PK ) parameters for SBT6050
timeFrame: 2 years
measure: Estimates of selected pharmacokinetics (PK ) parameters for SBT6050
timeFrame: 2 years
measure: Incidence of antidrug antibodies (ADA) to SBT6050
timeFrame: 2 years
measure: Progression free survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute/Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: The START Center for Cancer Care
state: Texas
city: Sydney
country: Australia
facility: Macquarie University Hospital Clinical Trials Unit
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Breast Cancer Research Centre - WA
state: Western Australia
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Silverback Therapeutics
name: Naomi Hunder, MD
role: STUDY_DIRECTOR
References: