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

Sponsor

Silverback Therapeutics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04460456

Collaborator

(none)

Enrollment

Locations

Arms

28.2

Anticipated Duration (Months)

4.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
HER2 Positive Solid Tumors	Drug: SBT6050 Drug: pembrolizumab Drug: Cemiplimab	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

58 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 27, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

The proportion of subjects experiencing dose limiting toxicities [28 days]
Part 1 and 3 only
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

Secondary Outcome Measures

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
Disease control rate, defined as CR, PR, or stable disease for at least 6 months [2 years]
Parts 1, 2, 3, 4, and 5
Estimates of selected pharmacokinetics (PK ) parameters for SBT6050 [2 years]
Cmax: Parts 1, 2, 3, 4, and 5
Estimates of selected pharmacokinetics (PK ) parameters for SBT6050 [2 years]
AUC: Parts 1, 2, 3, 4, and 5
Incidence of antidrug antibodies (ADA) to SBT6050 [2 years]
Parts 1 and 2
Progression free survival [2 years]
Parts 2, 4, and 5

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Duke University	Durham	North Carolina	United States	27708
3	University of Pittsburgh Medical Center Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
4	Sarah Cannon Research Institute/Tennessee Oncology	Nashville	Tennessee	United States	37203
5	MD Anderson Cancer Center	Houston	Texas	United States	77030
6	The START Center for Cancer Care	San Antonio	Texas	United States	78229
7	Macquarie University Hospital Clinical Trials Unit	Sydney	New South Wales	Australia	2109
8	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
9	Breast Cancer Research Centre - WA	Nedlands	Western Australia	Australia	6009
10	Seoul National University Hospital	Seoul		Korea, Republic of	03080
11	Asan Medical Center	Seoul		Korea, Republic of	05505
12	Samsung Medical Center	Seoul		Korea, Republic of	06351