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A Safety and Activity Study of SBT6050 in Combination With Other HER2-directed Therapies for HER2-positive Cancers

Primary Purpose

HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Colorectal Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SBT6050
trastuzumab deruxtecan
tucatinib
trastuzumab
capecitabine
trastuzumab deruxtecan
Sponsored by
Silverback Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER2-positive Breast Cancer focused on measuring SBT6050, HER2, breast cancer, gastric cancer, colorectal cancer, non-small cell lung cancer, TLR8, trastuzumab deruxtecan, tucatinib, trastuzumab, capecitabine

Eligibility Criteria

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

Inclusion Criteria:

  • Advanced or metastatic HER2-expressing (IHC 2+ or 3+) or HER2-amplified solid tumors
  • Measurable disease per the the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria

  • Tumor lesion amenable for biopsy or able to submit an adequate recent archived tumor tissue for baseline testing, as follows:

    1. Breast cancer and colorectal cancer (CRC): archival biopsy tissue obtained after the last HER2-directed therapy (excluding trastuzumab and pertuzumab), or a fresh biopsy
    2. Gastric cancer and non-small-cell lung cancer (NSCLC): archival biopsy tissue taken within the past 12 months and after completion of last HER2-directed therapy, or a fresh biopsy
  • ECOG Performance Status of 0 or 1
  • Adequate hematologic, hepatic, renal, and cardiac function

Exclusion Criteria:

  • History of allergic reactions to certain components of study treatment therapies
  • Untreated brain metastases
  • Currently active (or history of) autoimmune disease
  • Taking the equivalent of >10 mg / day of prednisone
  • Taking a medication that moderately induces CYP2C, strongly inhibits CYP2C8, or interacts with both enzymes (CYP3A and CYP2C8)
  • Uncontrolled or clinically significant interstitial lung disease (ILD) / pneumonitis that requires systemic corticosteroid treatment or suspected ILD / pneumonitis
  • HIV infection, active hepatitis B or hepatitis C infection

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

SBT6050 + T-DXd (5.4 mg/kg)

SBT6050 + T-DXd (6.4 mg/kg)

SBT6050 + Tucatinib + Trastuzumab + Capecitabine

SBT6050 + Tucatinib + Trastuzumab

Arm Description

SBT6050 plus trastuzumab deruxtecan

SBT6050 plus trastuzumab deruxtecan

SBT6050 plus tucatinib, trastuzumab, and capecitabine

SBT6050 plus tucatinib and trastuzumab

Outcomes

Primary Outcome Measures

Proportion of Participants With Dose Limiting Toxicities
Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. This outcome measure applies only to participants in the dose escalation cohorts.
Number of Participants With Treatment-emergent Adverse Events
Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. This outcome measure applies only to participants in the dose escalation cohorts.
Number of Participants With Laboratory Abnormalities
Clinically significant treatment-emergent laboratory abnormalities as assessed by the NCI CTCAE Version 5.0. This outcome measure applies only to participants in the dose escalation cohorts.
Number of Participants With an Objective Response Rate
Complete response and partial response as assessed by RECIST Version 1.1 Criteria. This outcome measure applies only to participants in the dose expansion cohorts.

Secondary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events
Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. This outcome measure applies only to participants in the dose expansion cohorts.
Number of Participants With an Objective Response Rate
Complete response and partial response as assessed by RECIST Version 1.1 Criteria. This outcome measure applies only to participants in the dose escalation cohorts.
Duration of Response for Participants With an Objective Response Rate
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. This outcome measure applies to all participants.
Proportion of Participants With Clinical Benefit Rate
Complete response, partial response, or durable stable disease as assessed by RECIST Version 1.1 Criteria. This outcome measure applied only to participants in the dose expansion cohorts.

Full Information

First Posted
October 12, 2021
Last Updated
July 22, 2022
Sponsor
Silverback Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05091528
Brief Title
A Safety and Activity Study of SBT6050 in Combination With Other HER2-directed Therapies for HER2-positive Cancers
Official Title
An Open-label, Phase 1/2, Dose-escalation and Expansion Study of SBT6050 Combined With Other HER2-directed Therapies in Subjects With Pretreated Unresectable Locally Advanced and/or Metastatic HER2-expressing or HER2-amplified Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision based on strategic re-alignment
Study Start Date
February 8, 2022 (Actual)
Primary Completion Date
July 7, 2022 (Actual)
Study Completion Date
July 7, 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
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is designed to assess the safety and preliminary activity of SBT6050 in combination with trastuzumab deruxtecan (Part 1) or tucatinib plus trastuzumab +/- capecitabine (Part 2). Participants will be enrolled into each Arm based on cancer diagnosis and prior therapies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Colorectal Cancer, HER2-expressing Non-small Cell Lung Cancer
Keywords
SBT6050, HER2, breast cancer, gastric cancer, colorectal cancer, non-small cell lung cancer, TLR8, trastuzumab deruxtecan, tucatinib, trastuzumab, capecitabine

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
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SBT6050 + T-DXd (5.4 mg/kg)
Arm Type
Experimental
Arm Description
SBT6050 plus trastuzumab deruxtecan
Arm Title
SBT6050 + T-DXd (6.4 mg/kg)
Arm Type
Experimental
Arm Description
SBT6050 plus trastuzumab deruxtecan
Arm Title
SBT6050 + Tucatinib + Trastuzumab + Capecitabine
Arm Type
Experimental
Arm Description
SBT6050 plus tucatinib, trastuzumab, and capecitabine
Arm Title
SBT6050 + Tucatinib + Trastuzumab
Arm Type
Experimental
Arm Description
SBT6050 plus tucatinib and trastuzumab
Intervention Type
Drug
Intervention Name(s)
SBT6050
Intervention Description
Dose range of 0.45 to 0.6 mg/kg by subcutaneous (SC) injection in 21-day cycles
Intervention Type
Drug
Intervention Name(s)
trastuzumab deruxtecan
Other Intervention Name(s)
ENHERTU
Intervention Description
5.4 mg/kg by intravenous (IV) infusion in 21-day cycles
Intervention Type
Drug
Intervention Name(s)
tucatinib
Other Intervention Name(s)
TUKYSA
Intervention Description
300 mg by mouth (PO) twice daily (BID)
Intervention Type
Drug
Intervention Name(s)
trastuzumab
Other Intervention Name(s)
HERCEPTIN
Intervention Description
8 mg/kg loading dose (first dose), then 6 mg/kg maintenance dose (subsequent doses) IV infusion in 21-day cycles
Intervention Type
Drug
Intervention Name(s)
capecitabine
Other Intervention Name(s)
XELODA
Intervention Description
1000 mg/m2 PO BID for 14 days of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
trastuzumab deruxtecan
Other Intervention Name(s)
ENHERTU
Intervention Description
6.4 mg/kg by IV infusion in 21-day cycles
Primary Outcome Measure Information:
Title
Proportion of Participants With Dose Limiting Toxicities
Description
Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. This outcome measure applies only to participants in the dose escalation cohorts.
Time Frame
21 days
Title
Number of Participants With Treatment-emergent Adverse Events
Description
Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. This outcome measure applies only to participants in the dose escalation cohorts.
Time Frame
18 weeks
Title
Number of Participants With Laboratory Abnormalities
Description
Clinically significant treatment-emergent laboratory abnormalities as assessed by the NCI CTCAE Version 5.0. This outcome measure applies only to participants in the dose escalation cohorts.
Time Frame
18 weeks
Title
Number of Participants With an Objective Response Rate
Description
Complete response and partial response as assessed by RECIST Version 1.1 Criteria. This outcome measure applies only to participants in the dose expansion cohorts.
Time Frame
0 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events
Description
Severity of treatment-emergent adverse events as assessed by the NCI CTCAE Version 5.0. This outcome measure applies only to participants in the dose expansion cohorts.
Time Frame
0 weeks
Title
Number of Participants With an Objective Response Rate
Description
Complete response and partial response as assessed by RECIST Version 1.1 Criteria. This outcome measure applies only to participants in the dose escalation cohorts.
Time Frame
18 weeks
Title
Duration of Response for Participants With an Objective Response Rate
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. This outcome measure applies to all participants.
Time Frame
0 weeks
Title
Proportion of Participants With Clinical Benefit Rate
Description
Complete response, partial response, or durable stable disease as assessed by RECIST Version 1.1 Criteria. This outcome measure applied only to participants in the dose expansion cohorts.
Time Frame
0 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Advanced or metastatic HER2-expressing (IHC 2+ or 3+) or HER2-amplified solid tumors Measurable disease per the the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria Tumor lesion amenable for biopsy or able to submit an adequate recent archived tumor tissue for baseline testing, as follows: Breast cancer and colorectal cancer (CRC): archival biopsy tissue obtained after the last HER2-directed therapy (excluding trastuzumab and pertuzumab), or a fresh biopsy Gastric cancer and non-small-cell lung cancer (NSCLC): archival biopsy tissue taken within the past 12 months and after completion of last HER2-directed therapy, or a fresh biopsy ECOG Performance Status of 0 or 1 Adequate hematologic, hepatic, renal, and cardiac function Exclusion Criteria: History of allergic reactions to certain components of study treatment therapies Untreated brain metastases Currently active (or history of) autoimmune disease Taking the equivalent of >10 mg / day of prednisone Taking a medication that moderately induces CYP2C, strongly inhibits CYP2C8, or interacts with both enzymes (CYP3A and CYP2C8) Uncontrolled or clinically significant interstitial lung disease (ILD) / pneumonitis that requires systemic corticosteroid treatment or suspected ILD / pneumonitis HIV infection, active hepatitis B or hepatitis C infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naomi Hunder, MD
Organizational Affiliation
Silverback Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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A Safety and Activity Study of SBT6050 in Combination With Other HER2-directed Therapies for HER2-positive Cancers

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