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

July 22, 2022 updated by: Silverback Therapeutics

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: SBT6050 + T-DXd (5.4 mg/kg)
SBT6050 plus trastuzumab deruxtecan
Drug: SBT6050
Dose range of 0.45 to 0.6 mg/kg by subcutaneous (SC) injection in 21-day cycles
Drug: trastuzumab deruxtecan
5.4 mg/kg by intravenous (IV) infusion in 21-day cycles
Other Names:
  • ENHERTU
Drug: trastuzumab deruxtecan
6.4 mg/kg by IV infusion in 21-day cycles
Other Names:
  • ENHERTU
EXPERIMENTAL: SBT6050 + T-DXd (6.4 mg/kg)
SBT6050 plus trastuzumab deruxtecan
Drug: SBT6050
Dose range of 0.45 to 0.6 mg/kg by subcutaneous (SC) injection in 21-day cycles
Drug: trastuzumab deruxtecan
5.4 mg/kg by intravenous (IV) infusion in 21-day cycles
Other Names:
  • ENHERTU
Drug: trastuzumab deruxtecan
6.4 mg/kg by IV infusion in 21-day cycles
Other Names:
  • ENHERTU
EXPERIMENTAL: SBT6050 + Tucatinib + Trastuzumab + Capecitabine
SBT6050 plus tucatinib, trastuzumab, and capecitabine
Drug: SBT6050
Dose range of 0.45 to 0.6 mg/kg by subcutaneous (SC) injection in 21-day cycles
Drug: tucatinib
300 mg by mouth (PO) twice daily (BID)
Other Names:
  • TUKYSA
Drug: trastuzumab
8 mg/kg loading dose (first dose), then 6 mg/kg maintenance dose (subsequent doses) IV infusion in 21-day cycles
Other Names:
  • HERCEPTIN
Drug: capecitabine
1000 mg/m2 PO BID for 14 days of each 21-day cycle
Other Names:
  • XELODA
EXPERIMENTAL: SBT6050 + Tucatinib + Trastuzumab
SBT6050 plus tucatinib and trastuzumab
Drug: SBT6050
Dose range of 0.45 to 0.6 mg/kg by subcutaneous (SC) injection in 21-day cycles
Drug: tucatinib
300 mg by mouth (PO) twice daily (BID)
Other Names:
  • TUKYSA
Drug: trastuzumab
8 mg/kg loading dose (first dose), then 6 mg/kg maintenance dose (subsequent doses) IV infusion in 21-day cycles
Other Names:
  • HERCEPTIN

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants With Dose Limiting Toxicities
Time Frame: 21 days
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.
21 days
Number of Participants With Treatment-emergent Adverse Events
Time Frame: 18 weeks
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.
18 weeks
Number of Participants With Laboratory Abnormalities
Time Frame: 18 weeks
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.
18 weeks
Number of Participants With an Objective Response Rate
Time Frame: 0 weeks
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.
0 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events
Time Frame: 0 weeks
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.
0 weeks
Number of Participants With an Objective Response Rate
Time Frame: 18 weeks
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.
18 weeks
Duration of Response for Participants With an Objective Response Rate
Time Frame: 0 weeks
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.
0 weeks
Proportion of Participants With Clinical Benefit Rate
Time Frame: 0 weeks
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.
0 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Silverback Therapeutics

Investigators

  • Study Director: Naomi Hunder, MD, Silverback Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 8, 2022

Primary Completion (ACTUAL)

July 7, 2022

Study Completion (ACTUAL)

July 7, 2022

Study Registration Dates

First Submitted

October 12, 2021

First Submitted That Met QC Criteria

October 12, 2021

First Posted (ACTUAL)

October 25, 2021

Study Record Updates

Last Update Posted (ACTUAL)

August 18, 2022

Last Update Submitted That Met QC Criteria

July 22, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SBT6050-201

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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