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

HER2-positive Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05091528
• Other study ID #: SBT6050-201
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 8, 2022
• Est. completion date: July 7, 2022

Study information

• Verified date: July 2022
• Source: Silverback Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: July 7, 2022
• Est. primary completion date: July 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Colorectal Neoplasms
• HER2-positive Breast Cancer
• HER2-positive Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• SBT6050
Dose range of 0.45 to 0.6 mg/kg by subcutaneous (SC) injection in 21-day cycles
• trastuzumab deruxtecan
5.4 mg/kg by intravenous (IV) infusion in 21-day cycles
• tucatinib
300 mg by mouth (PO) twice daily (BID)
• trastuzumab
8 mg/kg loading dose (first dose), then 6 mg/kg maintenance dose (subsequent doses) IV infusion in 21-day cycles
• capecitabine
1000 mg/m2 PO BID for 14 days of each 21-day cycle
• trastuzumab deruxtecan
6.4 mg/kg by IV infusion in 21-day cycles

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Silverback Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	21 days
Primary	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.	18 weeks
Primary	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.	18 weeks
Primary	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.	0 weeks
Secondary	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.	0 weeks
Secondary	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.	18 weeks
Secondary	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.	0 weeks
Secondary	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.	0 weeks