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

Phase 1

Terminated

• Conditions: HER2-positive Gastric Cancer; HER2-positive Breast Cancer; HER2-expressing Non-small Cell Lung Cancer; HER2-positive Colorectal Cancer
• Interventions: Drug: SBT6050; Drug: trastuzumab deruxtecan; Drug: tucatinib; Drug: trastuzumab; Drug: capecitabine

• Registration Number: NCT05091528
• Lead Sponsor: Silverback Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-10-12
• Study First Submitted QC: 2021-10-12
• Study First Posted: 2021-10-25
• Study Start: 2022-02-08
• Status Verified: 2022-07
• Primary Completion: 2022-07-07
• Study Completion: 2022-07-07
• Results First Submitted: 2022-07-18
• Results First Submitted QC: 2022-07-22
• Last Update Submitted: 2022-07-22
• Results First Posted: 2022-08-18
• Last Update Posted: 2022-08-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SBT6050 + T-DXd (6.4 mg/kg)	SBT6050	SBT6050 plus trastuzumab deruxtecan
SBT6050 + Tucatinib + Trastuzumab	SBT6050	SBT6050 plus tucatinib and trastuzumab
SBT6050 + T-DXd (5.4 mg/kg)	SBT6050	SBT6050 plus trastuzumab deruxtecan
SBT6050 + Tucatinib + Trastuzumab + Capecitabine	SBT6050	SBT6050 plus tucatinib, trastuzumab, and capecitabine
SBT6050 + T-DXd (5.4 mg/kg)	trastuzumab deruxtecan	SBT6050 plus trastuzumab deruxtecan
SBT6050 + T-DXd (6.4 mg/kg)	trastuzumab deruxtecan	SBT6050 plus trastuzumab deruxtecan
SBT6050 + Tucatinib + Trastuzumab + Capecitabine	trastuzumab	SBT6050 plus tucatinib, trastuzumab, and capecitabine
SBT6050 + Tucatinib + Trastuzumab + Capecitabine	tucatinib	SBT6050 plus tucatinib, trastuzumab, and capecitabine
SBT6050 + Tucatinib + Trastuzumab + Capecitabine	capecitabine	SBT6050 plus tucatinib, trastuzumab, and capecitabine
SBT6050 + Tucatinib + Trastuzumab	tucatinib	SBT6050 plus tucatinib and trastuzumab
SBT6050 + Tucatinib + Trastuzumab	trastuzumab	SBT6050 plus tucatinib and trastuzumab

Primary Outcome Measures

Name	Time	Method
Number of Participants With an Objective Response Rate	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.
Proportion of Participants With Dose Limiting Toxicities	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.
Number of Participants With Treatment-emergent Adverse Events	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.
Number of Participants With Laboratory Abnormalities	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events	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.
Proportion of Participants With Clinical Benefit Rate	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.
Duration of Response for Participants With an Objective Response Rate	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.
Number of Participants With an Objective Response Rate	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.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States