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

NCT05091528 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: SBT6050-201
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (4)

• Number of Participants With Treatment-emergent Adverse Events

  0 weeks

• Number of Participants With an Objective Response Rate

  18 weeks

• Duration of Response for Participants With an Objective Response Rate

  0 weeks

• Proportion of Participants With Clinical Benefit Rate

  0 weeks

Study Arms (4)

SBT6050 + T-DXd (5.4 mg/kg)

EXPERIMENTAL

SBT6050 plus trastuzumab deruxtecan

Drug: SBT6050; Drug: trastuzumab deruxtecan

SBT6050 + T-DXd (6.4 mg/kg)

EXPERIMENTAL

SBT6050 plus trastuzumab deruxtecan

Drug: SBT6050; Drug: trastuzumab deruxtecan

SBT6050 + Tucatinib + Trastuzumab + Capecitabine

EXPERIMENTAL

SBT6050 plus tucatinib, trastuzumab, and capecitabine

Drug: SBT6050; Drug: tucatinib; Drug: trastuzumab; Drug: capecitabine

SBT6050 + Tucatinib + Trastuzumab

EXPERIMENTAL

SBT6050 plus tucatinib and trastuzumab

Drug: SBT6050; Drug: tucatinib; Drug: trastuzumab

Interventions

SBT6050 DRUG

Dose range of 0.45 to 0.6 mg/kg by subcutaneous (SC) injection in 21-day cycles

SBT6050 + T-DXd (5.4 mg/kg); SBT6050 + T-DXd (6.4 mg/kg); SBT6050 + Tucatinib + Trastuzumab; SBT6050 + Tucatinib + Trastuzumab + Capecitabine

trastuzumab deruxtecan DRUG

5.4 mg/kg by intravenous (IV) infusion in 21-day cycles

Also known as: ENHERTU

SBT6050 + T-DXd (5.4 mg/kg)

tucatinib DRUG

300 mg by mouth (PO) twice daily (BID)

Also known as: TUKYSA

SBT6050 + Tucatinib + Trastuzumab; SBT6050 + Tucatinib + Trastuzumab + Capecitabine

trastuzumab DRUG

8 mg/kg loading dose (first dose), then 6 mg/kg maintenance dose (subsequent doses) IV infusion in 21-day cycles

Also known as: HERCEPTIN

SBT6050 + Tucatinib + Trastuzumab; SBT6050 + Tucatinib + Trastuzumab + Capecitabine

capecitabine DRUG

1000 mg/m2 PO BID for 14 days of each 21-day cycle

Also known as: XELODA

SBT6050 + Tucatinib + Trastuzumab + Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Silverback Therapeutics: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Stomach Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

trastuzumab deruxtecan; tucatinib; Trastuzumab; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Early termination leading to small numbers of participants analyzed.

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Silverback Therapeutics, Inc.

info@silverbacktx.com

206-456-2900

Study Officials

• Naomi Hunder, MD

  Silverback Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: October 25, 2021
• Study Start: February 8, 2022
• Primary Completion: July 7, 2022
• Study Completion: July 7, 2022
• Last Updated: August 18, 2022
• Results First Posted: August 18, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)