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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Colorectal Cancer, HER2-expressing Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: SBT6050
* Drug: trastuzumab deruxtecan
* Drug: tucatinib
* Drug: trastuzumab
* Drug: capecitabine
* Drug: trastuzumab deruxtecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SBT6050, HER2, breast cancer, gastric cancer, colorectal cancer, non-small cell lung cancer, TLR8, trastuzumab deruxtecan, tucatinib, trastuzumab, capecitabine