HER2-expressing Non-small Cell Lung Cancer, HER2-positive Breast Cancer, HER2-positive Colorectal Cancer, HER2-positive Gastric Cancer
Conditions
Keywords
SBT6050, HER2, breast cancer, gastric cancer, colorectal cancer, non-small cell lung cancer, TLR8, trastuzumab deruxtecan, tucatinib, trastuzumab, capecitabine
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.
Interventions
DRUGSBT6050
Dose range of 0.45 to 0.6 mg/kg by subcutaneous (SC) injection in 21-day cycles
DRUGtrastuzumab deruxtecan
5.4 mg/kg by intravenous (IV) infusion in 21-day cycles
DRUGtucatinib
300 mg by mouth (PO) twice daily (BID)
DRUGtrastuzumab
8 mg/kg loading dose (first dose), then 6 mg/kg maintenance dose (subsequent doses) IV infusion in 21-day cycles
DRUGcapecitabine
1000 mg/m2 PO BID for 14 days of each 21-day cycle
Sponsors
Silverback Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SBT6050 + T-DXd (6.4 mg/kg) SBT6050 plus trastuzumab deruxtecan
SBT6050: Dosed with 0.45 mg/kg by subcutaneous (SC) injection in 21-day cycles
trastuzumab deruxtecan: 6.4 mg/kg by IV infusion in 21-day cycles | 1 |
| SBT6050 + Tucatinib + Trastuzumab SBT6050 plus tucatinib and trastuzumab
SBT6050: Dosed with 0.45 mg/kg by subcutaneous (SC) injection 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 | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Study Termination by Sponsor | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | SBT6050 + T-DXd (6.4 mg/kg) | Total | SBT6050 + Tucatinib + Trastuzumab |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Primary Tumor Type Colorectal cancer | 0 Participants | 1 Participants | 1 Participants |
| Primary Tumor Type Gastric cancer | 1 Participants | 1 Participants | 0 Participants |
| Prior Therapy Regimens | 1 Number of therapy regimens | 2 Number of therapy regimens | 1 Number of therapy regimens |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
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.
Time frame: 0 weeks
Population: No participants were enrolled in the dose expansion cohorts; study was terminated by Sponsor.
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.
Time frame: 18 weeks
Population: Participants who were enrolled and treated with at least 1 dose of SBT6050.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SBT6050 + T-DXd (6.4 mg/kg) | Number of Participants With Laboratory Abnormalities | 0 Participants |
| SBT6050 + Tucatinib + Trastuzumab | Number of Participants With Laboratory Abnormalities | 0 Participants |
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.
Time frame: 18 weeks
Population: Participants who were enrolled and treated with at least 1 dose of SBT6050.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SBT6050 + T-DXd (6.4 mg/kg) | Number of Participants With Treatment-emergent Adverse Events | 1 Participants |
| SBT6050 + Tucatinib + Trastuzumab | Number of Participants With Treatment-emergent Adverse Events | 1 Participants |
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.
Time frame: 21 days
Population: Participants who were enrolled and treated with at least 1 dose of SBT6050.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SBT6050 + T-DXd (6.4 mg/kg) | Proportion of Participants With Dose Limiting Toxicities | 0 Participants |
| SBT6050 + Tucatinib + Trastuzumab | Proportion of Participants With Dose Limiting Toxicities | 0 Participants |
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.
Time frame: 0 weeks
Population: Data not captured; study was terminated by Sponsor.
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.
Time frame: 18 weeks
Population: Participants who were enrolled and treated with at least 1 dose of SBT6050.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SBT6050 + T-DXd (6.4 mg/kg) | Number of Participants With an Objective Response Rate | 1 Participants |
| SBT6050 + Tucatinib + Trastuzumab | Number of Participants With an Objective Response Rate | 0 Participants |
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.
Time frame: 0 weeks
Population: No participants were enrolled in the dose expansion cohorts; study was terminated by Sponsor.
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.
Time frame: 0 weeks
Population: No participants were enrolled in the dose expansion cohorts; study was terminated by Sponsor.