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

• Sponsor: Silverback Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT05091528
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 4
• Actual Duration (Months): 4.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HER2-positive Breast Cancer; HER2-positive Gastric Cancer; HER2-positive Colorectal Cancer; HER2-expressing Non-small Cell Lung Cancer	Drug: SBT6050; Drug: trastuzumab deruxtecan; Drug: tucatinib; Drug: trastuzumab; Drug: capecitabine; Drug: trastuzumab deruxtecan	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 8, 2022
• Actual Primary Completion Date: Jul 7, 2022
• Actual Study Completion Date: Jul 7, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Silverback Therapeutics

Investigators

• Study Director: Naomi Hunder, MD, Silverback Therapeutics, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 12, 2022

More Information

Publications

None provided.

• Responsible Party: Silverback Therapeutics
• ClinicalTrials.gov Identifier: NCT05091528
• Other Study ID Numbers: SBT6050-201
• First Posted: Oct 25, 2021
• Last Update Posted: Aug 18, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Silverback Therapeutics: SBT6050; HER2; breast cancer; gastric cancer; colorectal cancer; non-small cell lung cancer; TLR8; trastuzumab deruxtecan; tucatinib; trastuzumab; capecitabine
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Stomach Neoplasms; Capecitabine; Trastuzumab; Tucatinib

Study Results

Participant Flow

Arm/Group Title	SBT6050 + T-DXd (5.4 mg/kg)	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab + Capecitabine	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	SBT6050 plus trastuzumab deruxtecan 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	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	SBT6050 plus tucatinib, trastuzumab, and capecitabine SBT6050: Dose range of 0.45 to 0.6 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 capecitabine: 1000 mg/m2 PO BID for 14 days of each 21-day cycle	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
Period Title: Overall Study
STARTED	0	1	0	1
COMPLETED	0	0	0	0
NOT COMPLETED	0	1	0	1

Baseline Characteristics

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	1	1	2
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	1 100%	1 50%
>=65 years	1 100%	0 0%	1 50%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	1 100%	2 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 100%	1 100%	2 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%
Primary Tumor Type (Count of Participants)
Gastric cancer	1 100%	0 0%	1 50%
Colorectal cancer	0 0%	1 100%	1 50%
Prior Therapy Regimens (Number of therapy regimens) [Number]
Number [Number of therapy regimens]	1	1	2

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Dose Limiting Toxicities
Description	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

Outcome Measure Data

Analysis Population Description

Participants who were enrolled and treated with at least 1 dose of SBT6050.

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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	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
Measure Participants	1	1
Count of Participants [Participants]	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

Participants who were enrolled and treated with at least 1 dose of SBT6050.

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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	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
Measure Participants	1	1
Count of Participants [Participants]	1 100%	1 100%

3. Primary Outcome

Title	Number of Participants With Laboratory Abnormalities
Description	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

Outcome Measure Data

Analysis Population Description

Participants who were enrolled and treated with at least 1 dose of SBT6050.

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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	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
Measure Participants	1	1
Count of Participants [Participants]	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants With an Objective Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

No participants were enrolled in the dose expansion cohorts; study was terminated by Sponsor.

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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	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
Measure Participants	0	0

5. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

No participants were enrolled in the dose expansion cohorts; study was terminated by Sponsor.

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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	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
Measure Participants	0	0

6. Secondary Outcome

Title	Number of Participants With an Objective Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

Participants who were enrolled and treated with at least 1 dose of SBT6050.

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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	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
Measure Participants	1	1
Count of Participants [Participants]	1 100%	0 0%

7. Secondary Outcome

Title	Duration of Response for Participants With an Objective Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

Data not captured; study was terminated by Sponsor.

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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	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
Measure Participants	0	0

8. Secondary Outcome

Title	Proportion of Participants With Clinical Benefit Rate
Description	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

Outcome Measure Data

Analysis Population Description

No participants were enrolled in the dose expansion cohorts; study was terminated by Sponsor.

Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)	SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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	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
Measure Participants	0	0

Adverse Events

Time Frame	18 weeks
Arm/Group Title	SBT6050 + T-DXd (6.4 mg/kg)		SBT6050 + Tucatinib + Trastuzumab
Arm/Group Description	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		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
All Cause Mortality
	SBT6050 + T-DXd (6.4 mg/kg)		SBT6050 + Tucatinib + Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Serious Adverse Events
	SBT6050 + T-DXd (6.4 mg/kg)		SBT6050 + Tucatinib + Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	SBT6050 + T-DXd (6.4 mg/kg)		SBT6050 + Tucatinib + Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)
Gastrointestinal disorders
Bloating	1/1 (100%)		0/1 (0%)
Constipation	0/1 (0%)		1/1 (100%)
General disorders
Fatigue	1/1 (100%)		0/1 (0%)
Injection site reaction	1/1 (100%)		1/1 (100%)
Immune system disorders
Cytokine release syndrome	1/1 (100%)		0/1 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/1 (100%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia	1/1 (100%)		0/1 (0%)

Limitations/Caveats

Early termination leading to small numbers of participants analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.