Clinical trial NCT05091528: A Safety and Activity Study of SBT6050 in Combination With Other HER2-directed Therapies for HER2-positive Cancers
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Silverback Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-10-25
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Participants With Dose Limiting Toxicities
timeFrame: 21 days
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: 18 weeks
measure: Number of Participants With Laboratory Abnormalities
timeFrame: 18 weeks
measure: Number of Participants With an Objective Response Rate
timeFrame: 0 weeks
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: 0 weeks
measure: Number of Participants With an Objective Response Rate
timeFrame: 18 weeks
measure: Duration of Response for Participants With an Objective Response Rate
timeFrame: 0 weeks
measure: Proportion of Participants With Clinical Benefit Rate
timeFrame: 0 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Silverback Therapeutics, Inc.
name: Naomi Hunder, MD
role: STUDY_DIRECTOR
References: