Testing the Biological Effects of DS-8201a on Patients With Advanced Cancer

NCT04294628 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: NCI-2020-0120620-C-0154P19468810346
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 6

Brief Summary

This phase I trial studies the biological effects of DS-8201a on patients with HER2 positive cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). DS-8201a works by binding to a protein called HER2 that is present on the surface of tumor cells. This allows DS-8201a to kill the tumor cells by damaging their deoxyribonucleic acid (DNA), resulting in tumor cell death. This study looks at how DS-8201a may affect the levels of certain proteins and immune cells in tumors and how well the drug works against tumor cells by examining cells from a small piece tumor taken before and after DS-8201a is given.

Conditions

Advanced Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; Refractory Malignant Solid Neoplasm; Unresectable Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Total topoisomerase 1 (Top1)

  Up to day 1 of cycle 3 (each cycle is 21 days) or optionally, up to time of disease progression or restaging follow-up

• Tumor immune microenvironment response

  Tumor-adjacent CD8+, CD3ζ pY142+ cells/mm\^2 .

  Up to day 1 of cycle 3 (each cycle is 21 days) or optionally, up to time of disease progression or restaging follow-up

Secondary Outcomes (3)

• Association between serum concentrations of DS-8201a and total Top1 levels in tumor biopsies

  Up to day 1 of cycle 3 (each cycle is 21 days) or optionally, up to time of disease progression or restaging follow-up

• Incidence of adverse events

  Up to 30 days post-treatment

• Overall response rate

  From the start of the treatment until disease progression/recurrence

Study Arms (1)

Treatment (trastuzumab deruxtecan)

EXPERIMENTAL

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, CT or MRI, biopsies, and collection of blood samples throughout the study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Biological: Trastuzumab Deruxtecan

Interventions

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (trastuzumab deruxtecan)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (trastuzumab deruxtecan)

Trastuzumab Deruxtecan BIOLOGICAL

Given IV

Also known as: DS-8201, DS-8201a, Enhertu, Fam-trastuzumab Deruxtecan-nxki, T-DXd, WHO 10516

Treatment (trastuzumab deruxtecan)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (trastuzumab deruxtecan)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (trastuzumab deruxtecan)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (trastuzumab deruxtecan)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (trastuzumab deruxtecan)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• Patients must have measurable or evaluable disease
• Age \>= 18 years of age
• Patients must have HER2-positive or HER2-expressing tumors as defined by Clinical Laboratory Improvement Act (CLIA)-certified labs. Patients must have either:
• A tumor HER2 immunohistochemistry (IHC) score of 1+ or greater (as determined by a CLIA-certified IHC test, per criteria specified) or
• A tumor with HER2 amplification (as determined by CLIA-certified in situ hybridization \[ISH\] or a CLIA-certified next-generation sequencing assay)
• Patients with HER2 mutations are eligible, as are patients with HER2-positive breast cancer
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Absolute neutrophil count \>= 1,500/mcL (within 8 days of enrollment)
• Platelets \>= 100,000/mcL (within 8 days of enrollment)
• Leukocytes \>= 3,000/mcL (within 8 days of enrollment)
• Hemoglobin \>= 9 g/dL (\>= 8.0 g/dL for gastric cancer \[GC\] only) (within 8 days of enrollment)
• Serum albumin \>= 2.5 g/dL (GC only) (within 8 days of enrollment)
• Total bilirubin =\< 1.5 x institutional upper limit of normal (=\< 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline) (within 8 days of enrollment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal OR =\< 5 x institutional upper limit of normal for patients with liver metastases at baseline (within 8 days of enrollment)

You may not qualify if:

• Patients who have had:
• Chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer-with the exception of standard of care androgen deprivation treatment) within:
• weeks or five half-lives, whichever is shorter, for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents, weekly paclitaxel or
• weeks for nitrosoureas or mitomycin C or
• Immunotherapy, including monoclonal antibody therapy, within 4 weeks
• Patients with any of the following pulmonary-related illnesses:
• A history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or for whom suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\] grade 3-4 per Global Initiative for Obstructive Lung Disease \[GOLD\] criteria, restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy
• Patients who have had radiation therapy within 4 weeks (or palliative stereotactic radiation therapy within 2 weeks)
• Patients who have had a major surgery within 4 weeks
• Patients who are receiving any other investigational agents
• Patients with a medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association class II to IV), or with troponin levels consistent with myocardial infarction (as defined according to the assay manufacturer) 28 days prior to enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to DS-8201a (e.g., other topoisomerase I inhibitors) or the inactive ingredients in the drug product
• Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies
• Patients with a Fridericia's formula-corrected QT interval (QTcF) prolongation to \> 470 ms (females) or \> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Sarah Shin

  National Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 4, 2020
• Study Start: September 1, 2020
• Primary Completion: September 2, 2025
• Study Completion (Estimated): January 19, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (6)