Preventing Dato-DXd Associated Stomatitis With Dexamethasone Mouthwash, TROPION-DM

NCT06974604 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BrUOG 431
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

TROPION-DM/BrUOG-431 is a prospective, , phase 2 trial with two non-comparative cohorts analyzed jointly for primary endpoint in adult patients with either (Cohort 1:) advanced/metastatic hormone-receptor positive (\[HR+\], estrogen receptor and/or progesterone receptor positive) breast cancer (BC), or advanced/metastatic triple negative breast cancer (TNBC) or (Cohort 2:) advanced/metastatic non-squamous non-small cell lung cancer (NSCLC). All patients will be treated with Datopotumab deruxtecan (Dato-DXd) at 6 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity. Due to the risk of stomatitis, the investigational component of this trial will be to incorporate alcohol-free dexamethasone mouthwash, 10 mL 0.5 mg/5mL oral solution, days 1-5, swish and spit four times daily for the first 3 cycles.

Conditions

Breast Neoplasms; Lung Neoplasms

Keywords

Advanced/metastatic hormone-receptor positive [HR+], estrogen receptor and/or progesterone receptor positive; Advanced/metastatic triple negative breast cancer; Advanced/metastatic non-squamous, non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Lower the incidence of all stomatitis

  Lower the incidence of all stomatitis by 20%

  Approximately 9 weeks

Secondary Outcomes (1)

• Clinical benefit

  Approximately 9 weeks

Study Arms (1)

Dexamethasone 10mL

EXPERIMENTAL

Prophylactic oral dexamethasone

Drug: Dexamethasone oral

Interventions

Dexamethasone oral DRUG

Dexamethasone 10 mL daily for days 1-5 for each of the first 3 cycles of therapy Datopotamab Deruxtecan 6.0 mg/kg IV on day 1 every 21 days

Also known as: Datopotamab Deruxtecan (Dato-DXd DS-1062a)

Dexamethasone 10mL

Eligibility Criteria

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

You may qualify if:

• Has advanced and/or metastatic cancer that meets one of the following criteria:
• Pathologically documented unresectable advanced non-squamous NSCLC not amenable to curative therapy that has progressed on at least one prior therapy.
• Pathologically documented triple negative breast cancer (estrogen receptor negative and progesterone receptor negative and HER2 negative) who have progressed on at least 1 prior line of therapy or in the opinion of the treating physician, not be a candidate for standard first-line metastatic breast cancer therapy
• Pathologically documented hormone receptor positive breast cancer (estrogen receptor and/or progesterone receptor positive, HER2 negative) which has progressed on hormonal based therapy including CDK4/6 inhibitor and 1 prior line of chemotherapy and/or antibody drug conjugate therapy.
• Aged ≥18 years.
• Has an Eastern Cooperative Oncology Group performance status 0-2.
• Has a left ventricular ejection fraction (LVEF) 50% by either an echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 28 days before enrollment.
• Measurable disease based on Response Evaluation Criteria in Solids Tumors (RECIST) version 1.1.
• Has adequate organ function that would make them an appropriate candidate for Datopotamab deruxtecan therapy as treatment of advanced metastatic cancer as assessed by the treating physician, which shall include results of complete blood count with differential, and comprehensive metabolic panel within 14 days before Cycle 1, Day 1, defined as:
• Platelet count ≥100,000/mm3
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1000/mm3
• Creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation.
• Aspartate aminotransferase ≤3 ×ULN (if liver metastases are present, ≤5 × ULN)
• Alanine aminotransferase ≤3 × ULN (if liver metastases are present, ≤5 × ULN)

You may not qualify if:

• Active second malignancy which would alter interpretation of study results.
• Has a history of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has clinically significant corneal disease
• Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd.
• Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
• Has ongoing radiation-related toxicities
• Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
• Has active human immunodeficiency virus (HIV) infection that is not well controlled.
• Has an active or uncontrolled hepatitis B and/or hepatitis C infection
• Is lactating or pregnant as confirmed by pregnancy tests performed within 7 days before enrollment.
• Clinically severe pulmonary compromise resulting from autoimmune, connective tissue or inflammatory disorders with pulmonary involvement.
• Has uncontrolled or significant cardiac disease (including MI or unstable angina within the past 6 months, NYHA Class II-IV heart failure, uncontrolled hypertension, uncontrolled or significant arrhythmia).
• Patients with the following may be enrolled based on the investigator's/treating physician's assessment (documentation must be submitted to BrUOG). -Mean resting corrected QTcF interval \> 470 ms.
• History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
• Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.

Sponsors & Collaborators

• Brown University: lead
• Rhode Island Hospital: collaborator
• The Miriam Hospital: collaborator

Study Sites (1)

Rhode Island and the Miriam Hospitals (Brown University Health)

Providence, Rhode Island, 02903/02906, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Stephanie Graff, MD

  Rhode Island and the Miriam Hospitals (Brown University Health)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brown University Oncology Research Group (BrUOG)

CONTACT

401-863-3000; BrUOG@brown.edu

Stephanie Graff, MD

CONTACT

401-444-5388; Sgraff1@brownhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 16, 2025
• Study Start: October 22, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2029
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)