An Open-label, Single-arm Study of Prophylaxis for Datopotamab Deruxtecan (Dato-DXd) -Related Stomatitis in Eligible Patients With Metastatic or Inoperable Locally Recurrent Breast Cancer or Locally Advanced or Metastatic Epidermal Growth Factor Receptor-Mutated Non-small Cell Lung Cancer.

NCT07357597 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: D926UL00001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 20

Brief Summary

This is a multicenter, open-label, single-arm study of prophylaxis for Dato-DXd-related stomatitis in eligible patients with metastatic or inoperable locally recurrent breast cancer or locally advanced or metastatic Epidermal Growth Factor Receptor-Mutated (EGFRm) non-small cell lung cancer.

Conditions

Stomatitis

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of Dato-DXd treatment-emergent grade ≥ 2 stomatitis in patients receiving prophylactic dexamethasone mouthwash within first 12 weeks of study treatment

  Incidence is defined as the proportion of participants who develop National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 grade ≥ 2 stomatitis accompanied by either a Normalcy of Diet Subscale score ≤ 50 and/or a Numeric Rating Scale (NRS) oral-pain score of 7 on 2 consecutive days or 8, 9, or 10 on any one day. Severity will be based on the highest NCI-CTCAE v5.0 grade of stomatitis experienced by each participant. CTCAE displays Grades 1-5 with descriptions of severity for each adverse event (AE). Grade 1 for mild symptoms and Grade 5 for death related to AE. The Normalcy of Diet Subscale assesses the degree to which a patient can eat a normal diet and drink liquids. The scale is a ranking of 10 food categories, from easy-to-eat to difficult-to-eat. The Numeric Rating Scale is a scale for self-reporting of pain. Scores range from 0-10, with higher scores meaning the worst pain possible (0=no pain to 10=worst possible pain).

  From date of first dose of study treatment until 12 weeks after date of first dose of study treatment

Secondary Outcomes (7)

• Incidence and severity of Dato-DXd treatment-emergent grade ≥ 2 stomatitis

  From date of first dose of study treatment until 6 and 9 weeks after date of first dose of study treatment

• Incidence and severity of treatment-emergent stomatitis overall, by maximum CTCAE grade, and CTCAE grade ≥ 2

  From date of first dose of study treatment until 6, 9 and 12 weeks after date of first dose of study treatment

• Time to onset of grade ≥ 2 stomatitis

  From date of first dose until earliest of diagnosis of grade ≥2 stomatitis, Dato-DXD discontinuation and death, whichever occurs first, assessed up to approximately 21 months

• Time to resolution of Dato-DXd-related grade ≥ 2 stomatitis

  From date of diagnosis of grade ≥2 stomatitis until the earliest date of event resolved or reduced in severity to grade 1, assessed up to approximately 21 months

• Proportion of participants with a dose modification for Dato-DXd due to stomatitis

  From date of first dose until earliest of Dato-DXD discontinuation and death, assessed up to approximately 21 months

Study Arms (1)

Dexamethasone 0.5 mg/5 mL Mouthwash

EXPERIMENTAL

Participants will use dexamethasone 0.5 mg/5 mL alcohol-free mouthwash (10 mL, 4 times daily, swish for approximately 2 minutes, then spit out without swallowing). Participants will remain without food or drink for at least 30 minutes after use of dexamethasone

Drug: Dexamethasone mouthwash; Drug: Datopotamab Deruxtecan (Dato-DXd)

Interventions

Dexamethasone mouthwash DRUG

Dexamethasone steroid-based oral solution, comprised of 0.5 milligrams per 5mL of alcohol-free dexamethasone.

Dexamethasone 0.5 mg/5 mL Mouthwash

Datopotamab Deruxtecan (Dato-DXd) DRUG

Commercially available Dato-DXd is prescribed and administered to participants according to standard of care

Also known as: Datroway

Dexamethasone 0.5 mg/5 mL Mouthwash

Eligibility Criteria

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

You may qualify if:

• Patients are eligible to be included in the study only if all the following criteria apply:
• Disease Characteristics
• Patients with any of the following disease characteristics are eligible (specific population subject to FDA Dato-DXd label):
• Patients with unresectable or metastatic HR+/HER2- (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer who have received prior ET and chemotherapy for unresectable or metastatic disease.
• Adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy. Participants will be enrolled upon FDA approval on use of Dato-DXd for this indication.
• Patients with locally advanced or metastatic EGFRm NSCLC who have received prior EGFR-directed therapy and platinum-based chemotherapy.
• Age
• Patient must be ≥ 18 years, at the time of signing the informed consent.
• Type of Patient and Disease Characteristics-
• Has documentation that Dato-DXd will be prescribed for the labelled indication and has not received any dose of Dato-DXd prior to enrollment.
• Is willing to comply with use of prophylactic dexamethasone mouthwash at the start of first infusion and throughout Dato-DXd administration.
• ECOG performance status 0 or 1.
• Has adequate bone marrow function (hemoglobin ≥ 9 g/dL; red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment).
• All women of childbearing potential must have a negative serum pregnancy test result at screening.
• Informed Consent

You may not qualify if:

• Patients are excluded from the study if any of the following criteria apply:
• Has received Dato-DXd prior to enrollment.
• Medical Conditions
• As judged by the investigator, any evidence of cardiac, pulmonary, vascular, and other renal conditions which in the investigator's opinion makes it undesirable for the patient to participate in the study.
• Has any-grade active and uncontrolled stomatitis or mouth ulcers at baseline (participants with prior medical history of stomatitis or mouth ulcers are eligible).
• Use of steroid-containing mouthwash is contraindicated in, including but not limited to:
• Active oral infections (eg, viral, bacterial, or fungal), where the use of a steroid-containing mouthwash may impair local immune response and delay healing
• Known hypersensitivity or allergy to corticosteroids or any excipients contained in the mouthwash formulation
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localized fungal infections of skin or nails are eligible).
• Has clinically significant corneal disease.
• Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients of Dato-DXd (including, but not limited to, polysorbate 80).
• Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
• Is pregnant, or breastfeeding, or planning to become pregnant.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

Sponsors & Collaborators

• AstraZeneca: lead
• Daiichi Sankyo: collaborator

Study Sites (20)

Research Site

Tucson, Arizona, 85719, United States

Location

Research Site

Hot Springs, Arkansas, 71913, United States

Location

Research Site

Little Rock, Arkansas, 72205, United States

Location

Research Site

Duarte, California, 91010, United States

Location

Research Site

Glendale, California, 91204, United States

Location

Research Site

Lakewood, California, 90805, United States

Location

Research Site

Torrance, California, 90505, United States

Location

Research Site

Athens, Georgia, 30607, United States

Location

Research Site

Park Ridge, Illinois, 60068, United States

Location

Research Site

Fort Wayne, Indiana, 46825, United States

Location

Research Site

Lexington, Kentucky, 40503, United States

Location

Research Site

Louisville, Kentucky, 40207, United States

Location

Research Site

Detroit, Michigan, 48202, United States

Location

Research Site

Reno, Nevada, 89502, United States

Location

Research Site

Westbury, New York, 11590, United States

Location

Research Site

Greensboro, North Carolina, 27403, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

Location

Research Site

Knoxville, Tennessee, 37920, United States

Location

Research Site

Fairfax, Virginia, 22031, United States

Location

Research Site

Milwaukee, Wisconsin, 64111, United States

Location

MeSH Terms

Conditions

Stomatitis

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2026
• First Posted: January 22, 2026
• Study Start: February 27, 2026
• Primary Completion (Estimated): October 9, 2027
• Study Completion (Estimated): October 9, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved, AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (20)