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. (TROPION-SWISH)

AstraZeneca

Status and phase: Begins enrollment this month; Phase 4

Conditions: Stomatitis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT07357597

D926UL00001

Details and patient eligibility

About

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.

Full description

The purpose of this Phase IV study is to describe the incidence and severity of Dato-DXd treatment-emergent grade ≥ 2 stomatitis in participants receiving prophylactic dexamethasone mouthwash within the first 12 weeks of study treatment (ie, Dato-DXd dosing).

The study will enroll an estimated 100 participants across approximately 35 sites in the U.S. Enrollment of participants is planned to occur over approximately 18 months, with a minimum of 12 weeks of follow-up for each participant after the first Dato-DXd dose.

This study has one arm, and the study population will consist of 2 independent cohorts (approximately 50 participants in each cohort):

• Breast cohort (Cohort 1)
• Lung cohort (Cohort 2)

Participants will receive the study intervention, dexamethasone mouthwash, throughout the duration of their standard of care treatment with Dato-DXd.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients are eligible to be included in the study only if all the following criteria apply:

Disease Characteristics

1. 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.

   OR

   • 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.

   OR

   • Patients with locally advanced or metastatic EGFRm NSCLC who have received prior EGFR-directed therapy and platinum-based chemotherapy.

   Age

2. Patient must be ≥ 18 years, at the time of signing the informed consent.

   Type of Patient and Disease Characteristics-

3. Has documentation that Dato-DXd will be prescribed for the labelled indication and has not received any dose of Dato-DXd prior to enrollment.

4. Is willing to comply with use of prophylactic dexamethasone mouthwash at the start of first infusion and throughout Dato-DXd administration.

5. ECOG performance status 0 or 1.

6. Has adequate bone marrow function (hemoglobin ≥ 9 g/dL; red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment).

7. All women of childbearing potential must have a negative serum pregnancy test result at screening.

   Informed Consent

8. Capable of giving signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the ICF and the protocol.

Exclusion criteria

Patients are excluded from the study if any of the following criteria apply:

1. Has received Dato-DXd prior to enrollment.

   Medical Conditions

2. 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.

3. Has any-grade active and uncontrolled stomatitis or mouth ulcers at baseline (participants with prior medical history of stomatitis or mouth ulcers are eligible).

4. 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

5. 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).

6. Has clinically significant corneal disease.

7. Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients of Dato-DXd (including, but not limited to, polysorbate 80).

8. Has a history of severe hypersensitivity reactions to other monoclonal antibodies.

9. Is pregnant, or breastfeeding, or planning to become pregnant.

   Other Exclusions

10. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

11. 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.

12. Previous enrollment in the present study.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

100 participants in 1 patient group

Dexamethasone 0.5 mg/5 mL Mouthwash

Experimental group

Description:

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

Treatment:

Drug: Datopotamab Deruxtecan (Dato-DXd)

Drug: Dexamethasone mouthwash