NCT05865990: TUXEDO-3

Multicenter, Single-arm, 3 Cohort, Phase II Trial of HER3-DXd in Patients With Active Brain Metastases From Metastatic Breast Cancer and Non-small Cell Lung Cancer, and in Patients With Leptomeningeal Disease From Advanced Solid Tumors

Completed Phase 2 Last updated 28 April 2026

What this trial tests

Phase 2 trial testing Patritumab deruxtecan in Metastatic Breast Cancer in 63 participants. Completed in 3 April 2026.

Timeline

24 November 2023

Primary endpoint
29 November 2024

3 April 2026

Quick facts

Lead sponsor	MedSIR
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	63
Start date	24 November 2023
Primary completion	29 November 2024
Estimated completion	3 April 2026
Sites	8 locations across Austria, Spain

Drugs / interventions tested

• Patritumab deruxtecan — full drug profile →

Conditions studied

• Metastatic Breast Cancer — all drugs for Metastatic Breast Cancer →
• Advanced Non-Small Cell Squamous Lung Cancer — all drugs for Advanced Non-Small Cell Squamous Lung Cancer →
• Solid Tumor, Adult — all drugs for Solid Tumor, Adult →

Sponsor

MedSIR — full company profile →

Who can join

18 and older, any sex, with Metastatic Breast Cancer or Advanced Non-Small Cell Squamous Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Efficacy: Local determination of intracranial objective response rate (ORR-IC) in cohort 1 and cohort 2.
  Time frame: From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months
  Rate of patients with complete response (CR) or partial response (PR) determined locally by investigator, using Response Assessment in Neuro-Oncology Brain Metastases (RANO)-BM criteria in cohort 1 and cohort 2.
• Efficacy: Overall survival (OS) rate at 3 months in cohort 3.
  Time frame: From baseline up to 3 months
  3-month OS, defined as the rate of patients alive at 3 months after treatment initiation in cohort 3.

Sponsor's own description

The goal of this phase II clinical trial\] is to analyze the efficacy of patritumab deruxtecan (HER3-DXd) in patients with metastatic breast cancer (MBC) or advanced non-small cell lung cancer (aNSCLC) with active brain metastases (BM) who have received at least one line of systemic therapy in the advanced setting, or patients with active leptomeningeal carcinomatosis/disease (LMD) after radiotherapy from an advanced solid tumor who do not need immediate local treatment, and have not received prior treatment with an anti-HER3 targeted drug\].

The main questions it aims to answer are:

* The intracranial objective response rate (ORR-IC) per local investigator as judged by best central nervous system (CNS) response according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria of HER3-DXd in patients with active BM from MBC (Cohort 1) and aNSCLC (Cohort 2).
* The overall survival (OS) rate at 3 months of HER3-DXd in patients with advanced solid tumors with untreated LMD (Cohort 3).

Participants will receive HER3-DXd on day (D1) of each 21-day cycle until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

Researchers will compare historical groups to see if HER3-DXd positively impacts patient outcomes.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current and future immunotherapy for breast cancer.
   Heater NK, Warrior S, Lu J. · · 2024 · cited 38× · PMID 39722028 · DOI 10.1186/s13045-024-01649-z
2. Toxicities and management strategies of emerging antibody-drug conjugates in breast cancer.
   Kang S, Kim SB. · · 2025 · cited 15× · PMID 40151551 · DOI 10.1177/17588359251324889
3. The clinical development of antibody-drug conjugates for non-small cell lung cancer therapy.
   Liu X, Deng J, Zhang R, Xing J, et al · · 2023 · cited 15× · PMID 38162667 · DOI 10.3389/fimmu.2023.1335252
4. Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer.
   Wen J, Yu JZ, Liu C, Ould Ismail AAO, et al · · 2024 · cited 13× · PMID 38396722 · DOI 10.3390/ijms25042044
5. Antibody drug conjugates in the clinic.
   Udofa E, Sankholkar D, Mitragotri S, Zhao Z. · · 2024 · cited 12× · PMID 39545074 · DOI 10.1002/btm2.10677
6. Targeted therapy of non-small cell lung cancer: mechanisms and clinical trials.
   Yu L, Yang R, Long Z, Tao Q, et al · · 2024 · cited 12× · PMID 39391239 · DOI 10.3389/fonc.2024.1451230
7. Advancements in antibody-drug conjugates as cancer therapeutics.
   Fong JY, Phuna Z, Chong DY, Heryanto CM, et al · · 2025 · cited 11× · PMID 40814440 · DOI 10.1016/j.jncc.2025.01.007
8. Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial.
   Preusser M, Garde-Noguera J, García-Mosquera JJ, Gion M, et al · · 2025 · cited 11× · PMID 40447851 · DOI 10.1038/s41591-025-03744-1