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Patritumab deruxtecan for HR+/HER2- unresectable locally advanced or metastatic breast cancer

An Open-label, Randomized, Phase 3 Study to Evaluate Patritumab Deruxtecan Monotherapy Versus Treatment of Physician's Choice in Hormone Receptor-positive, HER2-negative Unresectable Locally Advanced or Metastatic Breast Cancer (HERTHENA-Breast04)

Phase 3 Interventional Merck Sharp & Dohme LLC · NCT07060807

This trial tests whether patritumab deruxtecan helps people with hormone receptor–positive, HER2‑negative advanced breast cancer who have progressed on CDK4/6 inhibitor plus endocrine therapy live longer or have slower cancer growth compared with standard chemotherapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1000 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionschemotherapy, radiation, patritumab, trastuzumab
Locations176 sites (Daphne, Alabama and 175 other locations)
Trial IDNCT07060807 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial compares patritumab deruxtecan (HER3‑DXd) to physician‑choice chemotherapy options (paclitaxel, nab‑paclitaxel, capecitabine, or liposomal doxorubicin) in patients with HR+/HER2‑ unresectable locally advanced or metastatic breast cancer. Eligible participants must have centrally confirmed HR+/HER2‑ status, a HER3‑evaluable biopsy from a recent lesion, and documented progression on prior CDK4/6 inhibitor plus endocrine therapy. Participants receive the assigned treatment and are followed for overall survival and progression‑free survival, along with safety and tolerability monitoring. The study is sponsored by Merck Sharp & Dohme with collaboration from Daiichi Sankyo and is enrolling at multiple U.S. cancer centers.

Who should consider this trial

Good fit: Adults with HR+/HER2‑ unresectable locally advanced or metastatic breast cancer who progressed on a CDK4/6 inhibitor plus endocrine therapy, have centrally confirmed marker status, and can provide a HER3‑evaluable recent biopsy.

Not a fit: Patients whose tumors are HER2‑positive, who have not received prior CDK4/6 inhibitor plus endocrine therapy, who cannot provide the required biopsy, or who have medical conditions preventing study treatments are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this treatment could help patients live longer or delay cancer progression compared with current chemotherapy options.

How similar studies have performed: Early‑phase studies of HER3‑targeting antibody–drug conjugates, including patritumab deruxtecan, have shown promising activity in some breast cancer patients, but definitive phase 3 evidence is not yet established.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has a diagnosis of hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)- invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent
* Has centrally-confirmed HR+ and HER2- results and human epidermal growth factor receptor 3 (HER3) evaluable results from a biopsy obtained from a distant metastatic site or a locally advanced lesion on or after the most recent line of therapy (with certain exceptions)
* Must have had progression or recurrence on prior cyclin-dependent kinase (CDK)4/6 inhibitor + endocrine therapy (ET) with one of the following:

  * Radiographic disease progression, as assessed by the investigator, on CDK4/6 inhibitor + ET as 1L for treatment of unresectable locally advanced or metastatic HR+/HER2- breast cancer. CDK4/6 inhibitor + ET must be the only line of therapy received in the advanced setting, or
  * Disease recurrence, either radiographic and/or confirmed histologically via biopsy as assessed by the investigator, while on adjuvant ET in combination with a CDK4/6 inhibitor OR within 24 months from the date of last dose of adjuvant CDK4/6 inhibitor
* Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
* Has an Eastern Cooperative Oncology Group performance status of 0 or 1 assessed within 7 days before randomization

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has breast cancer amenable to treatment with curative intent
* Is eligible to receive additional endocrine-based treatment in the advanced setting as determined by the investigator
* Has a known germline breast cancer gene (BRCA) mutation (deleterious or suspected deleterious) where poly (ADP-ribose) polymerase (PARP) inhibitor(s) is a potential treatment option
* Has current visceral crisis or is at risk for impending visceral crisis that has or may cause imminent organ compromise and/or other life-threatening complications
* Has any of the following: a pulse oximeter reading \<92% at rest, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has ≥Grade 2 peripheral neuropathy.
* Has clinically significant corneal disease
* Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer
* Has received prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate that consists of a topoisomerase I inhibitor (eg, T-DXd) or any other topoisomerase I inhibitor therapy
* Has received prior systemic anticancer therapy within 4 weeks (or 5 half-lives, whichever is shorter) before randomization; participants previously treated with ET plus a CDK4/6 inhibitor may participate as long as at least 2 weeks have elapsed since the last dose of therapy was administered
* Has received prior radiotherapy for non-central nervous system disease, or required corticosteroids for radiation-related toxicities, within 14 days of the first dose of study intervention
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/interstitial lung disease, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening
* Has severe hypersensitivity (≥Grade 3) to HER3-DXd and/or any of its excipients
* Has severe hypersensitivity (≥Grade 3) to all the available TPC and/or any of their excipients

Where this trial is running

Daphne, Alabama and 175 other locations

+126 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Breast Neoplasms
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.