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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 time of diagnosis of locally advanced unresectable or metastatic breast cancer. A new biopsy obtained after progression of the most recent line of therapy is preferred
* 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) interstitial lung disease (ILD) or pneumonitis irrespective of steroid use, or has current ILD or suspected ILD, or ILD 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 it's running

• Southern Cancer Center (SCC) ( Site 8000)
  Daphne, Alabama, United States Recruiting
• The University of Arizona Cancer Center - North Campus ( Site 0055)
  Tucson, Arizona, United States Recruiting
• Los Angeles Hematology Oncology Medical Group ( Site 0026)
  Los Angeles, California, United States Recruiting
• Hoag Memorial Hospital Presbyterian ( Site 0025)
  Newport Beach, California, United States Recruiting
• St. Marys Hospital and Regional Medical Center-SCL Health Cancer Centers of Colorado ( Site 0021)
  Grand Junction, Colorado, United States Recruiting
• Medical Oncology Hematology Consultants (MOHC) ( Site 8002)
  Newark, Delaware, United States Recruiting

+156 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Toll Free Number
• Email: Trialsites@msd.com
• Phone: 1-888-577-8839

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• New treatment approach for high-risk early-stage breast cancer

  This study is testing a new combination of treatments for people with high-risk early-stage triple-negative breast cancer to see if it can shrink tumors more than the usual treatment before surgery.

  Recruiting at 17 sites Phase 2 Merck Sharp & Dohme LLC · Santa Monica, California and 16 other locations · NCT06797635

• Treatment of advanced HER2 positive breast cancer with patritumab deruxtecan and other agents

  This study is testing a new treatment combining patritumab deruxtecan with other cancer drugs to see if it helps people with advanced HER2 positive breast cancer that can't be surgically removed.

  Recruiting at 18 sites Phase 1/2 Merck Sharp & Dohme LLC · Aurora, Colorado and 17 other locations · NCT06686394

• Improved Facial Skin Quality After VYC-12L for Breast Cancer Survivors

  This study tests whether intradermal injections of VYC-12L can improve facial skin quality and quality of life in adults who have completed breast cancer treatment.

  Recruiting Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia · Murcia, Murcia · NCT07917117

• Breast cancer subtypes and outcomes in Colombian women

  This study looks back at medical records of women with breast cancer to see how different molecular subtypes relate to survival and recurrence in a single Colombian hospital.

  Recruiting Fundación Santa Fe de Bogota · Bogotá, Bogota D.C. · NCT07856225

• Multimodal psychosomatic symptom care for breast cancer: personalized acupuncture care guided by shared decision-making

  This study tests whether personalized acupuncture options (manual acupuncture, ear acupuncture, or both) can help women with breast cancer who have anxiety, sleep problems, or fatigue, compared to routine nursing care.

  Recruiting at 3 sites First Teaching Hospital of Tianjin University of Traditional Chinese Medicine · Tianjin and 2 other locations · NCT07763587

• Slow Jogging for Breast Cancer Survivors

  This study tests whether a 12-week slow jogging program helps sleep quality in women who have completed breast cancer treatment.

  Recruiting Mackay Memorial Hospital · Taipei, Taipei City · NCT07757763

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.