A Clinical Study of Patritumab Deruxtecan to Treat Breast Cancer (MK-1022-016)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3

Conditions: Breast Neoplasms

Treatments: Drug: Paclitaxel; Biological: Patritumab deruxtecan; Drug: Nab-paclitaxel; Biological: Trastuzumab deruxtecan; Drug: Liposomal doxorubicin; Drug: Capecitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT07060807

jRCT2031250297 (Registry Identifier)

1022-016

U1111-1317-5490 (Registry Identifier)

2025-520582-51-00 (Registry Identifier)

Details and patient eligibility

About

Researchers are looking for other ways to treat breast cancer (BC) that is hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) and either unresectable locally advanced or metastatic.

• HR positive (HR+) means the cancer cells have proteins that attach to estrogen or progesterone (hormones) which help the cancer to grow and spread
• HER2 negative (HER2-) means the cancer cells have a low amount of a protein called HER2
• Unresectable locally advanced means the cancer cannot be completely removed by surgery and has spread into nearby tissue or muscles
• Metastatic means the cancer has spread to other parts of the body

Treatment for this type of breast cancer usually includes endocrine therapy (ET) and sometimes a second treatment. The main goal of this study is to learn if people who receive patritumab deruxtecan (also known as HER3-DXd and MK-1022) live longer overall or without the cancer growing/spreading, compared to people who receive chemotherapy or a different drug called trastuzumab deruxtecan.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,000 participants in 2 patient groups

Patritumab Deruxtecan

Experimental group

Description:

Participants receive patritumab deruxtecan via intravenous (IV) infusion every 3 weeks (Q3W) for approximately 13 months.

Treatment:

Biological: Patritumab deruxtecan

Treatment of Physician's Choice

Active Comparator group

Description:

Participants receive treatment of physician's choice (TPC) for up to 13 months. The TPC may be any of the following options: Paclitaxel (80 mg/m\^2) on Days 1, 8, 15, and 22 of each 4-week cycle; Paclitaxel (90 mg/m\^2) on Days 1, 8, and 15 of each 4-week cycle; Nab-paclitaxel (100 mg/m\^2) on Days 1, 8, and 15 of each 4-week cycle; Capecitabine (1000 mg/m\^2) bid on Days 1 to 14 of each 3-week cycle; Liposomal doxorubicin (50 mg/m\^2) on Day 1 of each 4-week cycle; or trastuzumab deruxtecan (T-DXd) (5.4 mg/kg) Q3W.

Treatment:

Drug: Liposomal doxorubicin

Drug: Capecitabine

Biological: Trastuzumab deruxtecan

Drug: Nab-paclitaxel

Drug: Paclitaxel