A Clinical Study of Patritumab Deruxtecan to Treat Breast Cancer (MK-1022-016)
- Conditions
- Breast Neoplasms
- Interventions
- Registration Number
- NCT07060807
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1000
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 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
-
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 (ART)
-
An ECOG performance status of 0 or 1 assessed within 7 days before randomization
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 (mBC)
-
Has received prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) 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
- Note: 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-CNS disease, or required corticosteroids for radiation-related toxicities, within 14 days of the first dose of study intervention
-
Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
-
Known additional malignancy that is progressing or has required active treatment within the past 3 years
-
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
-
Severe hypersensitivity (≥Grade 3) to HER3-DXd and/or any of its excipients
-
Severe hypersensitivity (≥Grade 3) to all the available TPC and/or any of their excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Patritumab Deruxtecan Patritumab deruxtecan Participants receive patritumab deruxtecan via intravenous (IV) infusion every 3 weeks (Q3W) for approximately 13 months. Treatment of Physician's Choice Paclitaxel 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 of Physician's Choice Nab-paclitaxel 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 of Physician's Choice Capecitabine 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 of Physician's Choice Liposomal doxorubicin 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 of Physician's Choice Trastuzumab deruxtecan 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.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Up to approximately 45 months PFS is defined as the time from first day of study intervention to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by blinded independent central review (BICR). Per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.
Overall Survival (OS) Up to approximately 85 months OS is the length of time from when the participant starts treatment until death from any cause.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to approximately 85 months ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR.
Duration of Response (DOR) Up to approximately 85 months For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score Baseline and up to approximately 85 months The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score (the standardized average of the raw scores) will be presented.
Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score Baseline and up to approximately 85 months The EORTC QLQ-C30 is a cancer specific health-related quality-of-life questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate better physical functioning. The change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) combined score (the standardized average of the raw scores) will be presented.
Change from Baseline in the EORTC-QLQ-C30 Emotional Functioning (Items 1-5) Combined Score Baseline and up to approximately 85 months The EORTC QLQ-C30 is a cancer specific health-related quality-of-life questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate better emotional functioning. The change from baseline in EORTC QLQ-C30 Emotional Functioning (Items 21-24) combined score (the standardized average of the raw scores) will be presented.
Change from Baseline in the EORTC-QLQ-C30 Pain (Items 9 and 19) Combined Score Baseline and up to approximately 85 months The EORTC QLQ-C30 is a cancer specific health-related quality-of-life questionnaire. Participant responses to 2 questions about their pain (Items 9 and 19) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate greater pain. The change from baseline in EORTC QLQ-C30 Pain (Items 9 and 19) combined score (the standardized average of the raw scores) will be presented.
Time to First Deterioration (TTD) in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score Baseline and up to approximately 85 months The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome. The TTD from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score (the standardized average of the raw scores), defined as the time from baseline to the first onset of a 10 or more points deterioration from baseline, will be presented.
TTD in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score Baseline and up to approximately 85 months The EORTC QLQ-C30 is a cancer specific health-related quality-of-life questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate better physical functioning. The TTD from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) combined score (the standardized average of the raw scores), defined as the time from baseline to the first onset of a 10 or more points deterioration from baseline, will be presented.
TTD in the EORTC-QLQ-C30 Emotional Functioning (Items 1-5) Combined Score Baseline and up to approximately 85 months The EORTC QLQ-C30 is a cancer specific health-related quality-of-life questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate better emotional functioning. The TTD from baseline in EORTC QLQ-C30 Emotional Functioning (Items 21-24) combined score (the standardized average of the raw scores) defined as the time from baseline to the first onset of a 10 or more points deterioration from baseline, will be presented.
TTD in the EORTC-QLQ-C30 Pain (Items 9 and 19) Combined Score Baseline and up to approximately 85 months The EORTC QLQ-C30 is a cancer specific health-related quality-of-life questionnaire. Participant responses to 2 questions about their pain (Items 9 and 19) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate greater pain. The TTD from baseline in EORTC QLQ-C30 Pain (Items 9 and 19) combined score (the standardized average of the raw scores), will be presented.
Number of Participants Who Experience One or More Adverse Event (AEs) Up to approximately 85 months An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be presented.
Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 85 months An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be presented.