Study of Patritumab Deruxtecan With Other Anticancer Agents in Participants With HER2 Positive Breast Cancer That Has Spread and Cannot Be Surgically Removed (MK-1022-009)
- Conditions
- Interventions
- Registration Number
- NCT06686394
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Researchers want to learn if patritumab deruxtecan (MK-1022) can treat certain breast cancers. The breast cancers being studied are HER2 positive unresectable locally advanced or metastatic (the cancer has spread to other parts of the body). The goals of this study are to learn:
* About the safety and how well people tolerate of patritumab deruxtecan
...
- Detailed Description
The following countries will be participating in the trial: Canada, United Kingdom, Israel, Japan, South Korea, and USA.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 81
The main inclusion criteria include but are not limited to the following:
- Has histologically confirmed HER2+ locally advanced unresectable breast cancer or metastatic breast cancer
- Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable hepatitis B virus (HBV) viral load before allocation
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 7 days before start of study intervention
Arm 1:
- Has received at least a minimum of 2 and a maximum of 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting
- Had disease progression on or after any previous trastuzumab deruxtecan (T-DXd) treatment
Arm 2:
-Has received no more than 5 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting
Arm 3:
- Has received and had disease progression from T-DXd treatment in any setting and a maximum of 3 prior lines of anti-HER2 therapy in the locally advanced or metastatic setting. T-DXd must be the most recent therapy received before enrollment.
- Has not received tucatinib, lapatinib, or neratinib, or any investigational HER2-targeted tyrosine kinase inhibitors in the locally advanced or metastatic setting
The main exclusion criteria include but are not limited to the following:
- Uncontrolled or significant cardiovascular disease
- History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/interstitial lung disease
- Has clinically severe respiratory compromise
- Has any history of or evidence of any current leptomeningeal disease
- Has clinically significant corneal disease
- Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection
- HIV infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Known additional malignancy that is progressing or has required active treatment within the past 3 years
- Evidence of spinal cord compression or brain metastases
- Has an active infection requiring systemic therapy
- Concurrent active HBV and HCV infection
- Has had major surgical procedure (excluding placement of vascular access) less than 28 days
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Patritumab deruxtecan plus trastuzumab Patritumab deruxtecan Participants receive patritumab deruxtecan intravenous (IV) infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus trastuzumab Trastuzumab Participants receive patritumab deruxtecan intravenous (IV) infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus trastuzumab Trastuzumab Biosimilar Participants receive patritumab deruxtecan intravenous (IV) infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus pertuzumab and trastuzumab Patritumab deruxtecan Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus pertuzumab and trastuzumab Trastuzumab Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus pertuzumab and trastuzumab Trastuzumab Biosimilar Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus pertuzumab and trastuzumab Pertuzumab Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus trastuzumab and tucatinib Patritumab deruxtecan Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus trastuzumab and tucatinib Trastuzumab Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus trastuzumab and tucatinib Trastuzumab Biosimilar Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision. Patritumab deruxtecan plus trastuzumab and tucatinib Tucatinib Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision.
- Primary Outcome Measures
Name Time Method Number of Participants Experiencing Dose-Limiting Toxicity (DLT) Up to 21 days DLT will be defined as any drug-related AE observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. The number of participants who experience a DLT will be presented.
Number of Participants with One or More Adverse Events (AEs) Up to approximately 14 months An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be presented.
Number of Participants who Discontinue Study Intervention Due to an AE Up to approximately 12 months An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
- Secondary Outcome Measures
Name Time Method Maximum Plasma Concentration (Cmax) of Patritumab Deruxtecan Antibody-Drug Conjugate (ADC) At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the Cmax of patritumab deruxtecan ADC.
Trough Concentration (Ctrough) of Patritumab Deruxtecan ADC At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the Ctrough of patritumab deruxtecan ADC.
Area Under the Plasma Concentration-Time Curve (AUC) of Patritumab Deruxtecan ADC At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the AUC of patritumab deruxtecan ADC.
Maximum Plasma Concentration (Cmax) of Total Patritumab Deruxtecan Antidrug Antibody (ADA) At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the Cmax of total patritumab deruxtecan ADA.
Trough Concentration (Ctrough) of Total Patritumab Deruxtecan ADA At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the Ctrough of total patritumab deruxtecan ADA.
Area Under the Plasma Concentration-Time Curve (AUC) of Total Patritumab Deruxtecan ADA At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the AUC of total patritumab deruxtecan ADA.
Maximum Plasma Concentration (Cmax) of Patritumab Deruxtecan Free Payload At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the Cmax of patritumab deruxtecan free payload.
Trough Concentration (Ctrough) of Patritumab Deruxtecan Free Payload At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the Ctrough of patritumab deruxtecan free payload.
Area Under the Plasma Concentration-Time Curve (AUC) of Patritumab Deruxtecan Free Payload At designated time points (up to ~24 months) Blood samples collected at designated time points will be used to determine the AUC of patritumab deruxtecan free payload.