C50 Cancer de mama
Conditions
Interventions
MK-1022, HER3-DXd (Patritumab deruxtecan): Injection, powder, lyophilized, for solution, 100 mg will be administered, at a dose of 5.6 mg/kg, by intravenous infusion, on days 1, 22, 43, and 64 of each
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 14. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Note: Participants must have completed curative antiviral therapy at least 4 weeks prior to randomization. Hepatitis C screening tests are not required unless: • Known history of HCV infection • As mandated by local guidelines 15. An ECOG performance status of 0 or 1 assessed within 7 days before randomization. 16. Adequate organ function as defined in the following table (Table 5). Specimens must be collected within 7 days before the randomization date. Type of Participant and Disease Characteristics 1. Has a diagnosis of HR+/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. defined as: • ER+ and/or PgR+ on a tumor biopsy obtained from a distant metastasis site before study entry based on most recent ASCO/CAP guidelines. Tumor will be considered HR+ if the tumor shows =1% expression of ER and/or PgR. • HER2- on a tumor biopsy obtained from a distant metastasis site before study entry based on most recent ASCO/CAP guidelines. Tumor will be considered HER2- if the tumor shows HER2 IHC 0, 1+ or IHC 2+/ISH-. 2. Has centrally-confirmed HR+ and HER2- results and HER3 evaluable results from a biopsy obtained from a distant metastatic site on or after the most recent line of therapy. Note 1: ER, PgR, HER2 and HER3 with central results that are unknown or unevaluable will not be considered as valid results for eligibility/stratification. Alternate/additional tumor specimen(s), if available, may be requested for central confirmation if initial tumor tissue is centrally determined to be inadequate for biomarker testing. Note 2: If a sample from a distant (metastatic) site is not available and biopsy of a new metastatic lesion is not feasible due to anatomic site inaccessibility and/or participant safety concerns, an archival tumor tissue sample from the primary site may be accepted after consultation with the Sponsor with documented SCF. The exception is if T-DXd is selected as the TPC option, in which case, tissue from the primary site for central testing will not be permitted. Note 3: For participants who have metastatic disease with coexisting locally advanced lesions, if a newly obtained biopsy from a distant (metastatic) lesion is not feasible due to anatomic site inaccessibility and/or participant safety concerns, a new biopsy from the local recurrence site (breast, chest wall, and/ or regional lymph nodes) is permitted. Note 4: Samples from bone metastases will be acceptable only if there is a soft-tissue component of the tumor and biopsy is taken from the soft-tissue component only. 3. Participants must have had progression or recurrence on prior CDK4/6 inhibitor + ET with one of the following (a or b): a. 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. Note 1: Patients who received a 2L of endocrine-based therapy in the metastatic setting are not eligible. Note 2: Patients who have received only single-agent CDK4/6 inhibitors are not eligible. CDK4/6 inhibitor must have been given in combination with eET to be considered a line of therapy. Patients who have
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Has breast cancer amenable to treatment with curative intent. 2. Is eligible to receive additional endocrine-based treatment in the advanced setting as determined by the investigator. Note: Patients with alterations/mutations in PI3KCA, PTEN, AKT, or ESR1 who are deemed suitable for 2L treatment with ET in combination with targeted therapy, where available, are not eligible. 3. Has a known germline BRCA mutation (deleterious or suspected deleterious) where PARP inhibitor(s) is a potential treatment option (ie, available and not medically contraindicated). 25. Has an ongoing symptomatic SARS-CoV-2 infection except for participants who have recovered clinically but continue to have a detectable presence of SAR-CoV-2 antigen. No COVID-19 testing is required unless mandated by local authorities. Other Exclusions 26. Severe hypersensitivity (=Grade 3) to HER3-DXd and/or any of its excipients. 4. 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. Note: Visceral crisis is defined by severe organ dysfunction, as assessed by signs and symptoms, laboratory studies and rapid progression of disease. a. Liver visceral crisis is defined by rapidly increasing bilirubin >1.5x ULN in the absence of Gilbert’s Syndrome or biliary tract obstruction and is ineligible. b. Lung visceral crisis is defined by rapidly increasing dyspnea at rest, not alleviated by drainage of pleural effusion and is ineligible. 5. Has any of the following: • A pulse oximeter reading 450 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention. 8. Has =Grade 2 peripheral neuropathy. 9. Has clinically significant corneal disease. Prior/Concomitant Therapy 10. Has received prior chemotherapy for unresectable locally advanced or mBC. 11. Has received prior treatment with an anti-HER3 antibody and/or ADC that consists of a topoisomerase I inhibitor (eg, T-DXd) or any other topoisomerase I inhibitor therapy. 12. 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. 13. 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. 14. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Refer to Section 6.5 for information on COVID-19 vaccines. Prior/Concurrent Clinical Study Experience 15. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. Diagnostic Assessments 16. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceedin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measuring elapsed time. Testing: stratified logrank test. Estimation: Stratified Cox model with Efron’s tie handling method. NAME OF THE RESULT: Progression-free survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first.;Measuring elapsed time. Testing: stratified logrank test. Estimation: Stratified Cox model with Efron’s tie handling method. NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The time from randomization to death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Measuring elapsed time. Testing: stratified logrank test. Estimation: Stratified Cox model with Efron’s tie handling method. NAME OF THE RESULT: Progression-free survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first.;Measuring elapsed time. Testing: stratified logrank test. Estimation: Stratified Cox model with Efron’s tie handling method. NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The time from randomization to death due to any cause.;Confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR. NAME OF THE RESULT: Objective Response (OR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout the study;Measuring elapsed time NAME OF THE RESULT: Duration of Response (DOR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The time from the first documented evidence of CR or PR per RECIST 1.1 as assessed by BICR until disease progression or death due to any cause, whichever occurs first.;EORTC QLQ-C30 scores NAME OF THE RESULT: Changes in overall health/quality of life, physical functioning, emotional functioning, and pain. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Change from baseline in EORTC QLQ-C30 global health status/quality of life scores, physical functioning score, emotional functioning score, and pain score.;Measuring elapsed time NAME OF THE RESULT: Time to first deterioration (TTD) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: EORTC QLQ-C30 global health status/quality of life score | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Colombia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea South, Mexico, Peru, Poland, Spain, Taiwan, Thailand, Turkey, United Kindgdom, United States, Vietnam
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed