C50 Cancer de mama
Conditions
Interventions
MK-2870 200mg/vial 4mg/kg will be administered by intravenous infusion, every 2 weeks on days 1, 15, 29, 43, 57 and 71 of each 12-week cycle until a treatment discontinuation criterion is met. Likewis
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Type of Participant and Disease Characteristics 1. Has unresectable locally advanced or metastatic centrally-confirmed HR+/HER2- breast cancer, defined as: • ER+ and/or PgR+ as determined by central testing on a tumor biopsy obtained preferably from a distant metastasis site or a local recurrence before study entry based on ASCO/CAP guidelines. Tumor will be considered HR+ if the tumor shows =1% expression of ER or PgR. • HER2- as determined by central testing on a tumor biopsy obtained preferably from a distant metastasis site or a local recurrence before study entry based on ASCO/CAP guidelines. Tumor will be considered HER2- if the tumor shows HER2 zero or low, defined as IHC 0, 1+ or IHC 2+/ISH-. Note 1: ER/HER2/PD-L1/TROP2 reported as unknown or unevaluable will not be considered as valid result for eligibility/stratification. No TROP2 expression will be considered as “Low”. Note 2: Participants initially diagnosed with HER2+ breast cancer and TNBC are allowed but must have central confirmation of HR+/HER2- breast cancer in the most recent tumor biopsy obtained (last archival or newly obtained from a distant metastasis site or a local recurrence). Note 3: If an archival sample from a locally recurrent or 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. Note 4: 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 disease (breast, chest wall, and/ or regional lymph nodes) is permitted. Note 5: Tumor tissue from bone metastasis (without soft tissue component) is not evaluable for biomarker status and therefore, this is not acceptable. Soft tissue from bone metastasis is acceptable. Note 6: Adequacy of biopsy specimen for the above analyses must be confirmed by the central laboratory. Submission of another tumor specimen may be required if adequate tumor tissue was not provided the first time. Type of Participant and Disease Characteristics 2. Participants must have either: • Radiographic disease progression, as assessed by the investigator, on one or more lines of endocrine therapy for unresectable locally advanced/metastatic HR+/HER2- breast cancer, with one in combination with a CDK4/6 inhibitor. OR • Radiographic disease progression as assessed by the investigator within 6 months (ie, =6 months) of starting 1L endocrine therapy in combination with a CDK4/6 inhibitor that was prematurely discontinued (before experiencing radiologic disease progression due to intolerance) for unresectable locally advanced or metastatic disease. OR • Radiographic disease progression as assessed by the investigator after 6 months (ie, >6 months) of starting 1L endocrine therapy in combination with a CDK 4/6 inhibitor that was prematurely discontinued (before experiencing radiologic disease progression due to intolerance) AND have also experienced radiologic disease progression on an additional endocrine therapy, either as monotherapy or as combination therapy (with a PI3K inhibitor or an mTOR inhibitor), for unresectable locally advanced or metastatic disease. OR • A relapse during, or within 12 mont
Exclusion criteria
Exclusion criteria: Medical conditions 3. Has a known ESR1 mutation and has not received previous treatment with elacestrant (where available and not medically contraindicated). Medical conditions 1. Has breast cancer amenable to treatment with curative intent. Medical conditions 2. Has experienced an early recurrence (1.5 x ULN in the absence of biliary obstruction with involvement of over than 50% of liver parenchyma by the disease. Medical conditions 7. Has skin only disease. Participants who have metastatic disease fulfilling the previous criteria in addition to skin disease can be enrolled. Medical conditions 8. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea). Medical conditions 9. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention. Medical conditions 10. Has Grade =2 peripheral neuropathy. Medical conditions 11. Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing. Prior/Concomitant Therapy 12. Has received prior chemotherapy for unresectable locally advanced or MBC. Prior/Concomitant Therapy 13. Has received prior tr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time from randomization to first documented disease progression by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death from any cause, let it happen first. NAME OF THE RESULT: Efficacy endpoint: Progression-free survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: On-study imaging scans will be performed at 9 weeks (63 days ± 7 days) from the date of randomization. Subsequent tumor imaging scans should be performed every 9 weeks (63 days ± 7 days) or more frequently if clinically indicated. After 54 weeks (378 days ± 7 days), participants remaining on treatment will undergo imaging scans every 12 weeks (84 days ± 7 days) at the time of discontinuation (If an imaging scan was obtained within 4 weeks before discontinuation of treatment, no additional imaging examination will be necessary to EOT) and 30 days after the last dose.;Safety analyzes will be conducted in the APaT population, which consists of all randomized participants who received at least one dose of the study intervention. Review parameters such as: incidence, causality and clinical outcome of AE/SAE. In a summary by treatment group of the number and percentage of participants with at least one AE, one drug-related AE, one serious AE, one serious drug-related AE, one grade 3 to AE 5, a grade 3 to 5 drug-related AE. AEs will be evaluated according to the definition of version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE). The change from the initial value will be evaluated in the analysis. Vital signs and laboratory tests will only be included for participants who have at least one measurement obtained after receiving at least one dose of the study intervention. Estimate of change from baseline in laboratory values ??and vital signs, summary statistics will be provided by treatment group for baseline values, during treatment, and change from baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| Time from randomization to first documented disease progression by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death from any cause, let it happen first. NAME OF THE RESULT: Efficacy endpoint: Progression-free survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: On-study imaging scans will be performed at 9 weeks (63 days ± 7 days) from the date of randomization. Subsequent tumor imaging scans should be performed every 9 weeks (63 days ± 7 days) or more frequently if clinically indicated. After 54 weeks (378 days ± 7 days), participants remaining on treatment will undergo imaging scans every 12 weeks (84 days ± 7 days) at the time of discontinuation (If an imaging scan was obtained within 4 weeks before discontinuation of treatment, no additional imaging examination will be necessary to EOT) and 30 days after the last dose.;Safety analyzes will be conducted in the APaT population, which consists of all randomized participants who received at least one dose of the study intervention. Review parameters such as: incidence, causality and clinical outcome of AE/SAE. In a summary by treatment group of the number and percentage of participants with at least one AE, one drug-related AE, one serious AE, one serious drug-related AE, one grade 3 to AE 5, a grade 3 to 5 drug-related AE. AEs will be evaluated according to the definition of version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE). The change from the initial value will be evaluated in the analysis. Vital signs and laboratory tests will only be included for participants who have at least one measurement obtained after receiving at least one dose of the study intervention. Estimate of change from baseline in laboratory values ??and vital signs, summary statistics will be provided by treatment group for baseline values, during treatment, and change from baseline. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Costa Rica, Czech Republic, Denmark, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Korea South, Malasya, Mexico, Nederland, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kindgdom, United States
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed