Treatment of patients with HR+/HER2- locally recurrent inoperable or MBC whose tumors express PD-L1 MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA ve
Conditions
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has locally recurrent inoperable or metastatic HR+/HER2- breast cancer, which has not been previously treated with cytotoxic chemotherapy in the noncurative setting. 2. Has progressed on prior endocrine therapy and is now a chemotherapy candidate, meeting the characteristics in regard to previous treatments of one of the following 4 groups: GROUP 1: Has progressed on 2 or more lines of endocrine therapy for advanced/metastatic HR+/HER2-disease, with at least 1 given in combination with a CDK4/6 inhibitor. Prior treatment with mTOR and/or PI3-K inhibitors is allowed. OR GROUP 2a: Has progressed on 1 line of previous endocrine therapy for advanced/metastatic disease AND had a disease recurrence within 24 months of definitive surgery for the primary tumor and while on adjuvant endocrine therapy. Prior use of CDK4/6 inhibitors is required, either in the adjuvant and/or metastatic setting. Prior treatment with mTOR and/or PI3-K inhibitors is allowed. OR GROUP 2b: Has progressed within 12 months of starting 1 line of endocrine therapy with a CDK4/6 inhibitor for advanced/metastatic HR+/HER2- disease. OR GROUP 3: If no prior treatment with a CDK4/6 inhibitor for advanced/metastatic disease and/or early stage disease (adjuvant), participants must have progressed within 6 months of starting 1 line of endocrine therapy with or without an mTOR or PI3-K inhibitor for metastatic disease AND had a relapse within 24 months of definitive surgery for primary tumor and while receiving adjuvant endocrine therapy. 3. Has presented a documented radiographic disease progression as assessed by the investigator and/or histology [biopsy or cytology] for participants presenting with new metastatic lesions) during or after the last administered endocrine therapy prior to entering the study. o There is evidence of radiographic disease progression based on investigator review of at least 2 scans following initiation of the last endocrine therapy (or combination) for metastatic disease. o A laboratory report indicating tumor marker elevation cannot be used as documentation of local or distant disease recurrence. 4. Is a chemotherapy candidate that meets the following criteria: o Participants who received taxane and/or anthracyclines (or capecitabine) in the neoadjuvant/adjuvant setting can be treated with same class of chemotherapy (taxane or anthracycline or capecitabine) if =12 months have elapsed between the completion of treatment with curative intent and first documented local or distant disease recurrence. o Participants who will be selected to receive liposomal doxorubicin must have a LVEF of at least 50% or above the institution limit of normal, as assessed by ECHO or MUGA scan performed prior to the first dose administration. 5. Provides a new or the last obtained core biopsy, preferably consisting of multiple cores, taken from a locally recurrent or a distant (metastatic) lesion not previously irradiated for central determination of hormone receptor status (ER and PgR), HER2, and PD-L1 status. 6. Has centrally confirmed PD-L1 CPS =1 and HR+ (ER and/or PgR) /HER2– breast cancer as defined by the most recent ASCO/CAP guidelines on most recent tumor biopsy. 7. Has an ECOG Performance Status of 0 or 1, as assessed within 7 days prior to the first dose of study treatment. 8. Demonstrates adequate organ function, within 10 days prior to the start of study treatment. 9. Participants are at least 18 years of age. 10. Male participants are eligible to parti
Exclusion criteria
Exclusion criteria: 1. Has breast cancer amenable to treatment with curative intent. 2. Has a history or current evidence of any condition, therapy, or laboratory abnormality that is specifically contraindicated per the current locally-approved labeling, that might confound the results of the study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator. 3. Has significant cardiac disease. 4. Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications, such as lymphangitic lung metastases, bone marrow replacement, carcinomatous meningitis, significant symptomatic liver metastases, shortness of breath requiring supplemental oxygen, symptomatic pleural effusion requiring supplemental oxygen, symptomatic pericardial effusion, symptomatic peritoneal carcinomatosis, or the need to achieve rapid symptom control. 5. Has skin only disease. Participants who have metastatic disease fulfilling the previous criteria in addition to skin disease can be enrolled. 6. Has a known germline BRCA mutation and has not received previous treatment with PARP inhibition either in the adjuvant or metastatic setting (where available and not medically contraindicated). Single-agent PARP inhibitor therapy does not count as a line of endocrine therapy. 7. Has received prior chemotherapy for locally recurrent inoperable or metastatic breast cancer. 8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor. 9. Has received prior systemic anticancer therapy with other investigational agents within 4 weeks prior to randomization. 10. Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. 11. Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. 12. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. 13. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. 14. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 15. Has known active CNS metastases. Participants with known brain metastases may participate provided that the brain metastases have been previously treated (except with chemotherapy) and are radiographically stable per local radiology/investigator review. To demonstrate radiographic stability of previously treated brain metastases, a minimum of 2 posttreatment brain scan assessments are required: 1) The first brain scan must be acquired after treatment of brain metastases has been completed; 2) The second brain scan must be obtained during screening and =4 weeks after the previous posttreatment brain scan. 16. Has diagnosed carcinomatous meningitis. 17. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. Or has any hypersensitivity to the planned chemotherapy agent and/or any of their excipients. 18. Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy. 19. Has a history of pneumon
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare pembrolizumab+chemotherapy (CT) to placebo+CT with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR) in participants with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) =10 and =1 tumors, separately. 2. To compare pembrolizumab+CT to placebo+CT with respect to overall survival (OS) in participants with PD-L1 CPS =10 and =1 tumors, separately. ;Secondary Objective: 1. To compare pembrolizumab+CT to placebo+CT with respect to PFS per RECIST 1.1 by investigator in participants with CPS =10 and =1 tumors, separately. 2. To compare pembrolizumab+CT to placebo+CT with respect to objective response rate (ORR) per RECIST 1.1 by BICR in participants with CPS =10 and =1 tumors, separately. 3. To compare pembrolizumab+CT to placebo+CT with respect to disease control rate (DCR) per RECIST 1.1 by BICR in participants with CPS =10 and =1 tumors, separately. 4. To evaluate duration of response (DOR) per RECIST 1.1 by BICR in participants with CPS =10 and =1 tumors, separately. 5. To evaluate health-related quality of life (HRQoL) assessments using European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30) in participants with PD-L1 CPS =10 and =1 tumors, separately . 6. To evaluate safety and tolerability of pembrolizumab+CT. ;Primary end point(s): 1. Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded independent Central Review (BICR) in Participants With CPS =10 2. PFS per RECIST 1.1 by BICR in Participants With CPS =1 3. Overall Survival (OS) in Participants With CPS =10 4. OS in Participants With CPS =1 ;Timepoint(s) of evaluation of this end point: 1. Up to ~33 months 2. Up to ~33 months 3. Up to ~75 months 4. Up to ~75 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS per RECIST 1.1 by Investigator in Participants With CPS =10 2. PFS per RECIST 1.1 by Investigator in Participants With CPS =1 3. Objective Response Rate (ORR) per RECIST 1.1 by BICR in Participants With CPS =10 4. ORR per RECIST 1.1 by BICR in Participants With CPS =1 5. Disease Control Rate (DCR) per RECIST 1.1 by BICR in Participants With CPS =10 6. DCR per RECIST 1.1 by BICR in Participants With CPS =1 7. Duration of Response (DOR) per RECIST 1.1 by BICR in Participants With CPS =10 8. DOR per RECIST 1.1 by BICR in Participants With CPS =1 9. Change From Baseline to end of Study in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS =10 10. Change From Baseline to end of Study in Global Health Status/Quality of Life Score on the EORTC QLQ-C30 in Participants with CPS =1 11. Change From Baseline to end of Study in Physical Functioning Score on the EORTC QLQ-C30 in Participants with CPS =10 12. Change From Baseline to end of Study in Physical Functioning Score on the EORTC QLQ-C30 in Participants with CPS =1 13. Change From Baseline to end of Study in Emotional Functioning Score on the EORTC QLQ-C30 in Participants with CPS =10 14. Change From Baseline to end of Study in Emotional Functioning Score on the EORTC QLQ-C30 in Participants with CPS =1 15. Change From Baseline to end of Study in Fatigue Score on the EORTC QLQ-C30 in Participants with CPS =10 16. Change From Baseline in Fatigue Score on the EORTC QLQ-C30 in Participants with CPS =1 17. Change From Baseline in Diarrhea Score on the EORTC QLQ-C30 in Participants with CPS =10 18. Change From Baseline in Diarrhea Score on the EORTC QLQ-C30 in Participants with CPS =1 19. Time to Deterioration (TTD) in Global Health Status/Quality of Life Score on the EORTC QLQ-C30 in Participants with CPS =10 20. TTD in Global Health Status/Quality of Life Scor | — |
Countries
Argentina, Australia, Austria, Canada, Chile, China, France, Germany, Greece, Guatemala, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Philippines, Poland, Portugal, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States
Outcome results
None listed