This trial is testing pembrolizumab (pembro) + chemotherapy (chemo) in people with certain types of breast cancer called hormone receptor positive/ human epidermal growth factor receptor 2-negative (HR+/HER2-) locally advanced inoperable or metastatic breast cancer (MBC).

Phase 1

• Conditions: Treatment of patients with HR+/HER2- locally recurrent inoperable or MBC whose tumors express PD-L1; MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005407-38-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-02
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 800

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 2 or more lines of endocrine therapy for metastatic HR+/HER2-disease, with at least 1 given in combination with a CDK4/6 inhibitor. OR Has progressed on 1 line of endocrine therapy for metastatic HR+/HER2- disease and had a relapse within 24 months of definitive surgery for primary tumor while on adjuvant endocrine therapy. Prior treatment with a CDK4/6 inhibitor (in the metastatic and/or adjuvant setting) is required. OR If no prior treatment with a CDK 4/6 inhibitor, participants must have progressed within 6 months of starting 1 line of endocrine therapy for metastatic disease and had a relapse within 24 months of definitive surgery for primary tumor and while on adjuvant endocrine therapy.
3. Has presented a documented progression (confirmed by scans per RECIST 1.1 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 PD based on investigator review of at least 2 scans per RECIST 1.1 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 in the neoadjuvant/adjuvant setting can be treated with same class of chemotherapy (taxane or anthracycline) 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. o Participants who presented with de novo metastatic disease at initial breast cancer diagnosis, are eligible for the study, if they have progressed on 2 or more lines of endocrine therapy for metastatic HR+/HER2- disease, with at least 1 given in combination with a CDK4/6 inhibitor and they present a documented progression during the last administered endocrine therapy prior to entering the study.
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
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 participate if they agree to the following during the study intervention period and for at least 90 days after the last dose of chemotherapy:
• Refrain from donating sperm
• Be abstinent from heterosexual intercourse or must agree to use contraception unless confirmed to be azoospermic

For more Inclusion crit

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.
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-PDL2 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 palliative radiotherapy prior to start of study intervention and has not recovered from all radiation-related toxicities and/or requires corticosteroids, and/or has radiation pneumonitis. At least a 1-week washout is required for palliative radiation. Participants who received prior radiotherapy to >=25% of bone marrow are not eligible regardless of when it was received.
11. Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention.
12. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention

For more Exclusion Criteria see the protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified