Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (TNBC) MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have locally recurrent inoperable centrally confirmed TNBC that has not previously been treated with chemotherapy in the metastatic setting and that cannot be treated with curative intent OR Have metastatic TNBC that has not been previously treated with chemotherapy 2. Have been treated with anthracycline and/or a taxane in the neoadjuvant/adjuvant setting, if they received systemic treatment in the neoadjuvant/adjuvant setting, unless anthracycline and/or taxane was contraindicated or not considered the best treatment option for the participant in the opinion of the treating physician 3. Have measurable disease based on RECIST 1.1, as determined by local radiology review 4. Have provided a recently obtained or archival (no more than 3 years old) core or excisional biopsy of a tumor lesion not previously irradiated for central determination of TNBC, PD-L1, BRCA, and HRD status 5. Be a male or female at least 18 years of age on the day of signing the informed consent 6. Have an ECOG performance status of 0 or 1 as assessed within 7 days prior to the start of induction study treatment 7. Have a life expectancy =27 weeks from the day of first study treatment 8. Demonstrate adequate organ function 9. Must adhere to the following contraceptive use if a male participant: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Male participants are eligible to participate if they agree to the following during the intervention period and for at least 180 days after the last dose of study intervention: •Refrain from donating sperm PLUS either: •Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR •Must agree to use contraception unless confirmed to be azoospermic as detailed below: ? Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant 10. Must adhere to the following contraceptive use if a female participant: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies •A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: •Is not a woman of childbearing potential (WOCBP) OR •Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention
Exclusion criteria
Exclusion criteria: INDUCTION PERIOD 1. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years 2. 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 drug 3. Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment and is allowed 4. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable 5. Has myelodysplastic syndrome/acute myeloid leukemia or has features suggestive of MDS/AML 6. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis 7. Has active, or a history of, interstitial lung disease 8. Has a known history of active tuberculosis 9. Has an active infection requiring systemic therapy 10. Has a known history of HIV infection 11. Has a known history of Hepatitis B or known active Hepatitis C virus infection 12. Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of first study treatment 13. Has neuropathy =Grade 2 14. Has not recovered from AEs due to a previously administered therapy 15. Has a known history of hypersensitivity or allergy to pembrolizumab, olaparib and any of its components, and/or to any of the study chemotherapies and any of their components 16. Has severe hypersensitivity to the study treatments and/or any of their excipients 17. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study 18. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 180 days after the last dose of study treatment 19. Is a WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation 20. Has received prior therapy with either olaparib or any other PARP inhibitor 21. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis 22. Has received colony-stimulating factors within 2 weeks prior to the first dose of study treatment 23. Has had an allogenic tissue/solid organ transplant 24. Has received previous allogenic bone marrow transplant or double umbilical cord transplantation 25. Had major surgery within 2 weeks of starting study intervention or has not recovered from any effects of any major surgery 26. Has received a live vaccine within 30 days prior to first study treatment 27. Is receiving any medication prohibited in combination with study chemotherapies as described in the respective product labels unless medication was stopped within 7 days p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare olaparib plus pembrolizumab to chemotherapy plus pembrolizumab with regards to progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). 2. To compare olaparib plus pembrolizumab to chemotherapy plus pembrolizumab with regards to overall survival (OS). ; Secondary Objective: 1. To evaluate OS, and PFS according to RECIST 1.1 by BICR, in participants with BRCAm tumors following treatment with olaparib plus pembrolizumab or chemotherapy plus pembrolizumab. 2.To evaluate health-related quality-of-life (HRQoL) and time to deterioration (TTD) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the breast cancer module (EORTC QLQBR23) in participants with BRCAm tumors and irrespective of BRCAm status following treatment with olaparib plus pembrolizumab or chemotherapy plus pembrolizumab. 3. To evaluate visual analogue scale (VAS) using the European Quality of Life 5-dimension, 5-level questionnaire (EuroQoL EQ-5D-5L) in participants with BRCAm tumors and irrespective of BRCAm status following treatment with olaparib plus pembrolizumab or chemotherapy plus pembrolizumab. 4.To evaluate the safety and tolerability of olaparib plus pembrolizumab or chemotherapy plus pembrolizumab. ; Primary end point(s): 1. Progression free survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) 2. Overall Survival (OS) ; Timepoint(s) of evaluation of this end point: 1. Up to approximately 60 months 2. Up to approximately 60 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall Survival (OS) in Participants with Breast Cancer Susceptibility Gene Mutation (BRCAm) Tumors 2. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants with Breast Cancer Susceptibility Gene Mutation (BRCAm) Tumors 3. Change From Baseline in Health-Related Quality-of-Life (HRQoL) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 29 and 30 Score 4. Change From Baseline in Physical Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1- 5 Score 5. Change From Baseline in Emotional Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 21-24 Score 6. Change From Baseline in Systemic Therapy Side Effects Using the European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality-of-Life (QoL) Questionnaire (EORTC QLQ-BR23) Items 1-4,6,7, and 8 Score 7. Time to Deterioration in Health-Related Quality-of-Life (HRQoL) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 29 and 30 Score 8. Time to Deterioration in Physical Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1- 5 Score 9. Time to Deterioration in Emotional Functioning Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 21-24 Score 10. Time to Deterioration in Systemic Therapy Side Effects Using the Euro | — |
Countries
Canada, Chile, Colombia, France, Germany, Hungary, Ireland, Japan, Korea, Republic of, Poland, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed