Study of Pembrolizumab (MK-3475) Monotherapy for Metastatic Triple-Negative Breast Cancer (MK-3475-086/KEYNOTE-086)

NCT02447003 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 3475-0862015-000294-13152987
• Study Type: interventional
• Target: 254
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a two-part study of pembrolizumab monotherapy in participants with metastatic triple-negative breast cancer (mTNBC). Part 1 of the study will examine the efficacy and safety of pembrolizumab monotherapy as first line or above treatment in participants who have received either no prior systemic treatment or at least one prior systemic treatment for metastatic breast cancer. Part 2 of the study, if done, will expand the investigation of pembrolizumab treatment in a subgroup of participants from Part 1 and will only start after enrollment in Part 1 has been completed. There will be no hypothesis testing in this study.

Conditions

Breast Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (4)

• Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Central Imaging Vendor (CIV) in All Cohort A Participants

  ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in sum of diameters \[SOD\] of target lesions) per RECIST 1.1 by CIV. ORR was estimated by Agresti-Coull (A-C) method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, for all participants in Cohort A. Per protocol final ORR analysis in all Cohort A participants was done at the time of final statistical efficacy analysis, with a 10-November (Nov)-2017 cutoff. Per protocol ORR per RECIST 1.1 by CIV in all Cohort A participants was planned and conducted as a pre-specified primary outcome analysis. Per protocol ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record.

  Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

• ORR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With Programmed Cell Death- Ligand 1 (PD-L1) Positive Tumor Expression

  ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for the subgroup of Cohort A participants with tumor immunohistochemistry (IHC) defined-PD-L1 positive expression (PD-L1+). Per protocol final ORR analysis in the Cohort A PD-L1+ subgroup was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff. Per protocol all Cohort B participants were PD-L1+ and ORR per RECIST 1.1 by CIV in all Cohort B participants was analyzed separately as a pre-specified secondary outcome analysis and reported later in the record.

  Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

• Number of Participants Who Experienced at Least One Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who experienced at least one AE, for the first pembrolizumab course, was assessed from enrollment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

  Up to ~31 months

• Number of Participants Who Discontinued Study Drug Due to an AE

  An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who discontinued study drug due to an AE, in the first pembrolizumab course, was assessed from enrolment/treatment initiation of a participant and analyzed by Cohort and is reported here for all participants in Cohort A and Cohort B who received ≥1 dose of study drug.

  Up to ~31 months

Secondary Outcomes (10)

• ORR Per RECIST 1.1 by CIV in All Cohort B Participants

  Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

• Duration of Response (DOR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants

  Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

• DOR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression

  Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

• Disease Control Rate (DCR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants

  Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

• DCR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression

  Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

Study Arms (2)

Cohort A: Pembrolizumab

EXPERIMENTAL

Participants in Cohort A previously received at least one prior systemic treatment for metastatic breast cancer. Participants will be administered pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to \~ 2 years).

Biological: Pembrolizumab

Cohort B: Pembrolizumab

EXPERIMENTAL

Participants in Cohort B previously received no prior systemic treatment for metastatic breast cancer AND had a programmed cell death-ligand 1 (PD-L1) positive tumor expression. Participants will be administered pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to \~ 2 years).

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion of 200 mg.

Also known as: MK-3475, KEYTRUDA®

Cohort A: Pembrolizumab; Cohort B: Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For the purposes of this study, neoadjuvant and/or adjuvant chemotherapy regimens do not count as a prior line of therapy.
• For second line plus monotherapy (Parts 1 and 2):
• Has received at least one systemic treatment for metastatic breast cancer
• Has documented disease progression on or after the most recent therapy
• Prior treatment must include an anthracycline and a taxane in the neoadjuvant, adjuvant, or metastatic setting
• For first line monotherapy (Part 1):
• Has received no prior systemic treatment for metastatic breast cancer
• Has PD-L1-positive mTNBC.
• For second line plus monotherapy (Part 2):
• \- Has PD-L1 strong positive mTNBC
• For all parts:
• Has mTNBC confirmed by a central laboratory
• For biomarker analysis, adequate newly obtained core or excisional biopsy of a not-previously-irradiated metastatic tumor lesion (mandatory)
• Has measurable metastatic disease
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• Is currently participating and receiving study treatment, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to study Day 1
• Has received prior anti-cancer monoclonal antibody (mAb) therapy for direct anti-neoplastic treatment within 4 weeks prior to study Day 1
• Has received prior chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks prior to study Day 1
• Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered within at least 2 weeks prior to study Day 1
• Has an active autoimmune disease requiring systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Has known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
• Has radiographically-detectable central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis or a history of interstitial lung disease
• Has an active infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
• Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 \[CTLA-4\], OX-40, CD137) or has participated in Merck MK-3475 (pembrolizumab) study
• Has a known history of human immunodeficiency virus (HIV)
• Has known active Hepatitis B or C

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (5)

• Loi S, Salgado R, Schmid P, Cortes J, Cescon DW, Winer EP, Toppmeyer DL, Rugo HS, De Laurentiis M, Nanda R, Iwata H, Awada A, Tan AR, Sun Y, Karantza V, Wang A, Huang L, Saadatpour A, Cristescu R, Yearley J, Lunceford J, Jelinic P, Adams S. Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis. JCO Precis Oncol. 2023 Apr;7:e2200317. doi: 10.1200/PO.22.00317.

  PMID: 37099733 DERIVED

• Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.

  PMID: 35101941 DERIVED

• Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, Hui R, Curigliano G, Toppmeyer D, O'Shaughnessy J, Loi S, Paluch-Shimon S, Tan AR, Card D, Zhao J, Karantza V, Cortes J. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Ann Oncol. 2019 Mar 1;30(3):397-404. doi: 10.1093/annonc/mdy517.

  PMID: 30475950 DERIVED

• Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan AR, Jia L, Ding Y, Karantza V, Schmid P. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019 Mar 1;30(3):405-411. doi: 10.1093/annonc/mdy518.

  PMID: 30475947 DERIVED

• Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016 Jul 20;34(21):2460-7. doi: 10.1200/JCO.2015.64.8931. Epub 2016 May 2.

  PMID: 27138582 DERIVED

Related Links

• Merck Oncology Clinical Trial Information

MeSH Terms

Conditions

Breast Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: May 18, 2015
• Study Start: June 11, 2015
• Primary Completion: February 18, 2019
• Study Completion: January 31, 2020
• Last Updated: December 16, 2020
• Results First Posted: December 16, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share