233TiP - KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo + chemo as neoadjuvant followed by pembro vs placebo as ad...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cytotoxic agents
Breast Cancer
Biological therapy
Presenter Peter Schmid
Citation Annals of Oncology (2017) 28 (suppl_5): v68-v73. 10.1093/annonc/mdx364
Authors P. Schmid1, J. Cortes Castan2, J. Bergh3, L. Pusztai4, C. Denkert5, S. Verma6, H.L. McArthur7, J. Zhao8, G. Aktan8, T. Dang8, R. Dent9
  • 1Centre For Experimental Cancer Medicine, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/GB
  • 2Oncology, Ramon y Cajal Hospital, 08035 - Madrid/ES
  • 3Department Of Oncology-pathology, Karolinska Institutet & Cancer Center Karolinska and Karolinska University Hospital, 141 86 - Stockholm/SE
  • 4Medical Oncology, Yale School of Medicine, Yale Cancer Center, New Haven/US
  • 5Pathology, Institut of Pathology, Charité Universtitätsmedizin Berlin, German Cancer Consortium (DKTK) Partner Site Berlin and DKFZ, Heidelberg/DE
  • 6Medical Oncology, Tom Baker Cancer Centre, University of Calgary, T2N 4N2 - Calgary/CA
  • 7Medical Oncology, Cedars-Sinai Medical Center, Los Angeles/US
  • 8Medical Oncology, Merck & Co., Inc., Kenilworth/US
  • 9Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG



Endogenous anticancer immunity may be enhanced with immune checkpoint inhibition by increased tumor-specific antigen release after chemo. Combining the anti–PD-1 inhibitor pembro with chemo may be an effective treatment strategy for TNBC in neoadjuvant and adjuvant settings. KEYNOTE-522 (NCT03036488) is a phase III study of neoadjuvant pembro + chemo followed by adjuvant pembro vs neoadjuvant placebo + chemo followed by adjuvant placebo in pts with TNBC.

Trial design

Eligible pts are aged ≥18 y with previously untreated, centrally confirmed, nonmetastatic TNBC, defined as combined primary tumor (T) and regional lymph node (N) staging per AJCC (investigator-assessed: T1c N1-2, T2-4 N0-2). Pts with bilateral or multifocal primary tumors or inflammatory breast cancer are allowed. ECOG PS 0-1 and adequate organ function are required. Pts with a history of invasive malignancy ≤5 y or prior therapy before study start are excluded. Approximately 855 pts will be randomly assigned to 1 of 2 arms and stratified by tumor nodal status (positive vs negative), size (T1/T2 vs T3/T4), and carboplatin choice (Q3W vs QW). In arm 1, pts will receive 4 cycles of pembro 200 mg Q3W + paclitaxel (80 mg/m2 QW on d 1, 8, 15) + carboplatin (AUC 5 Q3W on d 1 or AUC 1.5 QW on d 1, 8, 15) and then 4 cycles of pembro + doxorubicin (60 mg/m2 on d 1) or epirubicin (90 mg/m2 on d 1) + cyclophosphamide (600 mg/m2 Q3W on d 1) as neoadjuvant therapy. Definitive surgery will be 3-6 wk after the last cycle. In arm 2, placebo will replace pembro. Post-surgery, pts will receive 9 cycles of pembro or placebo as adjuvant therapy. One neoadjuvant/adjuvant cycle = 21 d; treatment is up to 17 cycles (pembro/placebo only) or until disease progression/unacceptable toxicity. Dual primary endpoints are pCR rate (ypT0/Tis ypN0) and EFS. Secondary endpoints include pCR rate (ypT0 ypN0) in all pts and in those with PD-L1+ tumors (ie, PD-L1 staining in ≥ 1% tumor cells or stroma), pCR rate (ypT0/Tis ypN0) in pts with PD-L1+ tumors, EFS in pts with PD-L1+ tumors, pCR rate (ypT0/Tis) in all pts and in those with PD-L1+ tumors, OS, and safety. Interim analyses are planned.

Clinical trial identification

EUDRACT number: 2016-004740-11 ClinicalTrials.gov, NCT03036488, January 27, 2017

Legal entity responsible for the study

Merck & Co., Inc., Kenilworth, NJ, USA


Merck & Co., Inc., Kenilworth, NJ, USA


P. Schmid: Honoraria: Pfizer, Boehringer, Bayer, Puma, Eisai, Celgene. Other: spouse: Genetech/Roche. J. Cortes Castan: Advisory board member: Roche, Celgene, Aztrazeneca, Cellestia Biotech, Biothera. Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer. J. Bergh: Research funding; grants: Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche and Sanofi-Aventis to Karolinska Institutet/University Hospital. No personal payments. Honoraria: from UpToDate to Asklepios Medicine HB on a chapter on breast cancer diagnostics. L. Pusztai: Advisory board: Merck, Novartis, AstraZeneca. Research funding: Merck, Novartis, Roche, AstraZeneca, Seattle Genetics. Honoraria: Merck. C. Denkert: Stock ownership: Sividon Diagnostics, Cologne. Advisory board: MSD. Honoraria: Amgen, Celgene, Teva, AstraZeneca, Myriad. S. Verma: Advisory board: Amgen, Eli Lilly, AstraZeneca, Novartis, Pfizer, Roche. H.L. McArthur: Advisory board: Celgene, Merck, OBI, Spectrum Pharmaceuticals, Syndax Pharmaceuticals, Roche, Peregrine, Calithera. J. Zhao: Employment: Merck Research Lab. G. Aktan: Employment, stocks, travel: Merck & Co., Inc. T. Dang: Employment and stock: Merck Sharp & Dohme. R. Dent: Advisory board: AstraZeneca, Pfizer, Roche, Merck. Research funding: AstraZeneca. Honoaria: Eisai, Roche, Pfizer. Travel expenses: Roche, Merck, Pfizer.