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 Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Locally Advanced
Breast Cancer
Cancer Immunology and Immunotherapy
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.