Abstract 1878
Background
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
Funding
Merck & Co., Inc., Kenilworth, NJ, USA
Disclosure
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.