Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Phase 3, randomized, double-blind, placebo-controlled study of Pembrolizumab+Chemotherapy in patients with HR+/HER2− locally recurrent inoperable or metastatic breast cancer (mBC): KEYNOTE-B49 (#452)

Peter Schmid 1 , Joo Hyuk Sohn 2 , Yolanda Jerez Gilarranz 3 , Lucia Gonzalez-Cortijo 4 , Amir Sonnenblick 5 , Dhanusha Sabanathan 6 , Ernesto Korbenfeld 7 , Daniel Egle 8 , Brigitte Poirier 9 , Flora Zagouri 10 , Alexios Matikas 11 , Sercan Aksoy 12 , Umut Demirci 13 , Pier Ramos-Elias 14 , Seock-Ah Im 15 , Fatima Cardoso 16 , Liyi Jia 17 , Kim Hirshfield 17 , Konstantinos Tryfonidis 17 , Hope S. Rugo 18
  1. Barts Cancer Institute, Centre for Experimental Cancer Medicine, Queen Mary University of London, Charterhouse Sq., London EC1M 6BQ, UK
  2. Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
  3. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM); Medical Oncology Department, Hospital General Universitario Gregorio Marañón; Universidad Complutense de Madrid and CiberOnc, Madrid, Spain
  4. Medical Oncology Department, Hospital Universitario Quirónsalud, Madrid, Spain
  5. Oncology Division, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  6. Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia
  7. Hospital Británico de Buenos Aires-Oncology, Buenos Aires, Argentina
  8. Landeskrankenhaus - Universitätskliniken Innsbruck, Innsbruck, Austria and Medizinische Universitaet Innsbruck, Innsbruck, Austria
  9. Hopital Du Saint-Sacrement, Quebec City, QC, Canada
  10. Alexandra Hospital-ONCOLOGY DEPT, Athens, Greece
  11. Karolinska Universitetssjukhuset Solna-Tema Cancer - ME Bröst- endokrina tumörer och sarkom, Stockholm, Sweden
  12. Hacettepe University Cancer Institute, Department of Medical Oncology, Ankara, Turkey
  13. Memorial Ankara Hospital, Medical Oncology, Balgat, Ankara, Turkey
  14. Medical Oncology, INTEGRA Cancer Institute, Guatemala City, Guatemala
  15. Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
  16. Breast Unit, Champalimaud Clinical Centre/Champalimaud Foundation, Lisbon, Portugal
  17. Merck & Co., Inc., Rahway, NJ, USA
  18. Division of Hematology and Oncology, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA

Aims: The phase 1b KEYNOTE-028 trial showed durable activity with pembrolizumab monotherapy in previously treated HR+/HER2−, PD-L1–positive (combined positive score [CPS] ≥1) advanced breast cancer. KEYNOTE-B49 (NCT04895358) is a phase 3, double-blind study of pembrolizumab+chemotherapy vs placebo+chemotherapy in PD-L1–positive, HR+/HER2− locally recurrent inoperable or mBC after progression on prior endocrine therapy.

Methods: ⁓800 patients with HR+/HER2− locally recurrent inoperable or mBC who are candidates for chemotherapy (no prior chemotherapy for metastatic disease) with PD-L1 CPS ≥1 and documented PD on prior endocrine therapy will be enrolled. Prior endocrine therapy comprises ≥2 lines (≥1 in combination with a CDK4/6 inhibitor) in the metastatic setting (group 1); or 1 line with CDK4/6 inhibitor treatment for mBC in patients with relapse ≤24 months of primary surgery while on adjuvant endocrine therapy (group 2a); or PD ≤12 months of starting endocrine therapy with CDK4/6 inhibitor for metastatic disease (group 2b). Patients without prior CDK4/6 inhibitor treatment may enroll if they had PD ≤6-months of starting endocrine therapy for metastatic disease and previously relapsed ≤24-months of primary tumor surgery while on adjuvant endocrine therapy (group 3). Patients are randomized 1:1 to pembrolizumab 200 mg IV or placebo Q3W, each in combination with investigator’s choice of chemotherapy: paclitaxel 90 mg/m2 IV on days (D) 1/8/15 Q4W; nab-paclitaxel 100 mg/m2 IV on D1/8/15 Q4W; liposomal doxorubicin 50 mg/m2 IV on D1 Q4W; or capecitabine 1000 mg/m2 PO BID on D1–14 Q3W. Treatment continues until PD, unacceptable toxicity, withdrawal, or, for pembrolizumab/placebo, completion of 35 cycles (~2y); chemotherapy can continue per investigator discretion. Radiologic assessments are performed Q9W for 54 weeks and Q12W thereafter. Primary endpoints are PFS per RECIST v1.1 by BICR and OS in patients with PD-L1 CPS ≥10 and ≥1 tumors, separately. Enrollment is ongoing at 204 international sites.