Christine Mauz-Körholz1, Kara Kelly2, Frank Keller3, Akash Nahar4, Arun Balakumaran4, Lisa Giulino-Roth5
1 Department of Pediatrics, Justus-Liebig University of Giessen, Giessen, Germany and Medical Faculty of the Martin-Luther-University of Halle-Wittenberg, Halle, Germany, 2 Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center and University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA, 3 Department of Pediatrics, Children's Healthcare of Atlanta and Emory University, Atlanta, GA, USA, 4 Merck & Co., Inc., Kenilworth, NJ, USA, 5 Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA
Objective: High risk for relapse is observed in cHL patients (pts) with SER to initial chemotherapy and the burden of late organ toxicities may be higher following dose intensification. Here, we evaluate the efficacy and safety of pembrolizumab in combination with chemotherapy in patients with cHL and slow early response to frontline chemotherapy.
Methods: The phase 2, open-label KEYNOTE-667 (NCT03407144) study will enroll 400 pts aged 3 to 17 (children) or 18 to 25 years (young adults) with newly diagnosed, confirmed stage IA, IB, or IIA cHL without bulky disease (Group 1 [low-risk]) or stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL (Group 2 [high-risk]); measurable disease; and performance status per Lansky Play-Performance Scale ≥50 (age ≤16 years) or Karnofsky score ≥50 (age >16 years). Pts will receive induction with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD; Group 1) or vincristine, etoposide/etoposide phosphate, prednisone/prednisolone, doxorubicin (OEPA; Group 2) for 2 cycles, followed by early response assessment by PET/CT/MRI. Pts with rapid early response (Deauville score 1–3) will receive standard therapy. Pts with SER (Deauville score 4–5) will receive consolidation with pembrolizumab 2 mg/kg Q3W up to 200 mg (children) or 200 mg Q3W (young adults) plus 2 cycles AVD (Group 1) or 4 cycles cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28; Group 2). PET/CT for late response assessment (LRA) will be performed after consolidation. After LRA, Group 1 pts with SER will receive radiotherapy (RT); in Group 2, pts with Deauville score 4–5 will receive RT. All pts will receive maintenance with pembro Q3W concomitantly with RT. Pembro dosing will continue up to 17 administrations, with an option to stop after 24 weeks due to CR, or until progression, unacceptable toxicity, or withdrawal. The primary endpoint is objective response rate (ORR) per Cheson 2007 IWG criteria by group in SER pts. Secondary endpoints include SERs with PET negativity after consolidation, event-free survival (EFS), overall survival (OS), and radiotherapy frequency and details by group. ORR with 95% CI will be estimated using the Clopper-Pearson method. EFS and OS will be estimated by Kaplan-Meier methods. Safety will be assessed in all treated pts.