Klin Padiatr 2020; 232(02): 83
DOI: 10.1055/s-0040-1701823
S-II
Session II: Immune Checkpoint Inhibition and Drug Targets
© Georg Thieme Verlag KG Stuttgart · New York

Phase 2, open-label study of pembrolizumab in children and young adults with newly diagnosed classical hodgkin lymphoma (cHL) with slow early response (SER) to frontline chemotherapy: KEYNOTE-667

C Mauz-Körholz
1   Justus-Liebig University of Giessen, Giessen, Germany
,
KM Kelly
2   Roswell Park Comprehensive Cancer Center and University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, USA
,
FG Keller
3   Children’s Healthcare of Atlanta and Emory University, Atlanta, USA
,
R Ramchandren
4   Karamos Cancer Institute, Detroit, USA
,
A Nahar
5   Merck & Co., Inc., Kenilworth, USA
,
L Giulino-Roth
6   Weill Cornell Medical College, New York, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
18 March 2020 (online)

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    Introduction High risk for relapse is observed in cHL patients (pts) with SER to initial chemotherapy and organ toxicities may be higher following dose intensification.

    Methods The phase 2 KEYNOTE-667 (NCT03407144) study will enroll 440 pts aged 3-17 (children) or 18-25 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; 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, then early response assessment by PET/CT/MRI. Pts with rapid early response (Deauville score 1-3) will receive non-study consolidation chemotherapy. Pts with SER (Deauville score 4-5) will receive consolidation with pembro 2 mg/kg Q3W 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 SER pts and Group 2 pts (Deauville score 4-5) will receive radiotherapy (RT). All pts will receive maintenance pembro Q3W concomitantly with RT. Pembro will continue for 17 administrations, with option to stop after 8-administrations due to CR, or until progression, unacceptable toxicity, or withdrawal. Primary endpoint: ORR per Cheson 2007 IWG criteria by group in SER pts. Secondary endpoints: SERs with PET negativity after consolidation, 2-yr event-free survival (EFS), OS, RT frequency and details by group, RERs with PET negativity after ABVD induction, 3-yr EFS by investigator, OS by risk group, serum TARC levels at screening in SERs by risk group. ORR with 95% CI will be estimated by Clopper-Pearson method. EFS and OS will be estimated by Kaplan-Meier method. Safety will be assessed in all-treated pts.

    Results N/A

    Conclusion N/A


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    Conflict of Interest:

    Dr. Mauz-Körholz declares no conflicts. Drs. Kelly Giulino have received research grants from Merck & Co., Inc., to their respective institutions. Drs. Keller and Ramchandren have received research funding from Merck & Co., Inc. Mr Nahar is an employee of Merck & Co., Inc., and may own stock in the company.