285TiP - Phase II, 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

Background

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

Trial design

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.

Clinical trial identification

NCT03407144.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

K. Kelly: Research grant / Funding (institution): Merck & Co., Inc. F. Keller: Research grant / Funding (institution): Merck & Co., Inc. A. Nahar: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. L. Giulino-Roth: Research grant / Funding (institution): Merck & Co., Inc. All other authors have declared no conflicts of interest.