An Open-Label, Uncontrolled, Multicenter Phase II Trial of MK-3475 (Pembrolizumab) in Children and Young Adults with Newly Diagnosed Classical Hodgkin Lymphoma with Inadequate (Slow Early) Response to Frontline Chemotherapy (KEYNOTE 667)

An Open-Label, Uncontrolled, Multicenter Phase II Trial of MK-3475 (Pembrolizumab) in Children and Young Adults with Newly Diagnosed Classical Hodgkin Lymphoma with Inadequate (Slow Early) Response to Frontline Chemotherapy (KEYNOTE 667) Treatment of cHL in children and young adults – evaluation of pembrolizumab in a subgroup with inadequate early response to frontline chemotherapy. The Sponsor estimates that the study will require approximately 6 years from the time the first participant signs the informed consent/assent until the last participant’s last study-related contact or visit. Group 1 (low risk) defined as participants with cHL stages IA, IB and IIA without bulky disease. After completing 2 cycles of ABVD induction chemotherapy, those with a Deauville score of 4 or 5 (ie, SERs), as assessed by PET, will receive pembrolizumab 2 mg/kg up to a max of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) Q3W, in combination with 2 cycles of AVD (doxorubicin 25 mg/m2, vinblastine 6 mg/m2 and dacarbazine 375 mg/m2 on days 1 and 15; cycle frequency: Q4W). Slow early responders will have their PET response assessed again after completing AVD chemotherapy. All SERs will then receive RT while continuing their pembrolizumab treatment. Group 2 (high risk) defined as participants with cHL stages IIEB, IIIEA, IIIEB, IIIB, IVA and IVB. After completing 2 cycles of OEPA induction chemotherapy, those with a Deauville score of 4 or 5 (ie, SERs), as assessed by PET, will receive pembrolizumab 2 mg/kg Q3W up to a max of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) Q3W, in combination with 4 cycles of COPDAC-28 (cyclophosphamide 500 mg/m2 on days 1 and 8, vincristine 1.5 mg/m2 with max. single dose 2 mg on days 1 and 8, prednisone/prednisolone 40 mg/m2/day divided in 3 doses on days 1 to 15, dacarbazine 250 mg/m2 on days 1 to 3; cycle frequency: Q4W). Slow early responders will have their PET response assessed again after completing COPDAC-28 chemotherapy. Those with a positive PET response (ie, Deauville score of 4 or 5) will then receive RT while continuing their pembrolizumab treatment. Slow early responders with a negative PET response will continue their pembrolizumab treatment without receiving RT. Rapid early responders (RERs) in both groups will not receive additional study treatment and will be treated with non-study consolidation chemotherapy (eg, 2 cycles of ABVD for Group 1 and 4 cycles of COPDAC-28 for Group 2) at investigator’s discretion.