PHASE 2 KEYNOTE‐667: PEMBROLIZUMAB IN CHILDREN AND YOUNG ADULTS WITH CLASSICAL HODGKIN LYMPHOMA (CHL) WITH SLOW EARLY RESPONSE TO FRONT‐LINE CHEMOTHERAPY

Introduction: Patients (pts) with cHL with slow early response (SER) to initial chemotherapy (chemo) have a high risk of relapse. Current treatments such as chemo dose intensification and radiotherapy (RT) can increase the risk of secondary malignancies and cause long-term toxicity. KEYNOTE-667 (NCT03407144) is an open-label, phase 2 study being conducted to evaluate pembrolizumab (pembro) plus chemo in pts with cHL and SER to front-line chemo. We present results of an interim analysis of pts with high-risk cHL and SER (group 2). Methods: Pts eligible for group 2 were aged 3–17 (children) or 18–25 y (young adults) with newly diagnosed high-risk (stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB) cHL. Pts in group 2 received induction therapy with 2 cycles of vincristine, etoposide, prednisone/prednisolone, and doxorubicin (OEPA). Response was then assessed by PET/MRI/CT. Pts with rapid early response to OEPA received nonstudy therapy and pts with SER to OEPA (Deauville score, 4/5) received consolidation with 4 cycles of cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28) plus pembro 2 mg/kg up to 200 mg IV Q3W (3–17 y) or 200 mg IV Q3W (18–25 y). After consolidation, pts with PET positivity (Deauville score, 4/5 at late response assessment [LRA]) received involved-site RT (28.8 Gy) to late PET-positive residua. RT was omitted in pts with PET negativity. All pts with SER continued to receive pembro Q3W for 17 doses. The primary end point was ORR in pts with SER by blinded independent central review (BICR) per Cheson 2007 International Working Group criteria. Secondary end points included PET negativity at LRA and safety. Results: 49 pts with high-risk cHL with SER to OEPA were included in group 2. The median age was 15 y (range, 6–22), 24 pts (49%) had bulky disease, and 31 (63%) had Ann Arbor stage IV disease. At data cutoff (2 September 2022), the median follow-up was 15.3 mo (range, 3.2–30.5); 22 pts (45%) had completed treatment and 24 (49%) were ongoing on consolidation/maintenance. Median time on pembrolizumab was 10.4 mo (range, 0.5–11.8). 42 pts (86%) had an LRA, of whom 27 (64%) were PET negative by BICR (30 pts [71%] were PET negative by investigator review). Adverse events (AEs) occurred in 42 pts (86%), with grade 3/4 AEs in 13 pts (27%). Serious AEs were reported in 7 pts (14%). No pts died because of an AE. Treatment-related AEs occurred in 30 pts (61%), with grade 3/4 treatment-related AEs in 6 pts (12%). 4 pts (8%) had immune-mediated AEs: 2 grade 1 hypothyroidism and 2 grade 2 hypothyroidism. Conclusions: The results showed that pembro plus COPDAC-28 consolidation had manageable safety and promising efficacy in children and young adults with high-risk cHL and SER to front-line chemo. 64% of pts with a LRA had a PET-negative response and were spared RT. These findings suggest that adding pembro to COPDAC-28 consolidation may augment responses in this high-risk cHL population. Encore Abstract - previously submitted to ASCO 2023 and EHA 2023 The research was funded by: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Keywords: Hodgkin lymphoma, immunotherapy Conflicts of interests pertinent to the abstract L. Vinti Consultant or advisory role: Amgen, Clinigen Research funding: Merck, Sharp & Dohme Educational grants: Takeda, Neon Other remuneration: Amgen, Takeda F. Fagioli Employment or leadership position: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi Consultant Or Advisory Role: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi Honoraria: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi Educational Grants: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi Other Remuneration: Takeda, Novartis, Jazz Pharmaceuticals, Sanofi D. Plaza Lopez de Sabando Research funding: MERCK J. Landman-Parker Research funding: BMS, MSD J. Shen Employment or leadership position: Merck P. Pillai Employment or leadership position: Merck Stock ownership: Merck P. Marinello Employment or leadership position: Merck Stock ownership: Merck C. Mauz-Koerholz Consultant or advisory role: MSD Research funding: MSD