Abstract P103

Updated Results From the Phase 2 KEYNOTE-667 Study: Pembrolizumab (pembro) in Children and Young Adults With High-Risk Classical Hodgkin Lymphoma (cHL) With Slow Early Response (SER) to Front-Line Chemotherapy (chemo)

Background: KEYNOTE-667 (NCT03407144) is evaluating pembro + chemo consolidation +/- involved site radiotherapy (ISRT) followed by pembro maintenance in pts with cHL and SER to front-line chemo. Prior results for pts with high-risk cHL and SER to vincristine, etoposide, prednisone/prednisolone, and doxorubicin (OEPA) induction showed consolidation with pembro + cyclophosphamide, vincristine, prednisone/prednisolone, and dacarbazine (COPDAC-28) followed by pembro maintenance had manageable safety and promising activity, and 71% had a PET-negative response per BICR (1 pt ended up receiving RT). Here, we present additional follow up of pts with high-risk cHL and SER to OEPA.

Methods: Pts aged 3-25 y with newly diagnosed stage IIEB to IVB cHL received 2 cycles of OEPA followed by early response assessment (PET and CT/MRI). Pts with rapid early response received nonstudy therapy. Pts with SER (ie, Deauville score [DS], 4 or 5) received consolidation with pembro 2 mg/kg up to 200 mg (3-17 y) or 200 mg (18-25 y) IV Q3W + 4 cycles of COPDAC-28 followed by LRA (PET, CT/MRI). Pts with PET positivity at LRA (ie, DS 4 or 5) received ISRT (28.8 Gy) to late PET-positive residua; pts with PET negativity received no ISRT. All pts received maintenance pembro ≤17 cycles. Primary end point was ORR by BICR per Cheson 2007 IWG criteria. Secondary end points included PET negativity after COPDAC-28 and safety.

Results: 84 pts with high-risk cHL and SER to OEPA were included. Median follow-up at data cutoff (Feb 29, 2024) was 24.3 mo (range, 5.7-48.4). 55 pts completed consolidation and maintenance, 20 were ongoing, and 9 discontinued. Pts received a median of 17 doses of pembro (range, 2-17); median time on pembro was 11.1 mo (range, 0.5-11.8). 80 pts (95%) had a LRA, of whom 56 (70%) were PET negative by BICR (55 [69%] PET negative by investigator). ORR in pts with a post baseline assessment (n = 80) was 99% (95% CI, 93-100; CR 57/PR 22). Treatment-related AEs (TRAEs) occurred in 61 pts (73%; grade 3 or 4 in 16 pts [19%]). 3 pts (4%) discontinued treatment due to TRAEs. No pts died due to TRAEs. 10 pts (12%) had immune-mediated AEs.

Conclusion: With median 24 mo follow-up, consolidation with pembro + COPDAC-28 +/- ISRT followed by pembro maintenance continued to have manageable safety and promising activity in pts with high-risk cHL and SER to front-line OEPA. Among pts with a LRA, 70% were PET negative by BICR; 69% were PET negative by investigator review and spared RT.

Authors

Christine Mauz-Körholz, Luciana Vinti, Stephen Daw, Antony Ceraulo, Gerard Michel, Michaela Cepelova, Constantino Sabado Alvarez, Franca Fagioli, Stephane Ducassou, Salvatore Buffardi, Thierry Leblanc, Bradford S. Hoppe, Frank G. Keller, Kara M. Kelly, Lisa Giulino-Roth, Judith Landman-Parker, Juan Shen, Pallavi Pillai, Rushdia Yusuf, Auke Beishuizen