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.