Abstract P087

AHOD2131: A Randomized Phase 3 Response-Adapted Trial Comparing Standard Therapy with Immuno-oncology Therapy for Children & Adults with Newly Diagnosed Stage I & II Classic Hodgkin Lymphoma

Background: Chemotherapy (CT) in combination with radiotherapy (RT) is the current frontline standard for early-stage (ES) classic Hodgkin lymphoma (HL), with cure rates of >90%. Recently, novel treatments have aimed to maintain high cure rates while minimizing acute and long-term toxicities associated with CT and RT. Incorporation of novel immunotherapy (IO) agents into frontline settings offer new potential therapy options that may reduce exposure to CT and RT while improving progression-free survival (PFS) and maintaining overall survival (OS).

Methods: AHOD2131 (NCT05675410) was collaboratively developed between pediatric and adult oncology members of the National Cancer Institute’s National Clinical Trial Network (NCTN), aiming to harmonize frontline IO-based treatment approaches for ES HL. Study champions from each North American cooperative group (NACGs) (Children’s Oncology Group [COG], SWOG, ECOG-ACRIN, Alliance, NRG) and experts in imaging, radiation oncology, HL biology and patient-reported outcomes (PROs) were included in the development. AHOD2131 is a randomized, phase 3 trial for patients ages 5 to 60 years with newly diagnosed stage I/II HL, investigating the addition of brentuximab vedotin (Bv) with nivolumab compared to standard CT +/- RT. The primary objective is to compare PFS of patients treated through a response-adapted, superiority design with either standard or IO (i.e. BV/Nivo) therapies. There are 11 secondary and exploratory study aims. 12-year OS is a key secondary aim. AHOD2131 was activated in April 2023 with a target enrollment of 1875 patients over 5 years. Patients are initially stratified as favorable or unfavorable risk. All patients receive 2 cycles of ABVD followed by interim PET2 (central review). Patients who are PET2 positive (slow early response [SER]) undergo separate randomizations compared to those who are PET2 negative (rapid early response [RER]). SERs receive involved site RT after completion of further systemic therapy while those with RER receive systemic therapy only (Figure).

Results: As of 28 April 2026, 395 sites have activated, and 838 participants have enrolled. To date, 49% are <18 years old and 65% are ES unfavorable risk.

Conclusion: This COG-led pan-NCTN trial will be the largest study for ES HL in the history of NACGs. AHOD2131 strengthens the effort between NACGs to conduct collaborative clinical trials and aims to harmonize an improved standard of care for ES HL across the age continuum.