Abstract P052

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

*JS, BH co-first authors

Background: Chemotherapy in combination with radiotherapy (RT) is the standard for early-stage (ES) classic Hodgkin lymphoma (cHL). Despite excellent cure rates, there is room to improve outcomes for children and adults with ES cHL. Incorporation of immunotherapy (IO) into front line treatment may improve progression-free survival (PFS) and maintain overall survival, while minimizing morbidity and mortality by reducing RT and high-dose chemotherapy.

Methods: HL leaders of the pediatric and medical oncology National Cancer Institute’s National Clinical Trial Network groups, collaborated to harmonize treatment approaches for ES cHL and to reach consensus around optimal study design for incorporating IO into frontline treatment. Study champions from each North American (NA) cooperative group [Children’s Oncology Group (COG), SWOG, ECOG-ACRIN, Alliance, NRG] and experts in imaging, radiation oncology, lymphoma biology and patient-reported outcomes were included. The resulting COG-led clinical trial, AHOD2131, represents the largest ES cHL trial in the history of NA cooperative groups and the first to enroll patients across the age continuum.

Results: AHOD2131 (NCT05675410; Figure) is a randomized, phase 3 trial for patients ages 5 to 60 years with newly diagnosed stage I and II cHL, investigating the addition of the CD30-antibody drug conjugate brentuximab vedotin (Bv) with PD-1 blockade (nivolumab) compared to standard chemotherapy +/- RT. As of 7 May 2024, 208 sites have activated, and 195 participants have enrolled. Target enrollment is 1875 patients over 5 years.

The primary objective is to compare the 3-year PFS of patients treated through a response-adapted, superiority design with either standard therapy or IO (BV + nivolumab). Patients will be stratified based on favorable or unfavorable risk features at enrollment. Based on response assessment by PET/CT (central review) after 2 cycles of ABVD, patients will be classified to PET2 positive (SER, defined as 5-Point Deauville Score 4 or 5) or PET2 negative (RER). Patients with SER will receive involved site RT. SER and RER patients will be randomized to standard chemotherapy vs. IO respectively. There are 11 secondary and 10 exploratory aims. 12-year OS is a key secondary aim.

Conclusion: AHOD2131 strengthens the effort between NA cooperative groups to conduct collaborative clinical trials and aims to harmonize an improved standard of care for ES cHL across the age continuum.

Authors

Jennifer Seelisch, Boyu Hu, Lindsay A. Renfro, Frank G. Keller, Adam DuVall, Tara O. Henderson, Yue Wu, Steve Yoon-Ho Cho, Bradford S. Hoppe, Sarah Milgrom, Lisa Giulino Roth, Natalie S. Grover, Ann S. LaCasce, Justine M. Kahn, Song Yao, Susan K. Parsons, Niloufer Khan, Raymond Mailhot Vega, Pamela S. Hinds, Pamela B. Allen, Andrew M. Evens, Heiko Schoder, Sharon M. Castellino, Kara M. Kelly