Abstract P009

PRECISE-HL Trial: Personalized Reduction of Chemotherapy Intensity through ctDNA Evaluation in Advanced Hodgkin Lymphoma

Introduction:

Nivolumab-AVD has become a new standard for untreated advanced stage Hodgkin lymphoma in North America. The PRECISE-HL trial will assess a response-adaptive CHL treatment approach utilizing PhasED-Seq to reduce the overall chemotherapy burden for patients with early MRD-negativity when treated with nivolumab-AVD (NCT06745076).

Methods:

This is a multi-center phase 2, open label pilot study of six cycles of response-adapted therapy based on MRD testing by PhasED-Seq for untreated stage III or IV CHL. Patients will receive the combination of nivolumab (240 mg IV), doxorubicin (25 mg/m2 IV), vinblastine (6 mg/m2 IV) dacarbazine (375 mg/m2 IV) on days 1 and 15 of 28-day cycles.

Blood samples for PhasED-Seq testing at baseline and post cycle 2 will be sent to Foresight Diagnostics for rapid processing (estimated turn-around time 10-14 days). For patients with undetectable MRD at cycle 3 day 1, the doxorubicin, vinblastine, and dacarbazine will be removed from Cycle 5 and Cycle 6 while continuing nivolumab. For patients with detectable or inconclusive MRD, treatment after interim assessment will continue with all 4 agents for 6 total cycles.

Planned enrollment is 125 patients. The primary endpoint is 1-year PFS in patients with undetectable MRD after 2 cycles of treatment. Secondary endpoints include 1-year PFS in MRD positive patients after 2 cycles of treatment, 2-year PFS in the overall cohort and stratified by MRD status, and best overall response as complete or partial response (CR/PR). Exploratory endpoints include MRD assessments at other timepoints and during follow up, patient reported outcomes, and cardiac biomarkers.

The primary efficacy benchmark for this trial is a 1-year progression-free survival (PFS) rate of ≥94% for interim ctDNA negative patients based on historical data from the S1826 study.

Additional key eligibility criteria include age 18+ and measurable disease per Lugano criteria. Key exclusion criteria include current or prior autoimmune disease except vitiligo or thyroid disease on stable replacement doses.