Foresight Diagnostics has initiated the PRECISE-HL trial to investigate the potential for therapy de-escalation using ctDNA-based methods in classical Hodgkin lymphoma (cHL).
In this connection, the cancer diagnostics company is collaborating with the University of Washington School of Medicine and the Fred Hutch Cancer Center in Seattle.
The study employs Foresight Diagnostics’ CLARITY laboratory developed test (LDT), which utilises circulating tumour DNA (ctDNA) for minimal residual disease (MRD) detection. Its aim is to personalise treatment for advanced-stage cHL patients.
The primary goal is to assess whether chemotherapy exposure can be reduced for those showing an early response.
Foresight Diagnostics chief medical officer and research head David Kurtz said: “The PRECISE-HL trial represents a significant milestone in our pursuit of using MRD to personalise therapy for patients. This study complements the SHORTEN-ctDNA trial in diffuse large B-cell lymphoma (DLBCL), that Foresight Diagnostics is also supporting, in seeking to reduce patient exposure to chemotherapy.
“Foresight CLARITY LDT with ultra-sensitive MRD detection capabilities helps overcome the limitations of traditional response assessment methods like PET/CT, which can yield false positives and negatives in cHL. The performance of the Foresight CLARITY technology enables us to research more personalized treatment approaches that were previously not feasible.”
Currently, standard treatment protocols for newly diagnosed advanced cHL involve several cycles of chemotherapy. Recent research is exploring the integration of novel therapies, such as PD-1 inhibitors like nivolumab, with chemotherapy to potentially improve long-term patient outcomes.
A study by the University of Washington School of Medicine found that over 70% of patients achieved undetectable MRD by the end of two chemotherapy cycles when treated with a combination regimen including a PD-1 inhibitor. Despite these results, existing guidelines recommend extended chemotherapy, which can result in prolonged side effects.
In the PRECISE-HL trial, patients newly diagnosed with advanced-stage cHL will initially receive two cycles of a combination therapy involving nivolumab and AVD (doxorubicin, vinblastine, dacarbazine).
An interim assessment using the Foresight CLARITY LDT will determine future treatment directions. Patients with undetectable ctDNA will proceed to two cycles of nivolumab monotherapy after completing four cycles of nivolumab + AVD.
Those with detectable ctDNA will continue with the complete six-cycle regimen. The trial also includes an exploratory endpoint focusing on end-of-therapy ctDNA-MRD analysis.
