Foresight Diagnostics, in collaboration with the University of Washington School of Medicine and Fred Hutch Cancer Center, has launched the PRECISE-HL clinical trial to investigate whether chemotherapy exposure can be safely reduced in patients with advanced-stage classical Hodgkin lymphoma (cHL) who show early response to treatment.
The innovative trial will utilize Foresight's CLARITY laboratory-developed test (LDT), which employs PhasED-Seq technology to detect circulating tumor DNA (ctDNA) with ultra-sensitive precision. This approach aims to overcome limitations of traditional response assessment methods like PET/CT scans, which can yield false positives and negatives in cHL patients.
Trial Design and Treatment Approach
Patients with newly diagnosed advanced-stage cHL will receive two cycles of nivolumab combined with AVD therapy (doxorubicin, vinblastine, and dacarbazine). Following this initial treatment, patients will undergo interim assessment using the Foresight CLARITY test to measure minimal residual disease (MRD).
The treatment path will then diverge based on ctDNA results:
- Patients with undetectable ctDNA will receive only four cycles of nivolumab plus AVD before transitioning to nivolumab monotherapy for two additional cycles
- Patients with detectable ctDNA will continue with the full six cycles of nivolumab plus AVD
End-of-therapy ctDNA-MRD analysis will also be conducted as an exploratory endpoint to further assess treatment efficacy.
Addressing Unmet Needs in Hodgkin Lymphoma Treatment
The standard treatment for newly diagnosed advanced cHL currently involves multiple cycles of chemotherapy, which can lead to significant long-term side effects despite high cure rates.
"Building on two promising breakthroughs—the remarkably high rate of early response to combination immunochemotherapy and our ability to detect this response through ultra-sensitive ctDNA-MRD testing—we are now launching a prospective study to investigate whether we can safely reduce chemotherapy for these early responders while maintaining long-term efficacy," said Dr. Ryan Lynch, principal investigator of the study and associate professor at the University of Washington School of Medicine.
Research from the University of Washington has shown that more than 70% of patients reached undetectable MRD by the end of cycle two when treated with a PD-1 inhibitor and chemotherapy combination. This suggests that a significant proportion of patients might benefit from reduced chemotherapy exposure.
Potential to Transform Treatment Paradigm
"The PRECISE-HL trial represents a significant milestone in our pursuit of using MRD to personalize therapy for patients," said Dr. David Kurtz, Chief Medical Officer and Head of Research at Foresight Diagnostics. "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."
The performance of Foresight's CLARITY technology enables researchers to explore more personalized treatment approaches that were previously not feasible. By tailoring therapy duration based on individual patient response, this approach has the potential to transform cHL treatment, potentially improving both outcomes and quality of life.
Broader Implications for Precision Medicine
The PRECISE-HL trial represents part of a growing trend toward using molecular biomarkers to guide treatment decisions in oncology. Recent studies have explored combining new therapies, such as PD-1 inhibitors like nivolumab, with chemotherapy to potentially improve long-term outcomes in Hodgkin lymphoma.
If successful, this approach could establish a new paradigm for treatment de-escalation strategies across various cancer types, where therapy intensity is adjusted based on early molecular response rather than predetermined protocols.
For patients with cHL, the potential to maintain efficacy while reducing exposure to chemotherapy could significantly decrease long-term complications such as cardiotoxicity, neuropathy, and secondary malignancies that can affect survivors' quality of life for decades after treatment.
The trial is currently enrolling patients, and detailed information about eligibility and protocol can be found on ClinicalTrials.gov.
