Transparency Submission

FDA Clearance: N/A

Rationale for Requested Change: In light of the limitations of response assessment with PET scan alone, current guidelines include the recommendation of a repeat biopsy in the setting of a partial response or progressive disease (PET-positive) at the end of 1L therapy to confirm residual or recurrent disease. However, the current guidelines acknowledge that repeat biopsy is not always possible. Published data across numerous manuscripts and presentations have demonstrated the prognostic performance of Foresight’s MRD test using PhasED-Seq-technology in large B-cell lymphomas (LBCLs) [2-12]. The analytical performance of Foresight’s MRD test has also been demonstrated to be robust and reproducible with an analytical limit of detection below 1 in 1,000,000 and a false positive rate of less than 1% [1]. Though there are multiple emerging MRD tests in lymphoma, only Foresight’s MRD test has demonstrated the robust analytical validity [1] and clinical validity [2-12] necessary to support clinical use. Published data demonstrates that the Foresight CLARITY test is prognostic in patients who are PET-positive at the end of 1L therapy. Specifically, Sworder et al. demonstrated that patients who are positive by both PET-CT and Foresight’s ctDNA-MRD assessment have significantly worse outcomes than PET-CT positive patients who are ctDNA-MRD negative [reference 11, slides 11 and 13]. This demonstrates that ctDNA-MRD positivity correctly identifies true positive PET-CT scans, while ctDNA-MRD negativity identifies likely false positive PET-CT scans. This suggests that it would be clinically appropriate to proceed to additional treatment per BCEL-7 in the ctDNA-MRD positive patients and that additional short interval surveillance would be clinically appropriate in the ctDNA-MRD negative patients. Collectively, we believe this data demonstrates that the Foresight CLARITY test provides robust and reliable results for clinical use and provides sufficient prognostic information in patients with PET-positive results at end of therapy to be used in addition to, or as an alternative to biopsy in this setting. Moreover, MRD testing offers additional clinical utility in patients for whom a biopsy is not feasible, which remains a difficult clinical scenario with imperfect options.