Circulating HPV DNA for early detection of minimal residual disease after definitive therapy in oropharyngeal cancer: A phase II biomarker-driven study.

Abstract

6069 Background: Persistent detection of circulating HPV DNA (cfHPVDNA) in plasma following definitive therapy for HPV-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC) is strongly associated with inferior outcomes, including increased risk of relapse and distant metastasis, and defines a high-risk patient population. Immune checkpoint blockade targeting the PD-1 pathway has demonstrated clinically meaningful activity in both curative and palliative settings. We hypothesize that balstilimab, an anti–PD-1 antibody, can induce cfHPVDNA clearance in patients (pts) with persistent ctHPVDNA after definitive treatment and improve long-term disease control. Methods: Eligible pts had HPV+OPSCC, stage I–III per AJCC 8th edition (excluding T1–2N0 and T1–2N1 with lymph nodes <3 cm), and baseline ctHPVDNA (>20 copies/ml) per our institution digital droplet PCR assay. After completion of definitive standard-of-care therapy, ctHPVDNA was assessed at 3- and 6-months. Pts with positive ctHPVDNA test in the absence of radiographic evidence of disease were eligible to receive balstilimab (AGEN2034) at 3 mg/kg intravenously every 2 weeks for 6 months. The primary endpoint was cfHPVDNA clearance rate. Secondary endpoints included time to cfHPV DNA clearance, recurrence-free survival, overall survival, and safety. The study was designed to enroll up to 20 pts using a Bayesian optimal phase II design considering an expected clearance rate of 30%. In order to treat 20 pts, 140 pts would needed to be pre-screened with a baseline positive ctHPVDNA (15% of expected minimal residual disease). Results: A total of 168 pts were pre-screened, of whom 139 were eligible to proceed; disease stage was I, II, and III in 46% (N=64), 28% (N=39), and 26% (N=36) of pts, respectively. The median baseline ctHPVDNA level was 614 copies/mL (range, 26–239,111). A total of 130 of 139 pts had the 3-month ctHPVDNA assessment, as nine have been excluded (loss of follow-up or withdraw consent). Five had a positive ctHPVDNA result, all of whom had radiographic evidence of disease recurrence (3 local, 1 distant, and 1 both local and distant). Among the remaining 125 pts, 100 have completed the 6-month ctHPVDNA assessment. One pt had a positive ctHPVDNA result with radiographic evidence of local recurrence. One patient had a qualitative positive test (<20 copies/ml) without evidence of disease, but the following test prior to trial enrollment was negative. To date, no pts has been allocated to receive balstilimab. Conclusions: Persistent ctHPV DNA positivity without radiographic evidence of disease has not been observed following definitive therapy. These findings suggest that cfHPVDNA surveillance may have limited utility for early detection of minimal residual disease in this setting, thereby challenging the feasibility of ctHPVDNA–guided post-definitive intervention strategies. Clinical trial information: NCT05363709 .