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Purpose: We evaluated ctDNA as a pharmacodynamic and predictive biomarker in patients (pts) with resectable HCC treated with cemiplimab (anti-programmed cell death-1). Background: A biomarker-focused study of neoadjuvant cemiplimab in resectable HCC demonstrated acceptable safety and pathologic responses that were associated with immune signatures of intratumoral T-cell response (Marron TU et al. Lancet Gastroenterol. Hepatol. 2022). ctDNA is emerging as a tool to monitor therapy responses and predict RFS in perioperative HCC studies. Methods: We enrolled 21 pts who received 2 cycles of neoadjuvant cemiplimab (350 mg intravenous every 3 weeks), followed by surgical resection and 8 cycles of adjuvant cemiplimab (NCT03916627). The primary endpoint was significant tumor necrosis (STN; >70% necrosis). Secondary endpoints included safety, RFS, and overall survival. A post hoc analysis examined pathological response (≥50% necrosis). Pts underwent pretreatment biopsies and longitudinal blood collection for ctDNA analyses using bespoke multiplex PCR-next generation sequencing (Signatera). We evaluated correlatives of ctDNA changes and the prognostic value undetectable ctDNA after surgery on RFS. Results: Median pt age was 68 years; 52% were Asian, 43% white, and 5% Black; 19% were also Hispanic; 62% had a history of viral hepatitis. ctDNA measurements at baseline and after 1 dose of cemiplimab were available from 19 pts who completed neoadjuvant cemiplimab and underwent successful surgical resection. Pre-surgical absolute ctDNA levels decreased by >50% in 10 pts, including all with greater than 50% tumor necrosis. As of August 1, 2022; median follow-up for the adjuvant period was 23 months (interquartile range: 20-26 months). 8 pts of the 19 pts have relapsed. Pts with a >50% decrease in ctDNA had median RFS of 28 months (95% CI 10, 28), vs 17 months (95% CI 4, not evaluable [NE]) in those with ≤50% decrease in ctDNA. 17 pts had a baseline ctDNA measurement, surgical resection, and data following surgery. ctDNA detection following surgery was associated with disease relapse (Fischer’s exact test, p=0.015), shorter RFS (median 10 months, 95% CI: 4, 28) compared to ctDNA-negative pts (not reached, 95% CI 13 months, NE; hazard ratio 0.14, p=0.006), and identified molecular relapse based on ctDNA with a median lead time of 5 months before imaging relapse. 20 pts (95%) were alive at last follow-up. Interpretation: Changes in ctDNA identify early response to immunotherapy more accurately than standard modalities such as imaging, correlating closely with pathological responses and RFS. ctDNA monitoring during neoadjuvant treatment and following surgery may identify pts with early antitumor responses, improve the prediction of disease relapse or RFS, and inform additional early treatment decisions. Citation Format: Thomas U. Marron, Laura Brennan, Pauline Hamon, Maria Isabel Fiel, Stephen C. Ward, Yuan O. Zhu, Edward Kim, Alice O. Kamphorst, Pradeep Thanigaimani, Thomas S. Uldrick, Natalie Lucas, Kathy Wu, Olivia Hapanowicz, Paula King, Siyu Li, Elizabeth Miller, Nina Bhardwaj, Gavin Thurston, Israel Lowy, Sacha Gnjatic, Myron E. Schwartz, Vladimir Jankovic, Miriam Merad. Circulating tumor DNA (ctDNA) correlates closely with tumor necrosis and relapse-free survival (RFS) in hepatocellular carcinoma (HCC) patients treated with perioperative cemiplimab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2178.

267 Background: Financial toxicity (FT) adversely influences patient quality of life and is a barrier to clinical trial enrollment. Early phase clinical trials (EPTs) primarily recruit patients with advanced malignancies who have received all standard therapy regimens and may thus have high levels of FT. We sought to assess baseline FT and its association with clinicodemographic factors in patients participating in early phase clinical trials. Methods: We conducted a study to assess baseline FT in English-speaking patients (pts) with advanced metastatic solid tumors who were participating in EPTs at the Yale Cancer Center (Yale) and the Tisch Cancer Institute at Mount Sinai (Sinai). Pts were consented after EPT consent and prior to day 1 of study treatment. Pts completed a clinical and demographic questionnaire as well as the 11-item validated Comprehensive Score for Financial Toxicity (COST) FT instrument. Primary endpoints included baseline FT and association with clinicodemographic variables. Statistical analysis was performed using two-sided T-tests and Pearson correlations for numeric data and Fisher’s Exact Test for categorical data. Multivariate analysis was performed using a linear regression model. Results: 138 pts enrolled in this study, of whom 132 completed the COST instrument (Yale, N = 84; Sinai, N = 48). Median age was 62 and 49.2% were male. 71.2% patients self-identified as White and 15.2% as Black; 7.2% identified as Hispanic. 32.6% reported an annual income of < $50,000. Insurance providers included private insurers (50%), Medicare (31.8%), Medicaid (10.6%), and Medicaid with Medicare supplemental (3.8%). 56.8% reported monthly out of pocket medical expenses of $100 or more. Median FT score was 22.5 out of a maximum score of 44 (mean 21.5). FT scores ≥ 22.5 in pts were associated with age < 65 (OR = 2.229, P = 0.04), being the household money manager (OR = 2.98, P = 0.02), and being the primary wage earner (OR = 3.12, P = 0.004). FT scores < 22.5 in pts was associated with retirement (OR = 0.15, P = 3.67e-05). In multivariate analysis, retirement was associated with FT score < 22.5 (OR = 0.18, P = 0.02). There was no statistically significant difference in FT scores between Yale and Sinai pts. However, Sinai pts were more racially diverse (p = 3.05e-05), had lower household income (P = 0.01), out of pocket expenses (P = 0.01), ED visits (P = 0.0075), and dependents (P = 0.004) and were less likely to have private insurance (P = 0.004). Conclusions: Pts with advanced cancers consenting to EPTs report significant baseline FT. Our study encompasses a diverse population from two large urban academic centers. Baseline FT was higher among pts < 65 years of age, primary wage earners, and those who managed household finances independently. Retirement was a protective factor, which may be explained by the life savings often required to retire. Ongoing work will compare baseline and 2 month FT in this patient population.