Liu, Jingxia

TPS3648 Background: Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes tryptophan along the kynurenine pathway and is recognized as a potent suppressor of tumor reactive immunity. Epacadostat is an orally active, potent and selective inhibitor of IDO1. In preclinical studies, IDO1 was found to promote resistance to radiation in rectal cancer, irrespective of microsatellite instability (MSI) status. IDO1 inhibition with epacadostat improved tumor radiosensitivity by relieving immune suppression and augmenting radiation-induced apoptosis while protecting the normal intestine from radiation damage. In a phase 1 trial, 17 patients were enrolled from 4/2019 to 8/2023. Epacadostat in combination with short-course radiation therapy (SCRT) and CAPOX was well-tolerated and the recommended phase 2 dose (RP2D) of epacadostat was determined to be 400 mg BID. An NCI supported Phase 2 trial is ongoing to further evaluate the promising disease responses reported in the dose escalation phase. Methods: This phase 2 multicenter, open-label trial includes treatment and biomarker cohorts. In the treatment cohort, epacadostat at 400 mg BID will be administered concurrently with SCRT followed by epacadostat monotherapy until 1 day prior to neoadjuvant chemotherapy, followed by standard-of-care (SOC) neoadjuvant chemotherapy and, ultimately, surgical resection or non-operative management (NOM). Biomarker cohort enrollment will commence at completion of treatment cohort accrual. Enrolled patients will be treated with SOC SCRT followed by SOC neoadjuvant chemotherapy and surgical resection or NOM. Eligible patients must be a treatment-naïve, newly diagnosed, pathologically confirmed, locally advanced rectal cancer (defined by 8 th edition AJCC stage 2 or 3, or stage 1 not eligible for sphincter-sparing surgery) with plans to proceed with neoadjuvant SCRT and chemotherapy. The primary endpoint is the neoadjuvant rectal (NAR) score. Secondary endpoints are pathologic complete response (pCR) rate, complete clinical response (cCR) rate and progression-free survival (PFS). Exploratory endpoints are pharmacodynamics, PDX and organoid generation, identification of molecular predictors of response and resistance, correlation of radiographic and pathologic response and effect of treatment on patient quality of life. We aim to enroll 27 patients in the treatment cohort and 10 in the biomarker cohort. Clinical Trial Registration: NCT03516708 .

801 Background: SBA is a rare, poorly understood gastrointestinal malignancy. Adenocarcinomas are often grouped with other small bowel cancer histologies in epidemiologic and outcomes reports, which limits the ability to detect SBA-specific trends. Recent studies in European populations show increasing SBA incidence, but there are limited published data in American cohorts. Identifying trends in SBA can improve understanding of the population most at risk for developing SBA. This study describes U.S. trends in SBA incidence and outcomes from 2000 to 2019. Methods: Using the 2022 SEER research-limited dataset, we identified SBA cases and measured the incidence change from 2000-2019. We built linear regression models to evaluate changes in annual incidence by groups, including sex, race, and age of diagnosis, separately. We then compared the overall incidence and trends between subgroups. We investigated overall survival (OS) through the SEER research case listings for SBA patients diagnosed during the study period. Results: An average of 0.67 cases/100,000 SBA cases were reported annually from 2000-2019, with a median diagnosis age of 69 years. SBA incidence has increased annually by 0.3% per year from 2000-2019 (p=0.05). From 2000-2019, men were at a higher risk for SBA compared to women (p=0.02). In men, SBA cases increased at a rate of 0.004 cases/100,000/year from 2000-2019 (p=0.01) and a nonsignificant decrease in women of 0.00012 cases/100,000/year. There were no statistically significant differences in incidence or the change in incidence of SBA by race. The age-adjusted incidence was significantly higher each year between 2000 and 2019 in the > 70 cohort compared to the <70 cohort (p=0.02). Cases of SBA increased at a rate of 0.02 cases/100,000/year in adults >70 years (p=0.02). There were no differences in incidence rates in patients <70 years. There was no significant difference in OS for patients diagnosed with SBA in 2000, 2005, 2010, 2015, and 2019 (p=0.21). Conclusions: The overall annual incidence of SBA is increasing in the U.S. population. The most significant rate increases are in men and adults older than 70. In the SEER population, trends in SBA contrast with the recent rise of colorectal cancer in the young adult population, highlighting the unique nature of SBA compared to other gastrointestinal malignancies. Additionally, survival outcomes in patients diagnosed with SBA have remained stable over the past 20 years, while other malignancies have shown improvement in the same period. The small cohort size and the lack of a universal U.S. cancer registry limited this evaluation. Improved reporting of SBA cases and further research to identify risk factors are urgently needed to reduce the growing impact of SBA.