TPS465 Background: Current US based guidelines for locally advanced gastric/esophageal adenocarcinoma (GEA) (LAGEA) recommend peri-operative chemo-immunotherapy for all patients with at least cT2+ or any cN+ GEA. The specific regimen and duration of peri-operative systemic treatment is standardized, rather than personalized to biologic response. Given the availability of several different classes of active agents in the treatment of GEA, the unmet need in the treatment of LAGEA is a personalized approach with real-time adaptation of the treatment regimen based on biologic response. The Northstar Response (R) is a tissue-free treatment monitoring test that achieves a limit of detection down to 0.01% tumor fraction. We hypothesize that the Northstar Response(R) ctDNA assay can closely monitor response to treatment and guide neoadjuvant treatment (NAT) regimens based on response without negatively affecting curative intent surgery or surgical complications. Methods: Our prospective single center, single arm, open label Phase IB study in clinical stage IB-III GEA will measure ctDNA at baseline, and repeated every 8 weeks. Pts are treated with standard NAT (e.g. D-FLOT). Depending on ctDNA response the same regimen will either be maintained or switched to a different NAT backbone (e.g. irinotecan based regimen). Pts will proceed to surgery after a 4-6 mo of NAT. The primary and 2ndary objectives are feasibility, and safety/efficacy, respectively. Primary endpoint: % of pts completing per protocol NAT. 2ndary endpoints: % of pts completing resection, R0 rate, 30d post-op morbidity, % ctDNA clearance after NAT and resection, safety/AEs by CTCAE v5, RFS. Key eligibility inclusion criteria include adenocarcinoma by histology, cT2+ and/or N+, age ≥18, ECOG 0-2, life expectancy >6mo, adequate organ function, surgically resectable; Exclusion criteria include known metastases, other histologies, major comorbidities. The main objective is to describe feasibility, without formal hypothesis testing, including % of pts completing per protocol treatment (95% CI). Total enrollment will be 20 pts. Enrollment began in June 2025. 4 pts started NAT. Enrollment numbers will be updated at the meeting. Clinical trial information: NCT05733689 .
Dayyani et al. (Sat,) studied this question.