45P - Durvalumab (D) plus gemcitabine-based (gem-based) chemotherapy as first-line therapy for Chinese patients (pts) with advanced biliary tract cancers (aBTC): A phase IIIb, single arm, open-label, multi-center study (TopDouble)

Background

Following the TOPAZ-1 study, D + gemcitabine and cisplatin (GC) emerged as a standard therapy for aBTC. However, gem-based chemotherapy other than GC is also commonly used in Chinese clinical practice. Our study aimed to evaluate the safety and efficacy of D combined with other gem-based chemotherapy in aBTC and D plus GC in aBTC with ECOG PS 2. Here, we present the interim analysis (IA) outcomes.

Methods

Pts with aBTC will be treated with D plus an investigator-selected gem-based chemotherapy [(gemcitabine + oxaliplatin (GEMOX), gemcitabine + S1 (GS), GC (only for ECOG PS 2 pts)]. The primary endpoint is incidence of grade 3 or 4 possibly related adverse event (G3/4 PRAE) within 6 months after the initiation of combined therapy. Secondary endpoints include overall survival, objective response rate, disease control rate. Exploratory endpoints will include genomic analysis of formalin-fixed paraffin-embedded tumor tissue using the Geneseeq Prime® panel to investigate China-specific BTC genetic alterations, mechanisms of resistance to treatment and identify putative biomarkers of prognosis.

Results

At data cutoff Jan 20, 2024, 112 pts were enrolled in the study (GEMOX, n=45; GS, n=49; GC, n=18). Median follow-up was 3.02m (GEMOX: 2.86m, GS: 3.75m, GC: 1.66m). G3/4 PRAE within 6 months after the initiation of combined therapy occurred in 52 (46.4%) pts, which is 40.0%, 57.1%, and 33.3% in the GEMOX, GS, and GC groups, respectively. The most common G3/4 PRAE were neutrophil count decreased (15.2%), white blood cell count decreased (11.6%) and anaemia (10.7%). Serious adverse event (SAE) occurred in 27.7% pts. Immune-mediate adverse events (imAEs) were reported in 22.3% of pts. A total of 102 pts were included in exploratory analysis, TP53 (53.9%), KRAS (24.5%), ARID1A (19.6%), CDKN2A (18.6%), TERT (18.6%), SMAD4 (15.7%) were the most frequently altered genes.

Conclusions

The IA analysis showed D plus gem-based chemotherapy was consistent with the safety profiles of the TOPAZ-1 study. No new safety signals emerged. Efficacy data and updated exploratory data will be presented in the future.

Clinical trial identification

NCT05924880.

Editorial acknowledgement

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

All authors have declared no conflicts of interest.