62A Phase 1/11 Study ofCDX-1140, CAPOX and Pembrolizumab in Second-line Biliary Tract Cancer
Tim F Greten, Donna Mabry-Hrones, David E Kleiner, Bradford J Wood, Bernadette ReddAbstract
Background
Advanced biliary tract carcinoma (BTC) carries a poor prognosis, and effective treatment options are limited in the second-line setting. While chemotherapy combined with PD-I blockade has demonstrated modest clinical activity, primary and acquired resistance remain major challenges. Preclinical studies indicate that CD40-mediated activation of antigen-presenting cells can enhance antitumor immunity and improve response to immune checkpoint inhibition, particularly when combined with chemotherapy.
Methods
This is an ongoing Phase I/II, single-arm, open-label study evaluating the safety and efficacy of the CD40 agonist antibody CDX-1140 in combination with capecitabine and oxaliplatin (CAPOX) and pembrolizumab in patients with advanced BTC who have progressed following prior systemic therapy. The Phase I portion uses a dose-escalation design to determine the recommended Phase II dose (RP2D) of CDX-1140 in combination with CAPOX and pembrolizumab. Phase II evaluates clinical efficacy at the RP2D. The primary Phase II endpoints are 6-month progression-free survival (PFS) and overall response rate (ORR) per RECIST vl.l. Secondary objectives include safety and overall survival. Exploratory endpoints include immune profiling of blood and tumor tissue, assessment of PD-Ll expression, cytokine analyses, multiplex immunohistochemistry, and genomic and transcriptomic analyses including ctDNA.
Status
The protocol plans to enroll up to 60 participants across two U.S. sites, with efficacy assessed by 6-month PFS and ORR. The phase I portion is completed, and we are currently enrolling on the phase II portion of the trial. We will present preliminary clinical results.
Trial Registration
NCT05849480