Shubham Pant

Camupepimut (ELI-002 7P) drives mutated KRAS (mKRAS)-specific T cell responses that correlated with disease-free survival (DFS) and overall survival (OS) in patients with mKRAS pancreatic adenocarcinoma (PDAC) in the phase 1 AMPLIFY-201 trial. In the phase 2 AMPLIFY-7P trial, patients with stage I-III KRAS-mutated PDAC without recurrence within 6 months of standard therapy were randomized 2:1 to camupepimut (n = 96) or standard-of-care/observation (n = 48). Stratification balanced nodal status. The primary DFS endpoint was not met (median 23.8 versus 21.2 months; HR 0.85, P = 0.5329). However, prespecified and exploratory analyses were informative. A numerical DFS advantage at 6 months of 14.0% (75.7% versus 61.7%; HR 0.55, P = 0.0557) corresponded to camupepimut dosing. Post hoc multivariate Cox regression analysis of DFS indicated an improved outcome for camupepimut (adjusted HR 0.47, P = 0.0086), a worse outcome for stage III disease (adjusted HR 2.29, P = 0.0127), an elevated baseline CA19-9 (adjusted HR 3.16, P < 0.0001) and baseline circulating tumor DNA (ctDNA) positivity (adjusted HR 5.99, P < 0.0001). Prespecified subgroup analyses addressing prognostic and predictive factors suggested DFS benefit for camupepimut (ctDNA negative: HR 0.51, P = 0.0280; no prior radiation: HR 0.59, P = 0.0221). Exploratory analysis demonstrated that ex vivo mKRAS-specific T cell responses were robust (98.9%, 89/90) and associated with antigen spreading (86.7%, 13/15). In camupepimut-treated patients, mKRAS-specific T cell response >9.17-fold over baseline (82.2%, 74/90) correlated with improved DFS (HR 0.22, P < 0.0001), with the median DFS not reached versus 6.08 months for above and below 9.17-fold, respectively. Camupepimut safety was similar to observation, with grade ≥3 adverse events in 10.4% (10/96) versus 14.6% (7/48), and few serious AEs (6.3%, 6/96 versus 8.3%, 4/48; reflecting progression/surgical complication). These efficacy and immunogenicity signals will inform a refined strategy for a confirmatory phase 3 trial. ClinicalTrials.gov identifier: NCT05726864.

Survival outcomes in ASQ versus PDAC

Pathologic and molecular features

Neoadjuvant chemotherapy regimens in spatial transcriptomics cohort

Full statistics for pathway enrichment analysis of ASQ versus PDAC

Tissue sampling sites in FoundationOne cohort

Full statistics for differential gene expression analysis of ASQ versus PDAC

Full statistics for differential gene expression analysis of squamous versus glandular regions in ASQ

Full statistics for pathway enrichment analysis of squamous versus glandular regions in ASQ

Cholangiocarcinoma (CCA) includes a heterogeneous group of malignancies arising from the biliary epithelium, anatomically classified into intrahepatic, perihilar, and distal disease, with subtype-specific molecular features and treatment implications. Intrahepatic CCA is further subclassified into small- and large-duct variants. Most patients present with advanced, unresectable disease, and 5-year survival rates remain poor. For over a decade, gemcitabine-cisplatin (Gem-Cis) combination chemotherapy was the only established first-line standard of care. More recently, the addition of immune checkpoint inhibitors (IO), durvalumab and pembrolizumab, to Gem-Cis in the TOPAZ-1 and KEYNOTE-966 trials, respectively, improved overall survival, establishing chemoimmunotherapy as the new first-line therapy. Given the high prevalence of actionable alterations in CCA, comprehensive molecular profiling has become indispensable for second-line treatment selection and front-line clinical trial eligibility. FGFR2 fusions, IDH1 mutations, and HER2 amplification are among the most relevant, with several targeted agents now available in the second-line setting. Despite this progress, most patients exhaust treatment options within the first year, highlighting the need for further therapeutic advances. Emerging strategies include novel targeted agents, antibody-drug conjugates, locoregional approaches for liver-limited disease, and circulating tumor DNA monitoring for real-time treatment adaptation. The immunosuppressive tumor microenvironment and the absence of reliable predictive biomarkers for IO response remain key challenges that ongoing research aims to address. This review summarizes current evidence for the management of advanced CCA, focusing on molecular profiling, treatment sequencing, and emerging therapies.