Memorial Sloan Kettering Cancer Center
Screening · POLQ · Antigen · Repair · KRAS
A translational pancreatic cancer research laboratory developing precision therapeutics — from bench to bedside — in Manhattan, New York.
Five interconnected pillars driving translational breakthroughs in pancreatic ductal adenocarcinoma (PDAC).
Genetic and small-molecule screens — including CRISPR-based functional genomics — to find combination strategies, resistance mechanisms, and novel targets in PDAC.
Polymerase theta (POLQ) and error-prone end-joining as a source of synthetic lethal vulnerabilities in HRD-deficient tumors.
Pipelines for neoantigen discovery and biologic modalities targeting tumor-specific epitopes.
Combining DNA-damage-repair targeting with immunotherapy in BRCA/PALB2-mutated and HRD pancreatic cancer.
Targeting KRAS G12D — the most common variant in PDAC — with first-in-class degraders and RAS(ON) inhibitors.
First-in-human phase 1 study of setidegrasib (ASP3082), a first-in-class KRAS G12D targeted protein degrader. Among 21 patients with metastatic PDAC receiving the 600 mg dose, 24% achieved objective response. In NSCLC (n=45), ORR was 36% with median PFS of 8.3 months.
Phase 2 POLAR trial evaluating maintenance pembrolizumab + olaparib in biomarker-stratified metastatic PC. In cohort A (BRCA1/2, PALB2; n=33): median PFS 8.3 months, median OS 28 months, 3-year OS rate 44%. ctDNA response and enrichment of frameshift indel neoantigens were associated with durable clinical benefit.
Phase 1–2 study of daraxonrasib (RMC-6236), an oral RAS(ON) multiselective inhibitor targeting GTP-bound mutant and wild-type RAS, in 168 patients with previously treated RAS-mutated PDAC. Among 26 patients with RAS G12 mutations receiving 300 mg in second line: ORR 35%, median duration of response 8.2 months, mPFS 8.5 months, mOS 13.1 months. Grade ≥3 treatment-related adverse events in 30%.
Named clinical trials and translational efforts advancing precision therapeutics in pancreatic cancer.
Maintenance pembrolizumab + olaparib in HRD metastatic pancreatic cancer
Investigator-initiated phase 2 trial of maintenance pembrolizumab + olaparib in biomarker-stratified metastatic pancreatic cancer.
First-in-human KRAS G12D targeted protein degrader
First-in-human phase 1 trial of setidegrasib, a first-in-class KRAS G12D targeted protein degrader, in advanced PDAC and NSCLC.
Oral RAS(ON) multiselective inhibitor
Phase 1–2 study of daraxonrasib, an oral RAS(ON) multiselective inhibitor, in previously treated RAS-mutated pancreatic cancer; phase 3 RASolute 302 reported in 2026.
Personalized mRNA vaccines targeting tumor neoantigens
Personalized RNA neoantigen vaccine program priming durable, long-lived T-cell responses in pancreatic cancer.
