DNA Damage Repair & PARP-Immunotherapy

Combining DNA-damage-repair targeting with immunotherapy in BRCA/PALB2-mutated and HRD pancreatic cancer.

Overview

Roughly one in six pancreatic cancers harbour defects in DNA damage repair. We exploit those defects therapeutically by combining PARP inhibition with immune checkpoint blockade in biomarker-selected patients.

The POLAR trial

Our investigator-initiated phase 2 POLAR trial demonstrated that maintenance pembrolizumab + olaparib yields a median overall survival of 28 months and a 3-year OS rate of 44% in BRCA/PALB2-mutated metastatic pancreatic cancer.

These results, published in Nature Medicine (2026), establish a chemotherapy-free maintenance strategy for a genetically defined subgroup and link ctDNA dynamics and neoantigen landscape to durable benefit.

Biomarkers

We use HRD status, mutational signatures (COSMIC signature 3, LST, LOH, TAI), and ctDNA response to identify the patients most likely to benefit and to monitor response in real time.