PRT3789-02 - A Phase 2, Safety and Efficacy Study of PRT3789 in Combination with Pembrolizumab in Patients with Advanced or Metastatic Solid Tumors with a SMARCA4 Mutation

A drug that targets a specific genetic mutation is being tested in combination with an existing immunotherapy to treat advanced oesophageal and lung cancers. Around 10% of non-small cell lung cancers and a subset of oesophageal cancers carry a mutation in the SMARCA4 gene, which helps regulate how DNA is packaged inside cells. When this gene stops working, tumours often become resistant to standard treatments, including PD-L1 inhibitors. This trial is testing whether adding PRT3789—a drug that blocks a protein called PRMT5, which these cancer cells rely on to survive—can restore or enhance the effectiveness of pembrolizumab, a widely used immunotherapy. If the combination proves safe and shows signs of shrinking tumours, it could offer a new treatment option for patients whose cancers have stopped responding to existing therapies. The study first tests the drug pairing in a small group of patients with any solid tumour, then expands to roughly 40 patients specifically with SMARCA4-mutant oesophageal or non-small cell lung cancer. Success would mean that a genetic test could identify which patients might benefit from this targeted approach, moving beyond one-size-fits-all chemotherapy.