PLN-101095 Phase 1 data show interferon-gamma increases in responders

Pliant reported updated Phase 1 data showing that responders to PLN-101095 plus pembrolizumab had large increases in plasma interferon-gamma and elevated PD-L1; the drug was generally well tolerated with mainly mild rash and one Grade 3 treatment-related adverse event.

Pliant Therapeutics presented updated Phase 1 data for PLN-101095 given with pembrolizumab at the AACR 2026 Clinical Trials Mini Symposium. The trial enrolled patients with immune checkpoint inhibitor–refractory advanced or metastatic solid tumors. Reported data show that patients who responded had notable changes in immune biomarkers after a 14-day monotherapy run-in with PLN-101095. The company reported generally tolerable safety across doses, with rash cited as the most common treatment-related event. Key findings: - The oral presentation was delivered at the AACR 2026 Clinical Trials Mini Symposium. - All responding patients showed large increases in plasma interferon-gamma following a 14-day PLN-101095 monotherapy run-in. - At Week 10, all responders maintained more than a two-fold increase in interferon-gamma, while non-responders did not show meaningful increases. - Responding patients also showed elevated plasma PD-L1, which the report notes can be induced by interferon-gamma and is associated with improved immune checkpoint inhibitor responses. - The company described interferon-gamma increases as a potential biomarker of TGF-beta inhibition and an early indicator of PLN-101095 anti-tumor activity, and said it will study this biomarker further in Phase 1b expansion cohorts. - Safety was described as generally well tolerated across evaluated doses; rash was the most common treatment-related adverse event (all Grade 1–2 and mostly occurring within two days of the initial pembrolizumab dose), and one Grade 3 treatment-related adverse event was observed. Summary: The update links interferon-gamma and PD-L1 increases with responses in this Phase 1 setting and reports a tolerable safety profile with mostly mild rash. Pliant plans to study interferon-gamma as a biomarker in expansion cohorts of the Phase 1b trial. The broader clinical implications and durability of responses are undetermined at this time.