Dr Timothy Yap speaks to ecancer about the first-in-human results of PLN-101095, a novel oral dual integrin inhibitor targeting αvβ8 and αvβ1, designed to block TGF-β activation and overcome immunotherapy resistance.

In patients with advanced solid tumours refractory to prior immune checkpoint inhibitors, the combination of PLN-101095 and pembrolizumab demonstrated encouraging and durable antitumour activity, including complete and partial responses across multiple tumour types.

Notably, responses were observed in heavily pretreated, ICI-resistant populations.

Dr Yap says that the treatment was generally well tolerated, with mostly low-grade adverse events and limited dose-limiting toxicity. Pharmacodynamic analyses showed early immune activation, with increases in interferon gamma and other immune markers correlating with clinical response.

He highlights that these findings support PLN-101095 as a promising strategy to reverse immune resistance, with ongoing expansion studies further evaluating its role in ICI-refractory cancers.