Pliant Therapeutics releases interim data from Phase I trial of PLN-101095

Pliant Therapeutics has disclosed preliminary findings from its ongoing Phase I dose-escalation study of PLN-101095, administered alongside pembrolizumab in patients with solid tumors. The investigational therapy targets individuals with advanced or metastatic tumors that have not responded to immune checkpoint inhibitors (ICIs).

PLN-101095 is an oral, dual-selective small molecule that inhibits alpha-v beta-8 (v8) and v1 integrins. It represents the fourth clinical-stage candidate emerging from Pliants integrin-focused drug development platform.

In the trial, combining PLN-101095 with pembrolizumab demonstrated measurable anti-tumor activity in patients with ICI-refractory solid tumors. Among ten participants in the three highest dose cohorts, four responses were recorded: three partial responses (two confirmed, one unconfirmed) and one confirmed complete response. Positive outcomes were observed in patients with head and neck squamous cell carcinoma, cholangiocarcinoma, non-small cell lung cancer, and melanoma.

As of November 30, 2025, patients had been on treatment for a median duration of 15 months, with 60% of ICI-refractory patients achieving either tumor reduction or stable disease. Responding patients also exhibited substantial elevations in plasma interferon gamma (IFN-), ranging from fourfold to 13-fold compared with baseline following a 14-day PLN-101095 monotherapy run-in.

The treatment was generally well tolerated, with only two discontinuations due to adverse events, and displayed a dose-dependent pharmacokinetic profile. The study enrolled 16 participants with nine different tumor types across five dosing groups. PLN-101095 monotherapy doses included 250mg twice daily (BID) for one patient, 500mg BID for two patients, 1,000mg BID for six patients, 1,000mg three times daily for four patients, and 2,000mg BID for three patients. After monotherapy, pembrolizumab was administered at 200mg intravenously every three weeks.

Pliant plans to initiate a Phase Ib expansion study next year to evaluate PLN-101095 in non-small cell lung cancer and additional tumor types. CEO Bernard Coulie highlighted the encouraging results, noting that the trial exceeded expectations for response rates in difficult-to-treat ICI-refractory tumors. He emphasized that the IFN- biomarker correlation supports the drugs mechanism of action and reinforces the potential for PLN-101095 to offer new treatment options.

Sources:

• Pliant Therapeutics reports interim PLN-101095 Phase I trial data