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PLN-101095 in combination with pembrolizumab led to responses in patients with ICI-refractory advanced solid tumors.
PLN-101095, an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1, in combination with pembrolizumab (Keytruda) demonstrated antitumor activity for the treatment of patients with immune checkpoint inhibitor (ICI)–refractory advanced or metastatic solid tumors, according to interim data from a phase 1 study (NCT06270706).1
Findings from the dose-escalation trial demonstrated that among patients treated at the 1,000-mg dose level of PLN-101095 (n = 6), 3 achieved a clinical response.2 Another patient experienced a clinical response at the 2,000-mg dose level (n = 3). Among the 10 patients treated across the 3 highest dose levels with ICI secondary refractory disease, responses consisted of 1 confirmed complete response and 3 partial responses (2 confirmed, 1 unconfirmed). Responses were reported in patients with cholangiocarcinoma, melanoma, head and neck squamous cell carcinoma, and non–small cell lung cancer (NSCLC).1
“These data surpassed our expectations given the number of clinical responses observed with PLN-101095 in difficult-to-treat ICI refractory tumors in similar phase 1 trials,” Bernard Coulie, MD, PhD, president and chief executive officer of Pliant Therapeutics, stated in a news release. “The growing validation of PLN-101095’s mechanism of action, including the supportive IFN-γ biomarker correlation, gives us confidence in PLN-101095’s development. We believe PLN-101095 has the potential to create new treatment options for patients in need and deliver significant value for investors.”
The multicenter, dose-escalation/expansion, consecutive-cohort, open-label study enrolled adult patients with advanced/metastatic solid tumors for which pembrolizumab is indicated who experienced disease progression or relapse after at least 3 months from the initiation of pembrolizumab.3 Patients also needed to have at least 1 measurable lesion per RECIST 1.1 criteria, an estimated life expectancy of at least 3 months, and no effective therapeutic options available in order to be eligible for enrollment.
Patients received PLN-101095 at 250 mg (n = 1), 500 mg (n = 2), 1,000 mg (n = 6), or 2,000 mg (n = 3) twice daily, as well as at 1,000 mg 3 times daily (n = 4).2 Over days 1 through 15, PLN-101095 was given as monotherapy; the agent was given in combination with pembrolizumab starting at day 15. The dose-limiting toxicity (DLT) window started at day 35 and tumor response was assessed at week 10 and every 8 weeks thereafter.
The primary end points were safety and the rate of DLTs.3 Secondary end points included disease control rate (DCR), objective response rate, and pharmacokinetic measures.
At the November 30, 2025, data cutoff, the median time on treatment among responders was 15 months.2 The DCR was 60%.
In terms of safety, the most common any-grade treatment-emergent adverse effects (TEAEs) in the total population (n = 16) included rash (50%), anemia (19%), and diarrhea (19%). Serious TEAEs were reported in 31% of patients.
“These first-in-human data suggest that this novel approach of selectively targeting αvβ8 and αvβ1 may hold promise for treating patients with advanced solid tumors resistant to checkpoint inhibitors,” Manish R. Sharma, MD, the codirector of Clinical Research at START Midwest and a medical oncologist in Grand Rapids, Michigan, added in the news release.1 “These data support the further clinical investigation of this novel mechanism of action to meet the high unmet medical needs in anti–PD-1 resistant tumors.”
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