On April 30, 2026 Pliant Therapeutics (Nasdaq: PLRX) reported the dosing of the first participant in the FORTIFY Phase 1b open-label indication expansion clinical trial of PLN-101095 in combination with pembrolizumab, in patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors. PLN-101095 is an oral, small molecule, dual selective inhibitor of the integrins αvβ8 and αvβ1.
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"We are pleased to announce this milestone for the FORTIFY trial and the expansion into solid tumor cohorts that we believe are supported by PLN-101095’s mechanism of action," said Bernard Coulie, M.D., Ph.D.., Chief Executive Officer of Pliant. "As a leader in integrin drug development, we look forward to exploring the full potential of this novel drug candidate."
FORTIFY – Phase 1b Clinical Trial Design
The primary objective of this trial is to evaluate the safety, tolerability, pharmacokinetics and preliminary evidence of anti-tumor activity of PLN-101095 when administered orally in combination with pembrolizumab in adult participants with advanced or metastatic solid tumors. The expansion trial is enrolling three cohorts of patients with NSCLC, clear cell renal cell carcinoma, or one of a subset of tumors with high tumor mutational burden. Patients will be treated for 14 days with PLN-101095 as monotherapy dosed at 1,000 mg twice daily, after which pembrolizumab will be added as combination therapy. Enrollment is underway with interim data expected in 2027.
PLN-101095 for the Treatment of Checkpoint Resistant Tumors
PLN-101095 is an oral, small molecule inhibitor of integrins αvβ8 and αvβ1. Activated transforming growth factor-β (TGF-β) has been shown to foster an immuno-suppressive tumor microenvironment (TME) that contributes to immune-checkpoint inhibitor (ICI) resistance and treatment failure in cancer.1 Blocking integrins αvβ8 and αvβ1 has been shown to prevent the activation of TGF-β and is expected to stimulate immune activation by increasing immune cell infiltration into the tumor microenvironment.2,3 PLN-101095 is currently being evaluated in Phase 1a/1b open-label, dose-escalation and indication expansion trial (NCT 06270706) to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of PLN-101095 in combination with pembrolizumab, in patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors. PLN-101095 in combination with an anti-PD-1 monoclonal antibody (mAb) elicited a dose-dependent reduction in tumor volume and increased CD8+ T cell tumor infiltration in the tumor microenvironment compared with anti-PD-1 mAb therapy alone.4 In preclinical studies, PLN-101095 demonstrated monotherapy activity in reduction of tumor volume and increased cluster of differentiation (CD)8+ T cell infiltration.
(Press release, Pliant Therapeutics, APR 30, 2026, View Source [SID1234664996])