Bexotegrast

Antitumor activity observed with confirmed partial responses in 50% of patients at highest dose tested to date, across multiple tumor types PLN-101095 was generally well tolerated across all doses March 17, 2025 -- Pliant Therapeutics, Inc. (Nasdaq: PLRX) today announced data from the first three of five potential cohorts of its ongoing Phase 1 dose escalation clinical trial evaluating PLN-101095, an integrin αvβ8 and αvβ1 inhibitor, in combination with pembrolizumab, in patients with immune checkpoint inhibitor (ICI) -refractory advanced or metastatic solid tumors. Interim results demonstrated PLN-101095 anti-tumor activity in combination with pembrolizumab, with three partial responses observed in cohort three at the 1000 mg administered orally twice daily (BID) dose, representing a 50% objective response rate (ORR) at the highest dose tested to date. PLN-101095 was generally well tolerated across all doses tested. Nine patients with six different tumor types were enrolled in cohorts one through three of the trial. Patients were treated for 14 days with PLN-101095 at doses of 250 mg, 500 mg or 1000 mg administered orally BID, followed by treatment with a combination of PLN-101095 and pembrolizumab at 200 mg administered intravenously every three weeks (Q3W). Scans were conducted at baseline, Day 14, Week 10, and every 8 weeks thereafter. The Company reported the following initial observations from the trial: Across all doses tested, PLN-101095 was generally well tolerated Of the six patients treated at the 1000 mg BID dose of PLN-101095, three (50%) confirmed partial responses were observed. All three patients remain on treatment. Non-Small Cell Lung Cancer (NSCLC): Confirmed partial response with a 74% reduction in tumor size at Week 18; initial partial response was observed at Week 10 Cholangiocarcinoma: Confirmed partial response with a 48% reduction in tumor size at Week 42; initial partial response was observed at Week 34 Melanoma: Confirmed partial response with a 42% reduction in tumor size at Week 27; initial partial response was observed at Week 18 “We are encouraged by these early responses given the refractory nature of the patient population enrolled in this trial,” said Éric Lefebvre, M.D., Chief Medical Officer of Pliant. “We look forward to sharing the final results from this trial in the future.” The Phase 1 trial of PLN-101095 is currently enrolling the fourth of five potential cohorts. The fourth cohort is evaluating PLN-101095 at 1000 mg, three times daily (TID). PLN-101095 is an oral small molecule inhibitor of integrins αvβ8 and αvβ1. It is currently being evaluated in an ongoing first-in human Phase 1 dose-escalation trial. The open-label trial (NCT06270706) is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of PLN-101095 alone and in combination with the immunotherapy pembrolizumab. Activated transforming growth factor-β (TGF-β) has 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 shown to prevent the activation of TGF-β and is expected stimulate immune activation by increasing immune cell infiltration into the tumor microenvironment.2,3 In preclinical studies, PLN-101095 demonstrated monotherapy activity in reduction of tumor volume and increased cluster of differentiation (CD)8+ T cell infiltration. In addition, 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 Pliant Therapeutics is a late-stage biopharmaceutical company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases. Pliant's lead product candidate, bexotegrast (PLN-74809), is an oral, small molecule, dual selective inhibitor of αvβ8and αvβ1 integrins that is in development in the lead indication for the treatment of idiopathic pulmonary fibrosis, or IPF. Bexotegrast has received Fast Track Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and Orphan Drug Designation from the European Medicines Agency in IPF. Pliant is conducting a Phase 1 study for PLN-101095, a small molecule, dual-selective inhibitor of αvβ8 and αvβ1 integrins, that is being developed for the treatment of solid tumors. In addition, Pliant has received regulatory clearance for the conduct of a Phase 1 study of PLN-101325, a monoclonal antibody agonist of integrin α7β1 targeting muscular dystrophies. 1 Pickup M. et al. Nat Rev Cancer. 2013 Nov;13(11):788-99. 2 Takasaka N. et al. JCI Insight. 2018 Oct 18;3(20). 3 Reed NI. et al. Sci Transl Med. 2015 May 20;7(288):288ra79. 4 Kothari V, et al. J Immunother Cancer 2022;10(Suppl 2): A1403 abstract 1352 (SITC 2022) The content above comes from the network. if any infringement, please contact us to modify.