Pliant Therapeutics Announces Presentation of PLN-101095 Preclinical and Clinical Data at the 2026 Annual Meeting of the Society for Immunotherapy of Cancer

(NASDAQ:PLRX) Pliant Therapeutics, Inc. announced the presentation of preclinical proof-of-concept data and new clinical biomarker analyses related to PLN-101095 at the 41st Annual Meeting of the Society for Immunotherapy of Cancer (SITC). Nika Rajabian, Ph.D., Postdoctoral Fellow from the National Cancer Institute, presented data showing that blocking integrins αvβ8 and αvβ1 in combination with anti-PD-1 reduced TGF-β signaling, modulated fibroblastic cell populations in the tumor microenvironment, and increased infiltration and activation of cytotoxic CD8+ T cells. This combination resulted in improved anti-tumor activity and survival in preclinical models. The data provide rationale for an ongoing, first-in-human phase I clinical trial (NCT06270706) of PLN-101095 in combination with pembrolizumab in solid cancers. The work was conducted under a collaboration agreement between the National Cancer Institute and Pliant Therapeutics. Martin L. Decaris, Ph.D., Vice President of Translational Sciences at Pliant Therapeutics, presented new biomarker data from the Phase 1 trial of PLN-101095, showing that early induction of immune activation biomarkers during PLN-101095 monotherapy was associated with subsequent clinical response following pembrolizumab initiation. These findings support the hypothesis that TGF-β pathway inhibition promotes immune activation, T-cell recruitment into the tumor microenvironment, and enhanced cytotoxic effector function. PLN-101095 is currently being evaluated in a Phase 1a/1b open-label, dose-escalation and indication expansion trial (NCT06270706) to assess safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity when administered orally in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors. The Phase 1b portion of the FORTIFY trial is enrolling three cohorts: patients with non-small cell lung cancer (NSCLC), tumors with high tumor mutational burden, or clear cell renal cell carcinoma. Patients are treated for 14 days with PLN-101095 dosed at 1,000 mg twice daily as monotherapy, after which pembrolizumab is added as combination therapy. Pliant’s lead program is PLN-101095, an oral, small molecule, dual-selective inhibitor of αvβ8 and αvβ1 integrins, being developed for the treatment of ICI-refractory advanced or metastatic solid tumors. Pliant’s preclinical research also focuses on tissue-specific delivery and internalization of drug payloads using integrin receptor-binding molecules, with programs targeting delivery of siRNAs to skeletal muscle cells, adipocytes, and renal cells.

Pliant Therapeutics Announces First Patient Dosed in FORTIFY, the Phase 1b Indication Expansion Trial Evaluating PLN-101095 in Patients with ICI-Refractory Solid Tumors

Pliant Therapeutics (NASDAQ:PLRX) announced the dosing of the first participant in the FORTIFY Phase 1b open-label indication expansion clinical trial of PLN-101095 in combination with pembrolizumab for patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors. The trial is enrolling three cohorts of patients with NSCLC, clear cell renal cell carcinoma, or tumors with high tumor mutational burden. Patients will receive PLN-101095 as monotherapy dosed at 1,000 mg twice daily for 14 days before adding pembrolizumab. Enrollment is underway with interim data expected in 2027. This milestone marks an important step in the development of PLN-101095 for treatment-resistant cancers.