PLN-101095 / Pliant Therapeutics - LARVOL DELTA

Trial in Progress: Part 2 Cohort Expansion of a Phase I Study of PLN-101095, a Dual αvβ8/αvβ1 Integrin Inhibitor, in Combination With Pembrolizumab in Immune Checkpoint Inhibitor–Refractory Advanced Solid Tumours (ESMO 2026) - No abstract available

Checkpoint inhibition • Combination therapy • Metastases • P1 data • Oncology • Solid Tumor

First-in-human phase I study of PLN-101095, a first-in-class dual αvβ8/αvβ1integrin inhibitor, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors refractory to immune checkpoint inhibitors (ICI) (AACR 2026) - P1 | "PLN-101095 and pembrolizumab had durable antitumor activity in heavily pretreated ICI-secondary resistant tumors. Early systemic induction of IFN-γ emerged as a potential PD marker associated with clinical response and warrants further investigation. Based on these findings PLN-101095 is advancing to Part 1b, evaluating tumor-specific expansion cohorts in ICI-resistant populations."

Checkpoint inhibition • Clinical • Combination therapy • First-in-human • IO biomarker • Metastases • Monotherapy • P1 data • Biliary Cancer • Cholangiocarcinoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CXCL9 • GZMB • IFNG • PD-L1 • TGFB1

Pliant Therapeutics Receives FDA Fast Track Designation for PLN-101095 in Combination with Pembrolizumab for the Treatment of ICI-Refractory Solid Tumors (The Manila Times) - "PLN-101095 is currently being evaluated in the Phase 1a/1b FORTIFY trial (NCT06270706) with data expected in 2027....PLN-101095 is being investigated in FORTIFY, a Phase 1b indication expansion trial enrolling patients with NSCLC, tumors with high tumor mutational burden or clear cell renal cell carcinoma."

Fast track • P1 data • Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer • Solid Tumor

Enrollment continues in FORTIFY, a Phase 1b indication expansion trial (GlobeNewswire) - "FORTIFY will enroll up to 102 patients across three cohorts including non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC) and tumors with high tumor mutational burden. 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. Enrollment remains strong, progressing ahead of schedule. Interim data is expected in 2027."

Enrollment status • P1 data • Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer

Cohort expansion of a phase I study of PLN-101095, a first-in-class dual αvβ8/αvβ1 integrin inhibitor, in combination with pembrolizumab in patients with advanced solid tumors refractory to immune checkpoint inhibitors (ICI). (ASCO 2026) - P1 | "Planned exploratory biomarkers analyses include characterization of integrin expression, TGF-β and immune-related gene expression, and tumor microenvironment (TME) in tumor biopsies. Plasma cytokine profiling and circulating tumor DNA (ctDNA) will also be examined."

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TGFB1 • TMB

Pliant Therapeutics Announces Upcoming Presentation at the 2026 American Society of Clinical Oncology Annual Meeting (GlobeNewswire) - "Pliant is currently enrolling patients in FORTIFY, a Phase 1b open-label, indication expansion trial enrolling three cohorts of patients with non-small cell lung cancer (NSCLC), tumors with high tumor mutational burden or clear cell renal cell carcinoma."

Trial status • Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer

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

P1 data • Trial status • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer

PLN-101095-ONC-101: A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Pliant Therapeutics, Inc. | N=77 ➔ 124 | Trial completion date: Dec 2025 ➔ Jun 2030 | Trial primary completion date: Jun 2025 ➔ Jun 2030

Checkpoint inhibition • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Selective targeting of integrins αVβ8 and αVβ1 within the dynamic ecosystem of pancreatic cancer to improve the overall anti-tumor response (AACR 2024) - "Finally, utilizing patient-derived models of metastatic PDA revealed that both PLN-104 and PLN-101095 significantly blocked tumour growth, improved the response to SoC chemotherapy Gemcitabine/Abraxane, and reduced metastatic spread to distant sites. In conclusion, these data provide scientific rationale for the design of future PLN-101095 and SoC chemotherapy as well as immunotherapy combinations in pancreatic cancer, with Phase I first-in-human oncology studies with PLN-101095 plus ICB already underway."

First-in-human • IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • KRAS • PDX1 • TGFB1

PLN-101095 Phase 1b Indication Expansion Trial (The Manila Times) - "Pliant has initiated a Phase 1b open-label indication expansion trial enrolling three cohorts of patients with NSCLC, tumors with high tumor mutational burden or clear cell renal cell carcinoma. Patients will be treated for 14 days with PLN-101095 dosed at 1,000 mg twice daily as monotherapy, after which pembrolizumab will be added as combination therapy. Enrollment is underway with interim data expected in 2027."

Enrollment status • P1 data • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer

Pliant Therapeutics Announces Presentation of Updated Data from the Phase 1 Trial of PLN-101095 in Patients with ICI-Refractory Solid Tumors at the 2026 AACR Annual Meeting (The Manila Times) - "Confirmed responses deepened with an average maximum tumor reduction from baseline of 89% and median time on treatment increased to 19 months..One confirmed overall complete response, two confirmed overall partial responses, including one patient with a complete response of baseline target lesions, and one unconfirmed partial response were reported in patients with cholangiocarcinoma, non-small cell lung cancer (NSCLC), melanoma and head and neck squamous cell carcinoma, respectively...All responding patients showed large increases (4- to 13-fold vs. baseline) in plasma interferon gamma (IFN-γ) after a 14-day run-in period of monotherapy with PLN-101095. At Week 10, all responders maintained more than a 2-fold increase in IFN-γ....One Grade 3 TRAE was observed."

P1 data • Cholangiocarcinoma • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

Pliant Therapeutics Announces Upcoming Presentation of Phase 1 Clinical Trial of PLN-101095 in Patients with Solid Tumors at the 2026 AACR Annual Meeting (GlobeNewswire)

First-in-human • P1 data • Solid Tumor

Accelerated development plan of PLN-101095 underway with initiation of Phase 1b indication expansion trial (GlobeNewswire) - "Based on the encouraging response data and supportive IFN- γ biomarker data from the Phase 1 trial, the Company is advancing an accelerated clinical development plan of PLN-101095 and has initiated a Phase 1b indication expansion trial. The Phase 1b open-label, single dose trial will enroll three cohorts of patients including NSCLC, clear cell renal cell carcinoma and tumors with high tumor mutational burden....Patients will be treated for 14 days with PLN-101095 dosed at 1,000 mg twice daily as monotherapy, after which pembrolizumab will be added as combination therapy. Study start activities for this trial are underway with first patient enrollment anticipated in second quarter. Interim data is expected in 2027."

P1 data • Trial status • Clear Cell Renal Cell Carcinoma • Non Small Cell Lung Cancer

PLN-101095 Phase 1 data accepted for presentation at AACR Annual Meeting 2026 (GlobeNewswire) - "Data from the Phase 1 trial of PLN-101095 will be the subject of a poster presentation and an oral presentation as part of the Clinical Trials Minisymposium at the upcoming American Association of Cancer Research (AACR) conference to be held April 17-22, 2026, in San Diego, California."

P1 data • Solid Tumor

Pliant Therapeutics…announced interim data from its Phase 1 dose escalation clinical trial evaluating PLN-101095, in combination with pembrolizumab, in patients with immune checkpoint inhibitor (ICI)-refractory advanced or metastatic solid tumors (GlobeNewswire) - "In a heavily pretreated patient population with advanced and/or metastatic solid tumors refractory to ICIs, PLN-101095 demonstrated anti-tumor activity in combination with pembrolizumab. Across the three highest dose cohorts, there were four responders consisting of one confirmed complete response (CR) and three partial responses (PR) (two confirmed, one unconfirmed) out of the 10 secondary ICI refractory patients. Clinical responses were observed in patients with cholangiocarcinoma, melanoma, head and neck squamous cell carcinoma and non-small cell lung cancer (NSCLC)....Final data from this trial will be presented at an upcoming scientific conference....Company to accelerate development of PLN-101095 with initiation of a Phase 1b expansion trial in 2026."

New P1 trial • P1 data • Cholangiocarcinoma • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

Selective targeting of integrins avb8 and avb1 improves anti-tumor responses mediated by immune checkpoint inhibition (SITC 2025) - P1 | "Furthermore, analysis of spleens of EMT6 tumor bearing mice treated with PLN-101095 monotherapy or the combination with anti-PD1 showed enhanced numbers of IFNγ + producing neoantigen-specific T cells, compared to the anti-PD1 and control groups. These data provided rationale for an ongoing, first-in-human phase I clinical trial (NCT06270706) of PLN-101095 in combination with pembrolizumab in solid cancers."

Checkpoint inhibition • IO biomarker • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • GZMB • IFNG • SMAD3 • TGFB1

Pliant Therapeutics Provides Corporate Update and Reports Second Quarter 2025 Financial Results (GlobeNewswire) - "Second Quarter and Recent Developments:...Phase 1 trial of PLN-101095 in solid tumors continues to enroll:...The Phase 1 open-label, dose-escalation trial of PLN-101095 trial as monotherapy and in combination with pembrolizumab is in patients with solid tumors that are resistant to immune checkpoint inhibitors. The trial is currently dosing the fifth of five planned dose cohorts, evaluating PLN-101095 at 2000 mg administered twice daily (BID). Initial data from the two highest dose cohorts of the trial is expected by the end of 2025."

P1 data • Trial status • Solid Tumor

Pliant Therapeutics Announces Interim Phase 1 Data for PLN-101095 in Patients with Immune Checkpoint Inhibitor-Refractory Advanced Solid Tumors (GlobeNewswire) - P1 | N=77 | NCT06270706 | Sponsor: Pliant Therapeutics, Inc. | "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."

P1 data • Oncology • Solid Tumor

Pliant Therapeutics Provides Corporate Update and Reports Fourth Quarter 2024 Financial Results (GlobeNewswire) - "Phase 1 trial of PLN-101095 in solid tumors continues to enroll, with interim data expected in the first quarter 2025....The trial is currently dosing the fourth of five planned dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors."

P1 data • Trial status • Oncology • Solid Tumor

PLN-101095 a selective inhibitor of integrins αvβ8 and αvβ1 augments the therapeutic benefits of immune checkpoint blockade therapy in human tumor histoculture model (SITC 2024) - P1 | "Explants in culture were treated with PLN either alone (50nM and 500nM), with nivolumab (anti PD-1 antibody, 132ug/ml) or in combination for 72 hours. Ethics Approval Donor tissue specimens along with matched blood sample were obtained from consented patients diagnosed with Head and neck squamous cell carcinoma (HNSCC). The Institutional Ethics Committee (IEC) from the sample collection centers approved the protocol (protocol # FCB-PROTOCOL-01) and informed consent for participation in the approved study was obtained from every donor."

Checkpoint block • Checkpoint inhibition • IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • GZMB • IFNG • IL10 • TGFB1 • TNFA

Pliant Therapeutics Provides Corporate Update and Reports Third Quarter 2024 Financial Results (GlobeNewswire) - "Pipeline Programs: Phase 1 trial of PLN-101095 in solid tumors is progressing with dosing of the third of five cohorts:...The Company has completed enrollment in the third of five cohorts in the Phase 1 open-label, dose-escalation trial. In this trial, PLN-101095 is being tested as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in early 2025."

P1 data • Trial status • Solid Tumor

Pliant Therapeutics Provides Corporate Update and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "Phase 1 trial of PLN-101095 in solid tumors is progressing with dosing of the third of five cohorts...The Company is currently enrolling the third of five cohorts in the Phase 1 open label, dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in late 2024 or early 2025....Based on preclinical data, PLN-101325 may have the potential to treat additional indications in organ systems outside of muscle. The Company is currently generating additional evidence in support of potential expansion of the scope of PLN-101325 prior to initiating a Phase 1 trial."

P1 data • Preclinical • Trial status • Genetic Disorders • Muscular Dystrophy • Oncology • Solid Tumor

A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=77 | Recruiting | Sponsor: Pliant Therapeutics, Inc.

Combination therapy • Metastases • Monotherapy • New P1 trial • Oncology • Solid Tumor

Pliant Therapeutics Provides Corporate Update and Reports Fourth Quarter 2023 Financial Results (GlobeNewswire) - "Phase 1 trial of PLN-101095 in solid tumors is enrolling. This is a Phase 1 open label trial of PLN-101095, an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to block TGF-β activation in the tumor microenvironment. The trial is currently dosing the third of five planned dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Preliminary data is expected in late 2024."

P1 data • Trial status • Solid Tumor

Selective targeting of integrins αVβ8 and αVβ1 within the dynamic ecosystem of pancreatic cancer to improve the overall anti-tumour response. (LCC 2024) - "Finally, utilizing patient-derived models of metastatic PDA revealed that both PLN-104 and PLN-101095 significantly blocked tumour growth, improved the response to standard of care (SoC) chemotherapy Gemcitabine/Abraxane, and reduced metastatic spread to distant sites. These data provide scientific rationale for the design of future PLN-101095 and SoC chemotherapy as well as immunotherapy combinations in pancreatic cancer, with Phase I first-in-human oncology studies with PLN-101095 plus ICB already underway."

IO biomarker • Fibrosis • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD8 • KRAS • PDX1 • TGFB1