FDA Grants Fast Track to PLN-101095 Plus Pembrolizumab in Solid Tumors

The FDA has granted fast track designation to PLN-101095, Pliant Therapeutics' oral, small molecule, dual-selective inhibitor of αvβ8 and αvβ1 integrins, in combination with pembrolizumab (Keytruda) for the treatment of solid tumors that are resistant to immune checkpoint inhibitors (ICIs).¹

Fast track designation is intended to facilitate and expedite the development and review of therapies for serious or life-threatening conditions. It gives the PLN-101095 program access to more frequent meetings with the FDA to discuss trial design and development plans, the ability to submit a new drug application on a rolling basis, and eligibility for priority review if the relevant criteria are met.

“While immune checkpoint inhibitors have fundamentally changed the oncology treatment landscape, primary or acquired resistance remains a significant barrier for the majority of patients. This fast track designation underscores the urgent need for innovative therapies for immune checkpoint inhibitor-refractory solid tumors and recognizes the potential of PLN-101095. We look forward to working closely with the FDA as we advance this program,” said Bernard Coulie, MD, PhD, president and CEO of Pliant Therapeutics, in a news release.¹

Trial Design and Interim Data

PLN-101095 is being evaluated in FORTIFY (NCT06270706), a phase 1a/1b, multicenter, open-label dose-escalation and indication-expansion trial assessing the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of PLN-101095 as monotherapy and in combination with pembrolizumab in adults with advanced or metastatic solid tumors who have progressed on an ICI.^1,2 Data from the trial are expected in 2027.¹ The expansion portion is enrolling patients with non–small cell lung cancer (NSCLC), tumors with high tumor mutational burden, and clear cell renal cell carcinoma.³

Interim phase 1 findings cited in support of the designation showed that among patients treated with PLN-101095 at the highest dose tested—1000 mg twice daily in combination with pembrolizumab (cohort 3; n = 6)—the objective response rate was 50%, with all responses confirmed partial responses.⁴ A patient with NSCLC achieved a confirmed partial response with a 74% reduction in tumor size, and a patient with cholangiocarcinoma achieved a confirmed partial response with a 48% reduction in tumor size. An additional response was observed at the 2000-mg dose level (n = 3).

About PLN-101095

PLN-101095 is an oral, small molecule, dual-selective inhibitor of the αvβ8 and αvβ1 integrins. The FDA cleared the investigational new drug application for PLN-101095 in February 2023, and the agent has since advanced through phase 1 dose escalation into the current FORTIFY expansion cohorts.⁵ Pliant's lead program, bexotegrast, an integrin inhibitor for idiopathic pulmonary fibrosis, holds separate FDA fast track and orphan drug designations.¹

REFERENCES

1. Pliant Therapeutics Receives FDA Fast Track Designation for PLN-101095 in Combination with Pembrolizumab for the Treatment of ICI-Refractory Solid Tumors. News release. Pliant Therapeutics, Inc. August 18, 2026. Accessed August 19, 2026. https://tinyurl.com/4tb8p4ur

2. A Phase 1a/1b Multicenter, Open-Label Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of PLN-101095 as Monotherapy and in Combination With Pembrolizumab in Adult Participants With Advanced or Metastatic Solid Tumors Who Have Disease Progression While on an Immune Checkpoint Inhibitor (FORTIFY). ClinicalTrials.gov. Updated June 12, 2024. Accessed August 19, 2026. https://clinicaltrials.gov/study/NCT06270706

3. Pliant Therapeutics Announces Upcoming Presentation at the 2026 American Society of Clinical Oncology Annual Meeting. News release. Pliant Therapeutics, Inc. May 21, 2026. Accessed August 19, 2026. https://tinyurl.com/3wcr8bpm

4. Pliant Therapeutics Announces Interim Phase 1 Data for PLN-101095 in Patients with Immune Checkpoint Inhibitor-Refractory Advanced Solid Tumors. News release. Pliant Therapeutics. March 17, 2025. Accessed August 20, 2026. https://tinyurl.com/4zby5bbb

5. Pliant Therapeutics Announces FDA Clearance of Investigational New Drug Application for PLN-101095, A Novel Integrin Inhibitor for the Treatment of Solid Tumors. News release. Pliant Therapeutics, Inc. February 2, 2023. Accessed August 19, 2026. https://tinyurl.com/yc7hsx9j