FDA Grants Fast Track Designation to Pliant's Oral Integrin Inhibitor PLN-101095 for Checkpoint-Refractory Solid Tumors

Fast Track attaches to the combination

Fast Track applies to the combination, not to PLN-101095 alone, and to solid tumors resistant to immune checkpoint inhibitors. Pliant listed the practical consequences in its announcement: more frequent meetings with the agency on trial design and development plans, the ability to submit a New Drug Application on a rolling basis, and eligibility for priority review if the criteria are met later. Qualification turns on available clinical and non-clinical data showing potential to address an unmet need, a standard the agency applies before efficacy is established. Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant, said: "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."

Three confirmed responders averaged an 89% lesion reduction

The clinical record behind the designation comes from the dose-escalation portion of FORTIFY, presented at the AACR 2026 annual meeting by Timothy A. Yap of the University of Texas MD Anderson Cancer Center with a Feb. 27, 2026 cutoff. Sixteen patients with 10 tumor types received PLN-101095 monotherapy at doses from 250 mg twice daily to 2,000 mg twice daily before pembrolizumab was added. Among the secondary-refractory subgroup treated at the higher twice-daily doses, investigators reported one confirmed complete response, two confirmed partial responses and one unconfirmed partial response, in cholangiocarcinoma, non-small cell lung cancer, melanoma and head and neck squamous cell carcinoma. The three confirmed responders had a median time on treatment of 19 months and an average reduction in baseline target lesions of 89%. Rash was the most common treatment-related adverse event, all grade 1 or 2, with one grade 3 event and two discontinuations across the cohort.

Pliant has built a biomarker case around the 14-day monotherapy window. Responding patients showed 4-fold to 13-fold increases in plasma interferon gamma after the run-in, held more than a 2-fold increase at week 10, and had elevated plasma PD-L1. At an AACR drug discovery conference in July the company added CXCL9 and granzyme B increases in the same responders, and no non-responder showed those changes.

Yap described the mechanism when he presented the escalation results:

One of the ways that the tumor microenvironment can suppress responses to immune checkpoint inhibitors is through a process that is activated by integrins to upregulate TGF-beta. PLN-101095 is designed to inhibit the integrins before they can ever do that, which gives it significant potential to stimulate or reinvigorate the immune response to cancer.

How the trial defines refractory

FORTIFY's registry record, last updated Aug. 3, 2026, sets the entry criteria the designation language leaves vague. Patients must have had at least 12 weeks of continuous anti-PD-1 or anti-PD-L1 treatment, then documented radiographic progression while on it or within 12 weeks of the last dose. For the expansion portion, patients must also have shown prior clinical benefit, defined as a complete or partial response at any point or stable disease lasting at least six months. Pliant said in its Aug. 11 quarterly update that enrollment is running ahead of schedule, with interim data expected in 2027.

Why This Matters to the APO|APE Reader

One of the three expansion cohorts enrolls on tumor mutational burden rather than histology, and neither the release nor the registry record names the assay or the cutoff used to call a tumor TMB-high. The reference point is FoundationOne CDx at 10 mutations per megabase, approved as pembrolizumab's companion diagnostic in TMB-high solid tumors in June 2020. Whichever assay FORTIFY uses will determine how a positive result in that cohort translates to a testing pathway, and Pliant's own timeline puts that question a full year out.