PLN-101095 earned an FDA fast track designation in combination with pembrolizumab for solid tumors resistant to immune checkpoint inhibitors.
The FDA has granted fast track designation to the oral, small molecule, dual-selective inhibitor, PLN-101095 in combination with pembrolizumab (Keytruda) for the treatment of solid tumors that are resistant to immune checkpoint inhibitors (ICIs).1
The phase 1a/1b FORTIFY trial (NCT06270706) is currently evaluating PLN-101095 in combination with pembrolizumab.
Responses were observed in patients with cholangiocarcinoma, head and neck squamous cell carcinoma, melanoma, and non–small cell lung cancer (NSCLC).
“While ICIs have fundamentally changed the oncology treatment landscape, primary or acquired resistance remains a significant barrier for the majority of patients,” said Bernard Coulie, MD, PhD, president and chief executive officer of Pliant Therapeutics in a news release.1 “This fast track designation underscores the urgent need for innovative therapies for ICI-refractory solid tumors and recognizes the potential of PLN-101095.”
PLN-101095 selectively inhibits integrins αvβ8 and αvβ1 to help restore antitumor immune activity in tumors that have become resistant to checkpoint blockade.2
The phase 1a/1b, multicenter, open-label trial enrolled patients with advanced or metastatic solid tumors who have received at least 12 prior weeks of anti-PD-1 or anti-PD-L1 treatment.3 Patients were also required to have at least 1 measurable lesion per RECIST 1.1 criteria, an estimated life expectancy of at least 3 months, and no other effective therapeutic options available.
If patients had immune-related medical conditions that put them at greater risk with pembrolizumab, additional malignancies that require treatment, central nervous system metastases, significant cardiac disease, or undergone major surgery within 4 weeks of their first dose of the study, they were not included.
In part 1 of the trial, patients received twice daily doses of PLN-101095 at 250 mg, 500 mg, 1000 mg, or 2000 mg, or 1000 mg 3 times daily, administered as monotherapy in combination with 200 mg of intravenous pembrolizumab every 3 weeks. Part 2 of the trial is evaluating PLN-101095 in combination with the same dose of pembrolizumab in NSCLC, clear cell renal cell carcinoma, and tumor mutational burden-high solid tumors, each in separate cohorts.
Primary end points of the trial are safety, dose-limiting toxicities, and antitumor activity. Secondary end points include duration of response and pharmacokinetic measures.
The disease control rate from previoulsy reported data was 60% with a median time on treatment among responders or 15 months as of data cutoff.2 Regarding safety, common treatment-emergent adverse effects (TEAEs) that were previously reported among all evaluable patients (n = 16) were rash (50%), diarrhea (19%), and anemia (19%) with 31% of patients experiencing serious TEAEs.
With fast track designation now in place, FORTIFY will progress toward additional data expected to report in 2027.1
