Pliant Therapeutics Reports Interim Phase 1 Results for PLN-101095 in Advanced Solid Tumors

Pliant Therapeutics, a biopharmaceutical company based in South San Francisco, recently shared promising interim data from its ongoing Phase 1 clinical trial. This trial investigates the potential of PLN-101095, a small molecule inhibitor targeting integrins αvβ8 and αvβ1, used in combination with pembrolizumab for treating patients with advanced or metastatic solid tumors that are refractory to immune checkpoint inhibitors (ICIs).

The trial is structured in a dose-escalation format and has progressed through three out of five potential cohorts. In these cohorts, PLN-101095 was administered at different doses: 250 mg, 500 mg, and 1000 mg, all given orally twice a day. Following this, patients received a combination treatment of PLN-101095 and pembrolizumab, the latter being administered at 200 mg intravenously every three weeks. Imaging scans were performed at multiple stages: the start, Day 14, Week 10, and continued every eight weeks thereafter, to assess the treatment's impact.

Encouragingly, the results from cohort three, where six patients received the 1000 mg BID dose of PLN-101095, showed a 50% objective response rate (ORR). Specifically, three patients exhibited partial responses. These patients, suffering from different types of tumors, saw significant tumor size reductions and have continued their treatment.

The patient responses in this cohort were notable: a patient with non-small cell lung cancer (NSCLC) experienced a 74% reduction in tumor size by Week 18, marking an initial response by Week 10. Another patient with cholangiocarcinoma showed a 48% tumor reduction by Week 42, with an initial response at Week 34. Meanwhile, a melanoma patient achieved a 42% reduction in tumor size by Week 27, with the first signs of response observed at Week 18.

PLN-101095 demonstrated a generally favorable safety profile across all doses, with tolerability noted as a positive outcome of the trial stages thus far. The ongoing study is now enrolling participants for the fourth cohort, which is testing a higher frequency of administration at 1000 mg, three times daily.

The investigational drug PLN-101095 works by inhibiting integrins αvβ8 and αvβ1, critical in the activation of transforming growth factor-β (TGF-β), which is known to create an immune-suppressive tumor microenvironment. By blocking these integrins, PLN-101095 may help in stimulating an immune response by enhancing immune cell infiltration into tumors, potentially overcoming resistance seen with standard ICI therapies.

Pliant Therapeutics is committed to the development of novel treatments for fibrotic diseases and cancer. PLN-101095 is a part of their broader pipeline, alongside bexotegrast (PLN-74809), which is being developed for idiopathic pulmonary fibrosis, and PLN-101325, a candidate targeting muscular dystrophies.

As the trial progresses, Pliant's Chief Medical Officer, Éric Lefebvre, M.D., expressed optimism about these initial findings, especially given the challenging nature of treating refractory patient populations. The company anticipates sharing more comprehensive results from this trial in the future, focusing on the efficacy and safety of PLN-101095 as a potential new treatment avenue for resistant tumors.