Phase 1a1b Study of PLN-101095 with Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors Showing Disease Progression on Immune Checkpoint Inhibitors

What this Trial Is About

Researchers are conducting a Phase 1a1b open-label study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PLN-101095 combined with pembrolizumab in adults with advanced or metastatic solid tumors. Participants must have tumors for which pembrolizumab is indicated and must show disease progression or relapse after at least three months of pembrolizumab treatment. The study includes consecutive dose-escalation and dose-expansion cohorts to explore different dosing levels and tumor types. The study has two main parts Part 1 uses a Bayesian optimal interval design for dose escalation with accelerated titration to test increasing doses of PLN-101095 combined with pembrolizumab, while Part 2 uses Simons two-stage design for dose expansion. Doses of PLN-101095 range from 250 mg twice daily up to 2000 mg twice daily or 1000 mg three times daily, given in combination with pembrolizumab administered intravenously every three weeks. Participants in expansion cohorts include those with non-small cell lung cancer, clear cell renal cell carcinoma, or tumor mutational burden-high solid tumors, receiving PLN-101095 as monotherapy or combined with pembrolizumab. Participants will be monitored for safety and tolerability from first dose through 16 weeks after treatment ends, and anti-tumor activity will be measured from first dose until disease progression or death. Pharmacokinetics of PLN-101095 will be assessed at specified time points. The study evaluates participants measurable lesions and organ function, with follow-up assessments for adverse events and treatment response. The total duration varies depending on treatment response and tolerability, with ongoing monitoring throughout the study period.

A Phase 1 Study of PLN-101095 in Adults With Advanced or Metastatic Solid Tumors