Here's an interesting development in cancer treatment that the market apparently didn't love: Pliant Therapeutics Inc. (PLRX) released Phase 1 trial data Thursday showing its experimental drug PLN-101095 can revive responses in patients whose cancers had essentially learned to ignore checkpoint inhibitor immunotherapy. The catch? The stock tanked anyway, dropping over 20%.
The trial tested PLN-101095 alongside Merck & Co. Inc.'s (MRK) blockbuster Keytruda (pembrolizumab) in patients with advanced or metastatic solid tumors that had become refractory to immune checkpoint inhibitors. These are particularly challenging cases where the immune system's brakes can't be released anymore using standard immunotherapy.
PLN-101095 represents the fourth clinical-stage candidate from Pliant's integrin-based drug development platform, and the early results suggest it might be onto something meaningful in a patient population with limited options.
The Response Data
Among the three highest dose cohorts, four out of 10 secondary ICI-refractory patients responded to the combination therapy. That included one confirmed complete response and three partial responses (two confirmed, one unconfirmed). For context, these are heavily pretreated patients whose cancers had stopped responding to checkpoint inhibitors.
The responses weren't limited to one cancer type either. Clinical activity showed up across cholangiocarcinoma, melanoma, head and neck squamous cell carcinoma, and non-small cell lung cancer. The median time on treatment for these responding patients hit 15 months, which is notable for this patient population.
Beyond the clear responders, 60% of secondary refractory patients demonstrated stable disease or tumor reduction, suggesting the drug might offer disease control benefits even without dramatic shrinkage.
The Biomarker Story
Here's where it gets interesting from a mechanism standpoint. All responding patients showed substantial increases in plasma interferon gamma after a 14-day run-in period with PLN-101095 alone. We're talking 4- to 13-fold increases compared to baseline. Interferon gamma is a cytokine that plays a central role in the immune system's ability to fight infections and disease, including cancer.
The flip side matters too: patients who didn't respond showed no meaningful increases in interferon gamma. That suggests the biomarker might help predict which patients will benefit, though more data is needed to confirm that relationship.
Safety and Next Steps
PLN-101095 was generally well tolerated across all tested doses and showed a dose-dependent pharmacokinetic profile, meaning drug levels in the blood increased predictably with higher doses.
Pliant plans to move quickly, initiating a Phase 1b indication expansion trial in 2026 that will assess non-small cell lung cancer and other tumor types where integrin inhibition has strong mechanistic rationale. Final data from the current dose escalation trial will be presented at an upcoming scientific conference.
Stock Movement: Despite the clinical progress, Pliant Therapeutics (PLRX) shares closed down 20.45% at $1.22 on Thursday, trading near the 52-week low of $1.10. Sometimes promising early-stage data isn't enough to overcome broader market concerns about a small biotech's path forward.