The phase 3 LAPIS trial, presented at the 2025 Gastrointestinal Cancer Symposium, revealed that adding pamrevlumab to chemotherapy did not improve survival outcomes for patients with locally advanced, unresectable pancreatic cancer (LAPC). While the combination did not incur additional toxicity, it failed to demonstrate a statistically significant benefit in overall survival compared to chemotherapy alone.
The LAPIS trial enrolled 284 patients, randomized 1:1 to either pamrevlumab (35 mg/kg every 2 weeks) plus chemotherapy or placebo plus chemotherapy. The chemotherapy regimen consisted of gemcitabine, nab-paclitaxel, or FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin), administered in six 28-day cycles. The primary endpoint was overall survival (OS), with secondary endpoints including event-free survival (EFS), progression-free survival (PFS), and overall response rate (ORR).
Key Findings from the LAPIS Trial
Topline results indicated a median overall survival (OS) of 17.3 months in the pamrevlumab arm compared to 18.0 months in the placebo arm (HR, 1.08; 95% CI, 0.83-1.41; P = .5487). The median EFS was 5.7 months in the combination arm and 5.8 months in the placebo arm (HR, 1.05; 95% CI, 0.78-1.39). Median progression-free survival (PFS) was 9.4 months in both the pamrevlumab plus chemotherapy arm and the placebo arm (HR, 1.01; 95% CI, 0.65-1.56). The overall response rate (ORR) was 30.1% in the pamrevlumab arm and 45.4% in the placebo arm (OR, 0.50; 95% CI, 0.31-0.82).
Surgical Outcomes and Safety
Surgical outcomes were similar between the two arms. Specifically, 67.6% of patients in the pamrevlumab arm and 65.7% in the placebo arm completed six cycles of chemotherapy and were considered for surgery. Surgical exploration eligibility was met by 14.7% of patients in the pamrevlumab arm and 20.0% in the placebo arm, with “Resection Achieved” status reported in 8.8% and 8.6% of patients, respectively. Adverse effect severity and frequency, as well as surgical complications, were comparable between the groups. Notably, one patient in the combination arm died from pneumonia, considered treatment-related.
Insights and Limitations
According to Dr. Vincent Picozzi, a medical oncologist from Virginia Mason Franciscan Health, “The LAPIS findings provide valuable insights into the challenges of treating LAPC, and the LAPIS trial design innovations and end points may influence future trial design by enabling shorter, more targeted trials.”
Limitations of the study included the inclusion of patients with non-reconstructible disease at baseline, which may have limited the potential for curative resection and survival. Additional limitations involved not requiring staging laparoscopy, variability in supportive care, and the trial's occurrence during the global pandemic, which may have negatively impacted survival outcomes.
