LAPIS: A Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Neoadjuvant Pamrevlumab With Chemotherapy for Patients With Locally Advanced Pancreatic Cancer

PURPOSE Pamrevlumab demonstrated favorable safety and therapeutic potential in locally advanced pancreatic cancer (LAPC) in phase I/II trials (ClinicalTrials.gov identifiers: NCT01181245 ; NCT02210559 ). LAPIS (phase III; ClinicalTrials.gov identifier: NCT03941093 ) evaluated the efficacy and safety of adding pamrevlumab versus placebo to chemotherapy for patients with LAPC. METHODS Eligible patients (randomly assigned 1:1) received investigator's choice of chemotherapy (gemcitabine plus nab-paclitaxel or folinic acid, fluorouracil, irinotecan, and oxaliplatin per the standard protocol) with either pamrevlumab (35 mg/kg every 2 weeks on days 1 and 15 before chemotherapy; additional dose on day 8 of cycle 1; arm A) or placebo (arm B) for up to six cycles. Patients were assessed for surgical eligibility based on a composite of biomarkers (carbohydrate antigen 19-9, fluorodeoxyglucose positron emission tomography FDG-PET imaging, RECIST v1.1 response criteria, and resectability status), guided by an independent surgical review panel. The primary end point was overall survival (OS). Treatment-emergent adverse events were monitored to evaluate safety. RESULTS Of 284 patients, 143 and 141 were randomly assigned to arms A and B, respectively (median range age, 65.0 31-90 years; 53.2% male). The median OS was 17.3 versus 17.9 months for arms A and B, respectively, and the primary end point was not met (hazard ratio 95% CI, 1.08 0.83 to 1.41; P = .5487). No appreciable increase in toxicity was noted in the pamrevlumab arm. One pamrevlumab-related death occurred in arm A. CONCLUSION LAPIS did not meet its primary end point in this large, phase III trial featuring a design including FDG-PET imaging for response assessment, defined surgical eligibility criteria, an independent surgical review panel, and a composite event-free survival end point, collectively enhancing assessment rigor and clinical applicability and potentially establishing future standards for LAPC trials.