Abstract 983: Design and methodology of LAPIS, an ongoing, phase III trial of neoadjuvant pamrevlumab (pam) with chemotherapy (CT) in patients (pts) with unresectable, locally advanced pancreatic cancer (LAPC)
Authors: Picozzi Vincent J. , Raza Syed , Li Jack , Carrier Ewa 
Published: April 2023

Abstract
Background: LAPC is associated with a median overall survival (OS) of 15-18 mos in contemporary clinical trials. CT is typically the initial treatment, and subsequent surgical resection with curative intent is rare. Pam is a fully human monoclonal antibody that inhibits the effects of connective tissue growth factor. Phase I and II trials (NCT01181245 and NCT02210559) of CT+pam provided the rationale for a Phase III study of pts with LAPC. CT plus pam/placebo (PBO) is being evaluated in the Phase III LAPIS trial (NCT03941093).
Objective: LAPIS is evaluating the efficacy and safety of CT+pam/PBO as first-line/neoadjuvant therapy in unresectable LAPC.
Methods: LAPIS is a global, Phase III, PBO-controlled trial with six cycles of CT+pam/PBO therapy given in a first-line/neoadjuvant setting, surgical eligibility using protocol-specific response criteria, surgery, and follow-up periods, including long-term follow-up for OS. Major eligibility criteria include adults (≥18 yrs of age); ECOG PS of 0-1; histologic/cytologic confirmation of pancreatic cancer; LAPC diagnosis considered unresectable by standard criteria (NCCN v2.2018 and reviewed by central radiology); measurable disease by RECIST v1.1; and treatment-naïve status. Pts were randomized 1:1 to pam+investigator’s choice CT (gemcitabine 1,000 mg/m2+nab-paclitaxel 125 mg/m2; or either FOLFIRINOX [5-fluoruracil 400 mg/m2+folinic acid/leucovorin 400 mg/m2; 5-fluoruracil 2,400 mg/m2; irinotecan 180 mg/m2; oxaliplatin 85 mg/m2; or mFOLFIRINOX [folinic acid/leucovorin 400 mg/m2; 5-fluoruracil 2,400 mg/m2; irinotecan 180 mg/m2; oxaliplatin 85 mg/m2]), or CT+PBO, then stratified by unreconstructable disease (yes/no) and geographic region. Pts received six cycles (24 wks) of first-line therapy prior to surgical eligibility decision. Surgical eligibility was defined per protocol for pts with ≥1 of the following: decline in carbohydrate antigen 19-9 ≥50%; FDG-PET value decrease by ≥30%; radiographic downstage to resectable/borderline resectable criteria per NCCN. Surgical recommendation (resect or not) is provided by the central surgical board. Final decisions on surgery remain with site surgeons. Primary endpoint is OS. Key secondary endpoints include event-free survival [EFS, defined as time to “treatment failure” based on earliest occurrence of 1) failure to achieve local disease-free status at end of treatment and/or after surgery; 2) local or distant recurrence; or 3) death], progression-free survival (PFS), and objective response rate (ORR; complete or partial response) by RECIST v 1.1. Safety (including treatment-emergent adverse events) is evaluated throughout the study, Days 28 and 60 after last CT dose, and Day 90 post-surgery. LAPIS enrollment is complete (N=284). Study completion is estimated for early 2024.
Citation Format: Vincent J. Picozzi, Syed Raza, Jack Li, Ewa Carrier. Design and methodology of LAPIS, an ongoing, phase III trial of neoadjuvant pamrevlumab (pam) with chemotherapy (CT) in patients (pts) with unresectable, locally advanced pancreatic cancer (LAPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 983.