LAPIS: Randomized phase 3 trial of chemotherapy (CTX) with and without pamrevlumab (PAM) for locally advanced pancreatic cancer (LAPC).

675 Background: PAM improved response, surgical eligibility, and resection rates when combined with CTX in phase 1/2 LAPC trials (NCT01181245; NCT02210559). LAPIS (NCT03941093) evaluated efficacy and safety of PAM + CTX in unresectable LAPC. Methods: LAPIS was a global, double-blind, placebo-controlled phase 3 trial of adults with treatment-naïve, -confirmed unresectable LAPC. Patients received (randomized 1:1) PAM (35 mg/kg Q2W) or placebo (PBO) plus CTX (gemcitabine + nab-paclitaxel [GnP] or FOLFIRINOX [FFX] per standard protocol) for up to six 28-day cycles. based on changes in -9, on FDG-PET, resectability, with final surgical decision made by surgeon. Primary endpoint: overall survival (OS); secondary endpoints: event-free survival (EFS), progression-free survival (PFS), and objective response rate (ORR. Safety (including treatment-emergent adverse events [TEAEs]) was evaluated in patients who received treatment. Results: 143 and 141 patients (median [range] age, 65.0 [31–90] yrs; 53.2% male) were randomized to PAM and PBO arms. 142 and 141 received treatment: GnP, 114 (79.7%) and 112 (79.4%); FFX, 28 (19.6%) and 29 (20.6%). PAM (64.8%) and 96 PBO (68.1%) patients completed 6 treatment cycles. . Survival similar for PAM and PBO arms (Table) and did not differ by. For PAM + FFX vs PBO + FFX, respiratory, thoracic and mediastinal disorders (39.3% vs 27.6%) and skin and subcutaneous tissue disorders (53.6% vs 37.9%) occurred >10% more with PAM; TEAE frequencies were similar with PAM + GnP and PBO + GnP. One treatment-related death occurred in PAM arm. Conclusions: LAPIS contained important LAPC trial innovations: pre/post-CTX FDG-PET imaging, objective criteria for surgical intervention, external surgical review panel, and composite EFS measurement. Addition of PAM to CTX was not associated with additional toxicity but did not improve survival outcomes for unresectable LAPC. Clinical trial information: NCT03941093 . LAPIS endpoints. PAM arm (n=143) PBO arm (n=141) OS, months, median (95% CI) events=118 (82.5%)17.25 (15.47, 18.89) events=112 (79.4%)17.94 (14.59, 20.34) HR (95% CI)1.08 (0.83, 1.41)p=0.55 EFS, a months, median (95% CI) events=99 (69.2%)5.72 (5.59, 6.01) events=102 (72.3%)5.78 (5.62, 6.37) HR (95% CI)1.05 (0.78, 1.39) PFS, months, median (95% CI) events=48 (33.6%)9.36 (7.75, 11.79) events=44 (31.2%)9.40 (7.69, 10.84) HR (95% CI)1.01 (0.65, 1.56) ORR, n (%) 43 (30.1) 64 (45.4) OR (95% CI)0.50 (0.31, 0.82) Complete response 0 0 Partial response 43 (30.1) 64 (45.4) CI, confidence interval; HR, hazard ratio; OR, odds ratio. a Earliest of 1) failure to achieve local disease-free status at end of treatment and/or after surgery; 2) local or distant recurrence/progression; or 3) death.