Presenter(s)
T. A. Aguilera1, J. M. Frakes2, J. A. Dorth3, J. M. Caster4, M. Ghaly5, E. B. Ludmir6, S. K. Seung Jr7, K. W. Merrell8, S. Al Mutar9, G. Khan10, B. Zaki11, R. A. Kuehnle12, G. V. Walker13, S. Apisarnthanarax14, J. M. Herman15, S. Zhang16, J. M. M. Sorensen17, and S. Hoffe2; 1Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, 2H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, 3Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 4Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, 5Northwell, New Hyde Park, NY, 6Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7The Oregon Clinic, Portland, OR, United States, 8Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 9Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas, TX, 10Department of Medical Oncology, Henry Ford Cancer Institute, Detroit, MI, 11Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 12UT Health San Antonio, San Antonio, TX, 13Banner MD Anderson Cancer Center, Gilbert, AZ, 14Department of Radiation Oncology, University of Washington, Seattle, WA, 15Department of Radiation Medicine, Northwell, New Hyde Park, NY, 16UT Southwestern Medical Center, Dallas, TX, 17Galera Therapeutics, Malvern, PA
Purpose/Objective(s):
Dose-escalated stereotactic ablative radiotherapy (SAbR) for localized pancreatic cancer may improve outcomes but is limited by concern for gastrointestinal toxicity. In a prior phase Ib/II study (NCT03340974), a selective superoxide dismutase mimetic demonstrated favorable safety and preliminary signals of enhanced disease control when combined with dose escalated SAbR. GRECO-2 (NCT04698915) was designed to evaluate the survival impact of adding rucosopasem to SAbR in localized pancreatic cancer.
Materials/Methods:
GRECO-2 is an international, multicenter, randomized, double-blind, placebo-controlled phase II trial of SAbR (50 Gy in 5 fractions) ± rucosopasem in borderline resectable or locally advanced pancreatic cancer. Patients without progression after 4 months (m) of multiagent chemotherapy were randomized 1:1 to receive SAbR with rucosopasem (100 mg IV before each fraction) or placebo. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, locoregional control, and time to metastasis, and acute grade =3 toxicity.
Results:
The trial enrolled 177 of 220 planned patients across 30 centers in November of 2023 prior to closure for futility after an early review. Following generation of a PI consortium across centers we conducted a single data update in 2026. Of the 177 patients enrolled we collected long term follow up data for vital status from 114 patients with median follow up of 13m revealing a median survival from randomization of 15m for placebo and 12m in the rucosopasm arm (log rank p=0.088). Median survival was 20 and 19m from diagnosis (log rank p=0.113). The two-year overall survival of the whole group was 34%. We were able to collect local and distant recurrence data from 92 patients with a median follow up of 15m from randomization. The median local failure was not reached, and the 12 and 18m local failure free survival was no different between groups at 84.5% and 74.7% respectively. The 6, 12 and 18m distant failure free survival for 92 of the patients was 75.5%, 56.8% and 38.9%.
Conclusion:
In this incomplete review of outcomes, the addition of rucosopasem to dose-escalated SAbR across a diversity of centers and treatment approaches did not improve survival or disease control in localized pancreatic cancer. Durable local control was observed following SAbR, with median local failure-free survival not reached, whereas distant progression remained frequent, underscoring the need for more effective systemic therapies to complement aggressive local treatment.
