Scientific publications
A Phase Ib/II Randomized Clinical Trial of Oleclumab with or without Durvalumab plus Chemotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma. Scientific Publication
Andrew L Coveler 1 , Matthew J Reilley 2 , Mark Zalupski 3 , Teresa Macarulla 4 , Christos Fountzilas 5 , Mariano Ponz-Sarvisé 6 , Adnan Nagrial 7 , Nataliya V Uboha 8 , Sophia Frentzas 9 , Michael Overman 10 , Anne Noonan 11 , Wells A Messersmith 12 , Nick Pavlakis 13 , Niharika B Mettu 14 , Ina Bisha 15 , Ying Wang 16 , Paul Smith 17 , Elina Murtomaki 18 , Agata A Bielska 16 , Veronique Bragulat 18 , Zachary A Cooper 19 , Rakesh Kumar 19 , David R Spigel 20
Purpose: Pancreatic ductal adenocarcinoma upregulates CD73, potentially contributing to immune surveillance evasion. Combining oleclumab (CD73 inhibitor) and durvalumab with chemotherapy may identify an effective treatment option.
Patients and methods: We describe a multicenter phase Ib/II randomized clinical trial in patients with metastatic pancreatic ductal adenocarcinoma, untreated (cohort A) or previously received gemcitabine-based chemotherapy (cohort B; NCT03611556). During escalation, patients received oleclumab 1,500 or 3,000 mg, durvalumab 1,500 mg, and gemcitabine plus nab-paclitaxel (GnP; cohort A; n = 14) or modified FOLFOX (cohort B; n = 11). During expansion, cohort A patients (n = 170) were randomized to GnP (arm A1), oleclumab [recommended phase II dose (RP2D)] with GnP (arm A2), or oleclumab (RP2D) with durvalumab plus GnP (arm A3). Primary objectives were safety (escalation) and objective response rate (expansion). Secondary objectives included progression-free survival (PFS) and overall survival (OS).
Results: During escalation, 1/11 patients from cohort B (oleclumab 3,000 mg) experienced two dose-limiting toxicities. Oleclumab's RP2D was 3,000 mg. During expansion, grade ≥3 treatment-related adverse events occurred in 67.7% (42/62) of patients in A1, 73.7% (28/38) in A2, and 77.1% (54/70) in A3. The objective response rate was 29.0%, 21.1%, and 32.9% in A1, A2, and A3, respectively (A1 vs. A3; P = 0.650). PFS [HR = 0.72; 95% confidence interval (CI), 0.47, 1.11] and OS (HR = 0.75; 95% CI, 0.50-1.13) were similar for A3 versus A1. Patients with high CD73 expression had improved PFS and OS in A3 versus A1, although this should be interpreted with caution.
Conclusions: Although the safety profile was acceptable, this study did not meet its primary efficacy endpoint.
CITATION Clin Cancer Res. 2024 Oct 15;30(20):4609-4617. doi: 10.1158/1078-0432.CCR-24-0499
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