Abstract CT061: Preliminary safety results from the first-in-human phase 1/2a study of PBP1510 (anti-PAUF mAb) in advanced/metastatic pancreatic adenocarcinoma

Abstract Background Pancreatic Adenocarcinoma Up-regulated Factor (PAUF) protein is overexpressed in pancreatic adenocarcinoma and is reported to contribute to metastasis and chemoresistance. PBP1510, a novel first-in-class humanized monoclonal antibody (mAb), is anticipated to demonstrate anti-tumor effects by neutralization of PAUF functions. PAUF-I (NCT05141149) is an ongoing, open-label, multi-center clinical study to evaluate PBP1510 in advanced/metastatic pancreatic adenocarcinoma patients. Here, we present preliminary safety results from 3 monotherapy cohorts in Phase 1. Methods A 3 + 3 dose-escalation design is used to investigate the safety, tolerability and pharmacokinetics (PK) of 5 ascending dose levels (1, 3, 6, 10, and 15 mg/kg) of intravenous PBP1510 as monotherapy or in combination with gemcitabine (1000 mg/m2) in 28-day cycles. Tumor assessments are performed every 8 weeks from the first dose of PBP1510. Patients with advanced or metastatic pancreatic adenocarcinoma whose disease progressed following at least one prior line of standard chemotherapy are eligible for enrollment. Other important criteria include having at least one measurable lesion as per RECIST v1.1, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate baseline organ functions. Results Twelve patients (5M, 7F; median age 62.5 years; 100% metastatic), exposed to 2-5 prior lines of systemic therapies (median: 2) were enrolled to receive PBP1510 monotherapy at 1 mg/kg (N=3), 3 mg/kg (N=3), and 6 mg/kg (N=6). As of the cut-off date, patients completed 1-3 treatment cycles in the study (median: 2), with treatment ongoing for 3 patients. No dose-limiting toxicities were observed. A total of 56 treatment related adverse events (TRAEs) were reported in 11 patients (n=56; N=11). The most common TRAEs were transient events of asthenia (n=8; N=6), diarrhea (n=5; N=3), and anemia (n=4; N=1). Most TRAEs were NCI-CTCAE Grade 1 (n=40; N=10) or Grade 2 (n=13; N=3). Of the Grade 3 TRAEs (n=3; N=3), asthenia and GGT increased were reported in the 1 mg/kg cohort. A Grade 3 TRAE of cerebrovascular accident was reported in the 6 mg/kg cohort in a patient with a history of thromboembolism and hypertension, for which a possible relationship to PBP1510 could not be excluded. Adopting a conservative approach, the 6 mg/kg cohort was expanded to include 3 additional patients. No TRAEs of concern were observed in the expanded cohort. The evaluation of clinical activity and PK is ongoing. Conclusion Interim safety data from dose-escalation of the first-in-class PBP1510 demonstrates acceptable tolerability up to 6 mg/kg in advanced/metastatic pancreatic adenocarcinoma patients who have failed previous lines of treatment. Clinical evaluation of PBP1510 in higher cohorts, including combination therapy with gemcitabine, is ongoing. Citation Format: Daniel A. King, David Tai, Jaime Feliu Batlle, Jamie Kim, Kedar Diwakar Mandakhalikar, Mei Li Lim, Sumita Pradhan, Yun-Yong Park. Preliminary safety results from the first-in-human phase 1/2a study of PBP1510 (anti-PAUF mAb) in advanced/metastatic pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT061.