First-in-human phase 1/2a study of PBP1510 (anti-PAUF mAb) in advanced/metastatic pancreatic adenocarcinoma: Safety results from early combination cohorts.

e16363 Background: Pancreatic Adenocarcinoma Up-regulated Factor (PAUF), a protein overexpressed in pancreatic adenocarcinoma, contributes to metastasis and chemoresistance. PBP1510 is a first-in-class humanized anti-PAUF monoclonal antibody (mAb) with tumor-suppressing potential. PAUF-I (NCT05141149) is an ongoing, open-label, multi-national clinical study to evaluate PBP1510 in advanced/metastatic pancreatic adenocarcinoma patients. Safety results from the first two combination cohorts (PBP1510 and gemcitabine) are presented here. Methods: In Phase 1, safety, tolerability and pharmacokinetics (PK) are evaluated in a 3 + 3 dose-escalation design with 5 ascending doses (1, 3, 6, 10, and 15 mg/kg) of intravenous PBP1510 as monotherapy and in combination with gemcitabine (1000 mg/m 2 ) in 28-day cycles. The Dose-Limiting Toxicity (DLT) observation period is 28 days. Tumor assessments are performed every 8 weeks from the first PBP1510 dose. Key eligibility criteria include locally advanced/metastatic pancreatic adenocarcinoma, disease progression following at least 1 previous line of chemotherapy, at least 1 measurable lesion by RECIST v1.1, ECOG value of 0-1, life expectancy of ≥ 3 months, and adequate baseline organ functions. Results: Six patients [3M, 3F; age 65-77 (median: 73.5) years; 100% metastatic] exposed to 1-5 (median: 2.5) prior lines of systemic therapies were enrolled to receive PBP1510 at 1 mg/kg (N = 3), and 3 mg/kg (N = 3) in combination with gemcitabine. At data cut-off (6 Jan 2025), patients had received 1-6 treatment cycles (median: 2), and treatment for 3 patients in the 3 mg/kg cohort is ongoing. Overall, 73 treatment-emergent adverse events (TEAEs) were reported in 5 patients (n = 73; N = 5). Most TEAEs were NCI-CTCAE Grade 1 (n = 38; N = 5) or Grade 2 (n = 26; N = 5). The most common Grade 1 and Grade 2 TEAEs were diarrhea (n = 4; N = 3) and hypokalemia (n = 3; N = 3), respectively. Of the Grade 3 TEAEs (n = 9; N = 4), the most reported were platelet count decreased (n = 3; N = 1). Of all TEAEs, 31 events were related to both PBP1510 and gemcitabine (n = 31; N = 4). The most reported TEAEs related to PBP1510 only and to gemcitabine only were diarrhea (n = 2; N = 1) and platelet count decreased (n = 8; N = 1), respectively. Most treatment-related TEAEs were Grade 1 (n = 14; N = 3) or Grade 2 (n = 13; N = 4). Clinically significant laboratory abnormalities were observed for hematology (n = 7; N = 5; Grade 1-3) and blood chemistry (n = 4; N = 2; Grade 1-2). No DLTs and no serious TEAEs were reported. The evaluation of clinical activity and PK is ongoing. Conclusions: Interim safety data from the dose-escalation of PBP1510 demonstrate acceptable tolerability at up to 3 mg/kg in combination with gemcitabine in metastatic pancreatic adenocarcinoma patients who had failed previous treatment(s). Clinical evaluation of PBP1510 in higher dose-level combination cohorts is ongoing. Clinical trial information: NCT05141149 .