Targeted Agent Receives FDA FTD for Pancreatic Ductal Adenocarcinoma

The FDA has granted fast track designation to anti–pancreatic adenocarcinoma up-regulated factor (PAUF) monoclonal antibody PBP1510 (Ulenistamab) as a treatment for patients who have unresectable or metastatic pancreatic adenocarcinoma with relapsed/refractory disease following at least 1 line of prior therapy, according to a press release from Prestige Biopharma.

The primary end points in phase 1 of the study assessing PBP1510 include safety and tolerability and dose limiting toxicities. In phase 2, the primary end point is the safety and efficacy of PBP1510 plus gemcitabine.

The agent targets PAUF, a known tumor-specific protein that is found to be overexpressed in most patients with pancreatic cancer. This overexpression plays a notable role in key cell functions such as proliferation, migration, invasion, and cell growth, as well as influencing the occurrence of acquired resistance to chemotherapeutics.

Experts designed PBP1510 to potentially prevent fast disease progression and target the aforementioned mechanisms that may interfere with the efficacy of current treatment options. Thus far, inhibiting PAUF overexpression has demonstrated early efficacy in preclinical models, and PBP1510 is also being investigated as part of a first-in-human phase 1/2a study (NCT05141149). The investigators hope that the study will confirm the validity of the agent’s synergy and anti-tumor activity when combined with gemcitabine.

The first half of the study will focus on dose escalation of PBP1510 both alone and in combination with gemcitabine. Additionally, the phase 2a portion of the study will identify the recommended phase 2 dose (RP2D) and assess the safety and efficacy of PBP1510 at the RP2D in combination with gemcitabine.

The study has an estimated enrollment of 80 patients with pancreatic cancer. Patients who enroll will receive one of several doses of PBP1510 including 1 mg/kg, 3 mg/kg, 6 mg/kg, 10 mg/kg, or 15 mg/kg with or without 1000 mg/m2 of gemcitabine.

The primary end points in phase 1 of the study include safety and tolerability as well as dose limiting toxicities, and the primary end point of phase 2 is the safety and efficacy of the combination regimen. Secondary end points in phase 2 include progression-free survival, overall survival, and duration of response. Additionally, exploratory end points in phase 1 of the study include objective response rate, and pre- and post-treatment PAUF tumor expression.

The study included patients who were 18 years of age or older with histological or cytological evidence of advanced/metastatic pancreatic cancer and an ECOG performance status of 0 or 1. Moreover, patients needed to have a life expectancy of 3 months or more with no malignancies that would interfere with the study intervention. Additional inclusion criteria included having at least 1 measurable lesion and adequate baseline organ function.

Those who had known brain metastases; underwent major surgery within 4 weeks of starting treatment with PBP1510; or had active, uncontrolled bacterial, viral, or fungal infections needing systemic treatment were not eligible for enrollment. Additionally, a known history of immunodeficiency virus, a history of or active hepatitis B/C or syphilis infection, or impaired cardiac infection were also grounds for exclusion.

Other exclusion criteria included serious psychiatric disorders, any other malignancies in which the patient was disease free for less than 5 years, enrollment on another clinical trial, or treatment with radiation within 4 weeks or investigational anti-cancer agents within 28 days. Those with a known allergy or hypersensitivity to the components of PBP1510 or gemcitabine, or those who were pregnant or breast feeding were also not eligible to enroll.

Reference

Prestige Biopharma Receives FDA Fast Track Designation for PBP1510 in the Treatment of Pancreatic Cancer. News Release. Prestige Biopharma. March 21, 2023. Accessed April 3, 2023. bit.ly/431UCRI