FDA Grants FTD to PBP1510 for Unresectable/Metastatic Pancreatic Adenocarcinoma

The FDA granted a fast track designation to PBP1510 (ulenistamab) for the treatment of patients with unresectable or metastatic pancreatic adenocarcinoma (PDAC) that has relapsed following and/or is refractory to at least 1 prior line therapy.¹

PBP1510 is a novel humanized IgG1 monoclonal antibody which targets the tumor-specific protein PDAC upregulated factor (PAUF), which is overexpressed in most patients with pancreatic cancer. The overexpression of PAUF leads to key cellular functions, including proliferation, migration, invasion, and growth of pancreatic cancer cells, and is linked to acquired resistance to chemotherapeutic agents.

In preclinical models, PBP1510 inhibited the tumorigenic effects of PAUF overexpression. Now, the agent is being investigated in a first-in-human phase 1/2a trial (NCT05141149).

In the open-label, dose-escalation, and dose-expansion, multicenter, 2-part study, investigators are evaluating PBP1510 as a monotherapy and in combination with gemcitabine. In part 1 of the trial, there will be a dose-escalation portion with PBP1510 monotherapy and dose escalation in combination with gemcitabine. Part 2 will then be a dose-expansion portion with PBP1510 at the recommended phase 2 dose (RP2D) in combination with gemcitabine.

In the 5 PBP1510 monotherapy cohorts, patients will receive escalating doses of the agent at 1 mg/kg, 3 mg/kg, 6 mg/kg, 10 mg/kg, and 15 mg/kg for 2 cycles. There will also be 5 combination cohorts in which patients will receive the same doses of PBP1510 in combination with gemcitabine.

Patients must be at least 18 years or older with a histologically or cytologically confirmed diagnosis of advanced/metastatic pancreatic cancer. Patients must have a tumor that has progressed on 1 prior line of chemotherapy for locally advanced/metastatic disease, have at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate baseline organ function.²

Patients were allowed to have prior radiation for the treatment of cancer that is less than 25% of the bone marrow, and patients must have recovered from the acute toxic effects of treatment prior to enrollment. Prior radiotherapy must be completed at least 4 weeks before the first dose of PBP1510.

In part 1, the primary end points of the trial will be to evaluate the safety and tolerability of PBP1510 and identify any dose-limiting toxicities. Secondary end points for this part are to determine the RP2D of PBP1510 and the pharmacokinetics. Additionally, the primary end points in part 2 will be to assess the safety and efficacy of PBP1510 in combination with gemcitabine.

REFERENCES:

1. 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.

2. First in human phase1/2a clinical trial of anti-PAUF monoclonal antibody PBP1510 in patients with pancreatic cancer. ClinicalTrials.gov. Updated February 8, 2023. Accessed April 3, 2023. https://clinicaltrials.gov/ct2/show/NCT05141149