FDA Grants Fast Track Designation to PBP1510 in Metastatic Pancreatic Adenocarcinoma

FDA

The FDA has 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 targets the tumor-specific protein PDAC upregulated factor (PAUF), which is overexpressed in most patients with pancreatic cancer. PAUF overexpression promotes key cellular functions, including proliferation, migration, invasion, and growth of pancreatic cancer cells, and is linked to acquired resistance to chemotherapeutic agents.

Preclinical models have shown that PBP1510 effectively inhibited the tumorigenic effects of PAUF overexpression. The agent will be investigated in a first-in-human phase 1/2a trial (NCT05141149) as monotherapy and in combination with gemcitabine.

The open-label, dose-escalation and dose-expansion, multicenter, two-part study will enroll patients at least 18 years of age with histologically or cytologically confirmed advanced/metastatic pancreatic cancer whose tumor has progressed on 1 previous line of chemotherapy for locally advanced/metastatic disease.2 Patients will be required to 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.

Prior radiation is allowed to 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.

Key exclusion criteria include known brain metastases, major surgery within 4 weeks of the first dose of PBP1510, and treatment with any investigational anticancer drug within 4 weeks of enrollment.

Part 1 of the trial will consist of dose escalation with PBP1510 monotherapy and dose escalation in combination with gemcitabine. Part 2 will feature dose expansion 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, where patients will receive the same doses of PBP1510 in combination with gemcitabine.

The primary end points in part 1 will be to evaluate the safety and tolerability of PBP1510 and identify any dose-limiting toxicities. The primary end points in part 2 will consist of assessing the safety and efficacy of PBP1510 in combination with gemcitabine. Key secondary end points for part 1 include determining the RP2D of PBP1510 and pharmacokinetics.

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 March 31, 2023. https://www.preipopharma.com/press-releases/
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 March 31, 2023. https://clinicaltrials.gov/ct2/show/NCT05141149