FDA Grants Orphan Drug Designation to PEP-010 in Pancreatic Cancer

US FDA

• The FDA granted an orphan drug designation to PEP-010 for the treatment of patients with metastatic pancreatic cancer.
• PEP-010 is a first-in-class bi-functional therapeutic peptide.
• An ongoing first-in-human phase 1 study (NCT04733027) is currently evaluating the combination of PEP-010 with paclitaxel or gemcitabine in solid tumors.

The FDA granted PEP-010, a first-in-class bi-functional therapeutic peptide, orphan drug designation for the potential treatment of patients with metastatic pancreatic cancer.¹

A phase 1 study is currently evaluating PEP-010 in patients with advanced solid tumors ineligible for standard therapy. The study aims to determine the safety, pharmacokinetics (PK), and preliminary antitumor activity of PEP-010, both as monotherapy and in combination with paclitaxel or gemcitabine.

“Receiving the FDA’s orphan drug designation is an important milestone for PEP-Therapy,” Antoine Prestat, chief executive officer and co-founder of PEP-Therapy, said in the press release.¹ “It will support our objective to accelerate the development of PEP-010 toward delivering an innovative solution for challenging-to-treat cancers. We look forward to reporting updated clinical data.”

In the monotherapy arm (arm A; n = 19) of the phase 1 study, patients received PEP-010 as 3-hour intravenous weekly infusions on 3 consecutive days across 8 dose levels (0.15 mg/kg to 15 mg/kg), demonstrating an acceptable safety profile. One patient experienced a grade 2 infusion-related reaction (IRR) at the highest dose and stable disease was observed in 7 patients with a median duration of 2.8 months.²

In the combination arm with paclitaxel (arm B; n=15), dose-limiting toxicities (DLTs), including grade 4 neutropenia and grade 2/4 IRRs, were observed at a PEP-010 dose of 5 mg/kg, limiting further dose escalation. Notably, 4 patients in this arm achieved confirmed partial responses (PRs) in ovarian, pancreatic, thyroid adenocarcinomas and squamous cell lung carcinoma. Stable disease was observed in 2 patients with a median of 4 months.

Microscopic image of pancreatic cancer cells - Generated with Google Gemini AI

The primary end point of the trial was to determine the maximum tolerated dose and the recommended phase 2 dose of PEP-010 in both arms. This was based on the occurrence of dose-limiting toxicities. The secondary end points of the study were the safety and tolerability profile, pharmacokinetics (PK), and preliminary antitumor activity assessed by RECIST1.1.

Overall, the most common PEP-010-related adverse events (AEs) were asthenia (26.5%) and IRRs (14.7%), while paclitaxel-related AEs included anemia (66.7%), peripheral neuropathy (33.3%), and neutropenia, onychopathy, and diarrhea (20.0% each).

PK data showed dose-proportional increases in PEP-010 systemic exposure without accumulation or interaction with paclitaxel.

The observed preliminary antitumor activity warrants further investigation. Future studies will focus on optimizing dosing and further characterizing efficacy in combination with paclitaxel and gemcitabine.

References

1. PEP-Therapy receives FDA orphan drug designation for PEP-010 for treatment of pancreatic cancer. News release. PEP-Therapy. March 17, 2025. Accessed March 20, 2025. https://tinyurl.com/yt3n89nt

2. du Rusquec P, Coquan E, Berger F, et al. A first-in-human phase 1a/b of PEP-010, a single proapoptotic bifunctional peptide, administered as single agent and in combination with paclitaxel in patients with recurrent and/or metastatic solid cancer: Results from the dose escalation. Mol Cancer Ther. 2023;22(suppl 12):B046. doi:10.1158/1535-7163.TARG-23-B046