PEP-010 Wins FDA Orphan Drug Designation in Metastatic Pancreatic Cancer

FDA

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

PEP-010 is currently being evaluated in combination with paclitaxel or gemcitabine in an ongoing first-in-human phase 1 study (NCT04733027) to assess safety, pharmacokinetics, and preliminary antitumor activity per RECIST 1.1 criteria.1,2 Data from the escalation portion of the study has shown an acceptable safety profile of PEP-010 in monotherapy.2 However, in the combination, the dose of PEP-010 could not be escalated to the same level as the monotherapy because of infusion-related reactions (IRRs).

At a data cutoff of March 7, 2023, patients in arm A (n = 19) were treated with PEP-010 monotherapy, and patients in arm B (n = 15) were treated with PEP-010 plus paclitaxel with 8 and 3 dose levels in the respective arms. In arm A, 1 patient experienced a grade 2 IRR at dose level 8, which was PEP-010 at 15 mg/kg. In arm B, 3 patients reported dose-limiting toxicities with PEP-010 at 5 mg/kg, which included 1 grade 4 neutropenia and 2 unacceptable grade 2 and 4 IRRs, respectively. Notably, these dose-limiting toxicities in both arms led to permanent treatment discontinuation.

In the overall population, the most common adverse effects (AEs) related to PEP-010 were asthenia (26.5%) and IRR (14.7%); the most common AEs related to paclitaxel were anemia (66.7%), peripheral neuropathy (33.3%), neutropenia, onychopathy, and diarrhea (20.0% each). In arm A, the median time on treatment was 5.1 weeks (range, 2.1-25.3) and 5.3 weeks (range, 3-18) in arm B.

“Obtaining orphan drug designation for PEP-010 marks a significant milestone in our efforts to develop our drug candidate for pancreatic cancer and highlights the significant unmet medical need that exists for these patients,” Hatem Azim, MD, PhD, chief medical officer of PEP-Therapy, stated in a news release.1 “They currently have limited treatment options, and the growing incidence and mortality of pancreatic cancer underscores the urgency for new therapies. Orphan drug designation along with encouraging initial data from our ongoing phase 1 study strengthen the advancement of PEP-010 as a potential novel alternative.”

PEP-010 penetrates cells and targets the interaction between Caspase9 and PP2A involved in the apoptotic cascade, which leads to Caspase9-dependent apoptosis in cancer cells.

In both arms of the study, PEP-010 was administered intravenously for 3 hours for 3 consecutive days in patients with advanced cancer ineligible for standard therapy.2 Patients in arm A were enrolled into 8 dose cohorts to receive PEP-010 starting at 0.15 mg/kg to 15 mg/kg via an accelerated titration design for the first 4 dose levels, followed by a 3+3 design. Patients in arm B were treated with 5 dose levels of PEP-010 plus weekly paclitaxel at 80 mg/m2.

In the phase 1a portion of the study, the primary objective of the study was to determine the maximum tolerated dose of PEP-010 and to identify the recommended phase 2 dose in both arms, based on the occurrence of dose-limiting toxicities.

Regarding preliminary efficacy data, stable disease (SD) was observed at a median of 2.8 months (range, 0.6-4.5) in 7 patients from arm A.2 Of note, confirmed partial responses were observed in 4 patients from arm B with ovarian, pancreatic, and thyroid adenocarcinomas and squamous cell lung carcinoma. At a median of 4 months (range, 2.7-9.6), 2 patients from arm B had SD. Pharmacokinetic data indicated a proportionally dose-related increase in systemic exposure to PEP-010. However, no accumulation of PEP-010 was observed over time or impact of the PEP-010/paclitaxel combination.

“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, added in the news 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.”

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://www.globenewswire.com/news-release/2025/03/17/3043732/0/en/PEP-Therapy-receives-FDA-Orphan-Drug-Designation-for-PEP-010-for-treatment-of-Pancreatic-Cancer.html
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