LOAd703 Receives FDA Fast Track Designation for Pancreatic Cancer

The decision follows safety data from the phase 1/2 LOKON001 trial evaluating LOAd703 in advanced pancreatic ductal adenocarcinoma.

The FDA has granted oncolytic adenovirus LOAd703 fast track designation as a treatment for patients with pancreatic cancer, according to a news release from the drug’s developer, Lokon Pharma.¹

The decision follows data from the phase 1/2 LOKON001 trial (NCT02705196), which evaluated the therapy in combination with nab-paclitaxel and gemcitabine with or without atezolizumab (Tecentriq). Results include only the 3-drug regimen, with the 4-drug regimen arm ongoing.

Data from the trial reveal that no dose-limiting toxicities (DLTs) were reported at dose 1 (5x10¹⁰ particles per injection; n = 3) or dose 2 (1x10¹¹ particles per injection; n = 4). For dose 3 (5 x 10¹¹ particles per injection, n = 14), 1 patient had a DLT consisting of brief grade 3 alanine aminotransferase after injection of LOAd703 into a liver metastasis.² This patient received on-protocol treatment at a lower dose without additional reported DLTs. Additionally, only 11 patients of 14 assigned to dose 3 were evaluable for DLTs, as 2 experienced clinical progression prior to a third injection, and another withdrew consent.

"We are excited to share the news that LOAd703 has been granted fast track designation by the FDA,” Åsa Holmgren, MScPhm, head of Regulatory Affairs at Lokon Pharma, said in the news release.¹ “Lokon will now benefit from more frequent interactions with the FDA and if relevant criteria are met, LOAd703 may be eligible for additional expedited programs offered by the FDA to make LOAd703 available to patients as soon as possible."

Between December 2, 2016, and October 17, 2019, 23 patients were assessed for eligibility on the trial, including 22 who enrolled on trial. A total of 21 patients received at least 1 dose of LOAd703 and were evaluable for safety.

Among the 21 patients evaluable for safety, the median age was 61 years (IQR, 55-63), 13 patients were male (62%), and 3 (14%) had previously undergone resection of their primary pancreatic ductal adenocarcinoma. Furthermore, 17 (81%) patients had radiographically- or biopsy-confirmed metastases, and 10 (48%) had previous chemotherapy exposure for advanced disease.

Patients received 125 mg/m² of intravenous paclitaxel plus 1000 mg/m² of intravenous gemcitabine on days 1, 8, and 15 of a 28-day cycle for a maximum of 12 cycles. Furthermore, starting day 15 of cycle 1, 500 μL of LOAd703 was injected endoscopically or percutaneously into the tumor or metastasis every 2 weeks for 6 injections. Lesion selection was influenced by the number of lesions, accessibility, and patients’ preference. The same lesion was injected until it could no longer be visualized or accessed, and another lesion was selected for the remaining scheduled injections.

The primary end points of the trial were safety and the maximum tolerated dose of LOAd703 combined with nab-paclitaxel plus gemcitabine and antitumor immune response based on the emergence of circulating antiadenoviral antibodies,adenovirus-specific T cells, and effector memory T cells. Secondary end points included antitumor activity broken down into objective response rate and overall survival.

The most common grade 3 or 4 adverse events (AEs) included anemia (48%), neutropenia (48%), lymphopenia (43%), and leukopenia (33%), which were all attributable to chemotherapy or underlying malignancy. The most common AEs related to LOAd703 included fever (67%), fatigue (38%), chills (33%), and elevated alanine aminotransferase (24%). The most common serious AEs included fever (29%), sepsis (19%), anemia (14%), limb oedema (14%), and lower gastrointestinal bleeding (14%).

References

1. Lokon Pharma receives FDA fast track designation for LOAd703 for the treatment of pancreatic cancer. News release. Lokon Pharma. January 10, 2025. Accessed January 13, 2025. https://tinyurl.com/2apk4tew
2. Musher BL, Rowinsky EK, Smaglo BG, et al. LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study. Lancet Oncol. 2024;25(4):488-500. doi:10.1016/S1470-2045(24)00079-2