The FDA has granted Fast Track designation to LOAd703, an oncolytic adenovirus developed by Lokon Pharma, for the treatment of patients with pancreatic cancer. This designation aims to expedite the development and review of drugs that show potential in addressing unmet medical needs for serious conditions.
The decision follows promising data from the phase 1/2 LOKON001 trial (NCT02705196), which is evaluating LOAd703 in combination with nab-paclitaxel and gemcitabine, with or without atezolizumab, for patients with unresectable or metastatic advanced pancreatic ductal adenocarcinoma (PDAC). The initial data focuses on the three-drug regimen, while the four-drug regimen arm is ongoing.
Clinical Trial Data
Data from the LOKON001 trial, published in The Lancet Oncology, revealed encouraging results. Among the 18 patients evaluable for activity in arm 1, the overall response rate (ORR) was 44% (95% CI, 25%-66%), and the disease control rate (DCR) was 94% (95% CI, 74%-99%). No complete responses were observed. Specifically, in the 11 patients who received dose level 3, the ORR was 55% (95% CI, 28%-79%) and the DCR was 91% (95% CI, 62%-98%).
The median overall survival (OS) for efficacy-evaluable patients was 9.3 months (95% CI, 6.2-13.6), with a median progression-free survival (PFS) of 5.4 months (95% CI, 4.0-7.5). The OS rate at 12 months was 35% (95% CI, 14%-57%). In the safety population (n = 21), the median OS was 8.7 months (95% CI, 6.0-12.7). As of the data cutoff date of January 5, 2023, all patients with known survival status had died due to disease progression.
Safety Profile
In terms of safety, no dose-limiting toxicities (DLTs) were reported at dose levels 1 (5x10^10 particles per injection; n = 3) or 2 (1x10^11 particles per injection; n = 4). At dose level 3 (5 x 10^11 particles per injection, n = 14), one patient experienced a DLT consisting of a brief grade 3 alanine aminotransferase elevation after LOAd703 injection into a liver metastasis. This patient continued treatment at a lower dose without further DLTs.
The most common adverse events (AEs) related to LOAd703 included fever (67%), fatigue (38%), chills (33%), and elevated alanine aminotransferase (24%). All AEs related to LOAd703 were grade 1 or 2, except for the single transient grade 3 elevation in aminotransferase levels observed at dose level 3. No patients discontinued treatment or experienced fatal adverse events related to LOAd703. The maximum tolerated dose was not identified, with dose level 3 determined as the highest safe dose when LOAd703 was combined with gemcitabine and nab-paclitaxel.
Mechanism of Action
LOAd703 is an oncolytic adenovirus engineered with transgenes encoding 4-1BBL and TMZ-CD40L. Preclinical models have demonstrated that this immunostimulatory gene therapy selectively lyses cancer cells, activates cytotoxic T cells, and induces tumor regression.
Implications of Fast Track Designation
Åsa Holmgren, MScPhm, head of Regulatory Affairs at Lokon Pharma, stated that the Fast Track designation will allow Lokon Pharma to benefit from more frequent interactions with the FDA. If relevant criteria are met, LOAd703 may be eligible for additional expedited programs offered by the FDA to make the therapy available to patients as soon as possible.
Lokon Pharma is also evaluating LOAd703 in combination with gemcitabine and nab-paclitaxel plus an anti-PD-L1 antibody in pancreatic cancer, with a randomized phase 2 study planned.
