Date: 2013-12-27
Type of information:
phase: 2
Announcement: results
Company: Axelar (Sweden)
Product: AXL1717
Action mechanism: AXL1717 - picropodophyllin is a targeted oral small-molecule insulin-like growth factor 1 (IGF-1) receptor pathway inhibitor with no observable effect on the closely related insulin receptor. Most tumor cells are dependent on the IGF-1 receptor signal pathway and the IGF-1 receptor is therefore regarded as a promising target for cancer therapy. To date, there are no IGF-1 receptor inhibitor drugs on the market.
Disease: non small cell lung cancer (NSLC)
Therapeutic area: Cancer - Oncology
Country:
Trial details: The study is a randomized open-label Phase II clinical study that compares AXL1717 with conventional cytotoxic chemotherapy (docetaxel) in patients with previously treated, locally advanced or metastatic NSCLC. The clinical study is conducted at 25 centers in five countries and has rate of progression free survival (PFS) after 12 weeks as the primary endpoint. Preliminary analysis suggests that AXL1717 has similar rate of PFS after 12 weeks as docetaxel. The most frequent serious adverse events in the study were cases with neutropenia, which occurred in both treatment regimes.
Latest
news: * On December 27, 2013, Axelar has announced the final results from its Phase II study AXL-003 in patients with non-small cell lung cancer (NSCLC). The final data showed no statistically significant difference in rate of progression-free survival (PFS) between the patients treated with AXL1717 compared with the group treated with docetaxel, which confirms the previously communicated preliminary data. “Although we did not see an improved outcome for the patients with NSCLC that received AXL1717 compared to patients receiving docetaxel, we are still encouraged by the results from AXL-003. The clinical data taken together with new data on a second mechanism of action suggest that AXL1717 has the potential to be developed for patients that have relapsed after treatment with docetaxel in this difficult to treat indication”, says Mikael von Euler, CEO of Axelar. In addition to the IGF-1R pathway inhibition, AXL1717 also seems able to suppress tumor cell division by arresting cells in mitosis through a non-IGF-1R dependent mechanism. A total of 101 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC, stage IIIB or IV) were randomized in the AXL-003 study (see ‘About AXL-003’). The primary objective was to compare the rate of progression-free survival (PFS) at 12 weeks between the group of patients treated with AXL1717 and the docetaxel group. The 12-week PFS rate for the 99 patients who received study medication was 25.9% in the AXL1717 group and 39.0% in the docetaxel group, the difference was not statistically significant (p=0.19). The overall survival results for patients with adenocarcinoma suggested a more favorable outcome following treatment with AXL1717 compared with the outcome for patients with squamous cell carcinoma. Axelar is planning to present more data from AXL-003 at scientific meetings during 2014. * On April 2, 2013, Axelar has announced that preliminary interim results of its Phase II study AXL-003, indicates that AXL1717 is effective in treating patients with non-small cell lung cancer (NSCLC). Preliminary analysis suggests that AXL1717 has similar rate of PFS after 12 weeks as docetaxel. The most frequent serious adverse events in the study were cases with neutropenia, which occurred in both treatment regimes. Based on the interim data from AXL-003, Axelar has decided to finalize the trial with approximately 100 patients instead of the planned 140. As of today, 97 patients have been enrolled in the trial and these patients will continue to be treated and monitored according to the study protocol. More detailed data from the study, including secondary read-outs and safety, will be presented at a coming scientific meeting. Thus, the company assesses that it has sufficient data to guide further development of the drug, and will finalize the study with fewer patients than initially planned.
* On December 28, 2011, Axelar has announced that the first patient has been dosed in a randomized Phase II study on non-small cell lung cancer patients of AXL1717. In the recently completed Phase I/II study, AXL1717 demonstrated a good safety profile and signs that suggest clinical benefit were observed in some patients with NSCLC.
