The results from the first part of the PLIANT study show that PledOx was well tolerated by patients treated with FOLFOX chemotherapy.
Treatment with FOLFOX often causes severe painful sensory disorders known as neuropathies. These severe side-effects did not occur in patients who were pre-treated with PledOx, a compound that among other properties prevents severe side-effects of chemotherapy in cancer treatment. The lower dose of PledOx also indicated a reduction of serious white blood cell-related side effects.
The raw data from the dose-escalation part have now been compiled in a preliminary analysis. One can observe that, unlike during normal FOLFOX treatment of colorectal cancer, no moderate or serious neuropathies (grade 2 or higher) were observed despite up to 8 cycles of FOLFOX. This was seen for both doses of PledOx. The expected outcome without PledOx-treatment is that approximately 30% of the patients will develop neuropathies of grade 2 or worse after 8 cycles.
“What impresses most on the oncologists that we have talked to was the fact that PledOx seems to reduce the risk of chemotherapy induced sensory nerve disorders known as neuropathies. The reason for this being that chemotherapy induced neuropathy is a major clinical problem and the main reason for discontinuing oxaliplatin-based chemotherapy” says CEO Jacques Näsström.
In addition, it seems that the low dose in particular appears to have the potential to reduce serious (grade 3) white blood-related side effects such as decrease in neutrophils. Neutrophils are an essential type of white blood cells in defending the body against bacterial infections.
According to these data, the lower dose of PledOx will give the best effect. PledPharma has therefore applied to the regulatory authorities for reduction of the higher dose of 10μmol/kg to 5 μmol/ kg. The reduction is primarily based on the apparent better effect on white blood cell-related side effects with the lower dose of PledOx.
So far the new dose is approved in Sweden and in the U.S.
This change in dose also means that the full number (i.e. 42) randomized patients must be included in order to be able to statistically evaluate the new dose, which will result in an expansion of the study and an extension of the trial period. Patients treated with the new dose will, however, replace the majority of patients that should have be treated with the higher dose of 10 μmol/kg since the dose change occurs early on in the study.
The current estimate is that all patients should be included in the study before the end of 2014 and that overall (top-line) data should be available towards the end of the first quarter of 2015.
Currently, all six patients in the dose escalation part have completed their treatment. Furthermore, all patients being treated with FOLFOX in combination with bevacizumab have started their treatment and DSMB has now given its initial approval to continue the treatment with bevacizumab in combination with FOLFOX. In addition, three patients are included in the second part of the study (the randomized part) and at the high end of 20 centers are actively recruiting patients to the study and these centers have identified an additional handful of candidates to include in the study.