PAT-SM6 Phase I/IIa Trial Progresses To Final Cohort On Positive Data
Patrys has released additional clinical data for six multiple myeloma (MM) patients treated with PAT-SM6 in the Phase I/IIa trial. The six patients were involved in the second and third cohorts of the ongoing trial (three in each cohort), and their positive clinical outcomes supported the trial progressing to its fourth and final patient cohort. Recruitment of these patients is currently under way.
The six individuals (five male and one female aged 65 to 75 years) had end-stage, multi-resistant MM. On average, they had received five prior lines of therapy including autologous stem cell transplantation and other novel marketed compounds, including bortezomib and lenalidomide. Patrys noted that therapeutic options for such patients are usually limited to clinical trials and their median overall survival is approximately nine months.
Each patient in the second cohort received four doses of PAT-SM6 (each dose at 1mg/kg/dose) given intravenously, over a two-week period as per the protocol. Patients in the third cohort received four doses at 3mg/kg/dose. All patients were then followed up for 36 days.
All six of the patients treated in these cohorts tolerated PAT-SM6 very well. There were no drug-related serious adverse events and no dose-limiting toxicities. On the basis of these safety data, the independent Drug Safety Monitoring Board gave approval for the fourth and final cohort to commence. Patients in this final cohort will receive a minimum of four doses of PAT-SM6, each dose at 6mg/kg/dose. This is more in line with dosing levels of other antibodies currently on the market.
Of these six patients treated with PAT-SM6, two have shown stable disease. The first of these (from the second cohort) was a 73-year-old male who had previously received six lines of therapy, including a stem cell transplant. At the time of entry into the trial he was resistant to all available therapies and had rapidly advancing disease. At day +36 after treatment with four doses of PAT-SM6, he showed evidence of stable disease according to the International Myeloma Working Group criteria.
The second responder was a 75-year-old male (from the third cohort) who had previously received four lines of therapy and showed significant progression of his disease. Like the first responder, this individual showed evidence of stable disease after treatment with PAT-SM6 and currently (at the time of reporting, day +82 post-treatment) his disease remains stable and he has not gone on to receive any other treatment.
Post-inclusion in the trial, five out of six patients went on to receive additional chemotherapy due to advancing disease. Interestingly, two out of those five patients responded very positively to drugs that they had previously been resistant to. This suggests that PAT-SM6 is having a positive influence on the cancer cells by converting them from resistant to sensitive. Overall, there was a median time-to-next therapy of 42 days, which Patrys noted is considered to be clinically significant.
As part of the overall assessment of these treated patients, the status of their immune systems was closely monitored. Of significant importance were the changes in natural killer (NK) cells. Specifically, in one of the patients who showed stable disease post-treatment with PAT-SM6, levels of NK cells were significantly increased, perhaps suggesting that these cells played a role in the control of tumour growth. Analyses of these data are currently ongoing.