Advaxis Inc., a clinical-stage biotechnology company developing cancer immunotherapies, announced that the Georgia Regents University (GRU) Cancer Center has received Institutional Review Board (IRB) approval to initiate a Phase 1/2 trial evaluating higher doses and repeat cycles of ADXS-HPV in patients with recurrent cervical cancer. The trial will be conducted at GRU under the direction of Dr. Samir Khleif, director, GRU Cancer Center. ADXS-HPV is Advaxis’s lead Lm-LLO cancer immunotherapy product candidate, designed to target HPV-associated cancers. 

 

This Phase 1/2 study is designed to evaluate the safety, efficacy and immunological effect of the highest-tolerated dose of ADXS-HPV administered in repeat cycles of treatment to patients with cervical cancer whose disease recurred after receiving one prior cytotoxic treatment regimen. Advaxis’s earlier Phase 2 clinical study in 110 women with recurrent cervical cancer had already demonstrated that a single cycle (three doses) of ADXS-HPV at a dose of 1×109 colony forming units (CFU) is well-tolerated with complete and partial tumor responses as well as an apparent survival benefit. Building on this data, among the purposes of this study is to evaluate the effect of repeat cycles of treatment (multiple doses) of ADXS-HPV at higher doses. 

 

Higher doses, equivalent to 1×1010 CFU, along with multiple cycles of treatment have been administered to pet dogs with naturally occurring canine osteosarcoma and preliminary results from the on-going clinical trial show statistically significant overall survival with only minor side effects. In addition, laboratory experiments clearly show improved activity against cancer when ADXS-HPV is given at higher doses and in repeat cycles of treatment. Advaxis believes that repeat cycles of treatment at higher doses may further improve the positive clinical benefits already observed in its prior Phase 2 study. 

 

Dr. Robert Petit, chief scientific officer of Advaxis, commented, “We have already seen safety and efficacy data from a single cycle of ADXS-HPV at the low dose of 1×109 CFU. We hope to improve on the clinical outcomes seen in our Phase 2 trial by using a higher dose and repeat cycles of treatment. This high-dose Phase 1/2 clinical study will run in parallel with our planned pivotal Phase 3 registration program for ADXS-HPV in patients with cervical cancer.” 

 

Petit further stated, “The 100-1000 fold greater attenuation of the Advaxis vector coupled with the higher secretion of the tumor antigen per CFU, should pair together to significantly amplify signaling of the immune system and result in a greater number of cancer fighting T cells. Recurrent cervical cancer is a fatal disease and is resistant to treatment. These women deserve the strongest treatment effect we can generate, in an attempt to prolong their survival.” 

 

The final results from Advaxis’s prior Phase 2 study were recently reported at the 2014 American Society of Clinical Oncology Annual Meeting, and showed that 22% (24/109) of the patients were long-term survivors (>18 months). 18% (16/91) of patients were alive for more than 24 months. In this Phase 2 study, 32% (35/109) of patients were alive at 12-months and a tumor response rate was observed in 11% (including complete responses and partial responses) of patients with a median duration of response of 9.5 months. A disease control rate (>three months) was observed in 38% (42/109) of patients. These results were achieved with the lowest dose of ADXS-HPV that was tested in Phase 1, and at this dose 68% of the patients did not report any ADXS-HPV related effects. The remainder patients experienced only low grade (1-2) transient effects the day of dosing. One patient had a grade 3 fever that responded to treatment with acetaminophen (Tylenol).

 

Date: June 16, 2014

Source: Advaxis