CLINICAL TRIALS
The immune system is a key line of defense against tumors, and multiple molecular transformations have to occur for tumors to be tolerated. Once this happens, potent vaccines are required to break tolerance. Aduro has taken Listeria monocytogenes (Listeria), which is able to induce potent and broad immune responses, and rendered the bacteria safe for human use while enabling genetic targeting against specific molecules found in tumors.
CRS-207 is Aduro’s lead Listeria-based therapeutic and has been engineered to express the tumor-associated antigen mesothelin. CRS-207 was evaluated in a Phase 1 trial in 17 end-stage patients with cancers known to express mesothelin: mesothelioma, non-small-cell lung, ovarian and pancreatic. Analysis after the completion of the trial revealed a mesothelin-specific T cell response in multiple patients and, despite an expected survival of 3-5 months for all subjects, six out of 17 lived 15 months or longer.
GVAX cancer vaccines are based on human cancer cell lines that are genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune-stimulatory cytokine. GVAX Pancreas has been evaluated in more than 120 patients and shown to be well tolerated and able to induce mesothelin-specific T cell responses.
Sequential administration of GVAX Pancreas followed by CRS-207 was first shown by Aduro to be synergistic in mouse models, demonstrating enhanced tumor-specific T cell and anti-tumor responses. Because both GVAX Pancreas and CRS-207 target the tumor-associated antigen mesothelin, the sequential administration is a heterologous prime-boost regimen. Listeria is known to be especially effective in this regimen.
Based on the synergy in preclinical animal models, Drs. Elizabeth Jaffee and Dung Le of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins included three pancreatic cancer patients in the CRS-207 Phase 1 clinical trial who had previously received GVAX Pancreas as part of separate clinical trials. All three late-stage patients who received sequential therapy lived 15 months or longer.
Aduro is planning a Phase 2 trial of the sequential administration of GVAX Pancreas and CRS-207. The trial will take place at multiple academic centers across the U.S. and is expected to initiate in the fourth quarter of 2011 and enroll a total of 90 late-stage pancreatic cancer patients. For more information, please see the listing at clinicaltrials.gov.
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