Several patients progressed with their cancer disease despite treatment and eventually they become refractory. We selected patients from several malignancies with PD despite standard of care treatment (n = 30) and performed a pilot clinical study to evaluate the effect of two intravenously, two oral and one subcutaneously agent. With this in mind and with a systematic review and immunomodulatory, anti-angiogenic and anti-tumoral validation of each drug was studied. We tested the preexisting CD8 and Th1 antigen specific immune response against several clinically relevant peptides from bad prognosis proteins.
30 subjects were included after the CICS ethics committee approved the protocol. The inclusion criteria include ECOG=0, complete CT scan from neck, thorax, abdomen and pelvis, laboratory tests such as CBC, phase acute proteins, etc. The patients were accepted after initial IFN-gamma and Elispot assays were done to make sure we have only patients with Th1 and CD8 immune response, as we know that ipilimumab unleashes every T cell. The tumors included were PDAC (n = 5), HGSOC (n = 12), TNBC (n = 10) and MM (3). The patients received the oral and the IV treatment biweekly for 4 months.
We had 60% of CR and 40% of PR. The tumor with more significant response was ovarian (90%). There was an immunological correlation of CD8 immune response between in both CR (p = 0.001) and PR (p = 0.05). The combination was well tolerated and after 16 months of stopping the treatment some patients have persistent CD8 antigen specific immune response.
The combination is clinically feasible, looks promising and we now understand the importance of preserving the immune response and the use of biomarkers to improve the rational and generate new combinations with this approach to improve clinical outcomes.
Clinical trial identification
DOES NOT APPLY
Legal entity responsible for the study
CENTRO DE INVESTIGACION DE CANCER EN SONORA CAMPUS CIUDAD OBREGON, SONORA, MEXICO
Fundacion del centro de investigacion de cancer en sonora (cics) campus ciudad obregon, sonora, Mexico.
All authors have declared no conflicts of interest.