Immutep Announces Final Results In Phase I/II Chemoimmunotherapy Trial in Breast Cancer
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Immutep S.A. has announced the final results from its Phase I/II chemoimmunotherapy clinical trial in metastatic breast carcinoma. The final results confirm the clinical response rate of 50 percent using Immutep's IMP321 associated with paclitaxel. This compares to 25 percent using paclitaxel alone.
ImmuFact® IMP321 is a T cell immunostimulatory agent. Repeated IMP321 injections lead to strong anti-tumour T cell responses. In synergistic combination with chemotherapy, IMP321 doubles the clinical response rate. This therapeutic strategy is called 'chemo-immunotherapy'.
Chemo-immunotherapy is a new approach to the treatment of cancer. Chemotherapy drugs induce tumour cell apoptosis and cause modulation of the immunological environment combined with a burst of tumour antigen release. The resulting T cell immune response contributes to the regression of the tumour. However, this initial immune response needs to be sustained and amplified by a CD8 T-cell booster that is non-toxic and can be given repeatedly, such as ImmuFact IMP321.
The study was a multi-centre open-label fixed dose-escalation trial. Patients received 6 cycles of weekly paclitaxel, 3 weeks out of 4, as first line chemotherapy, plus bi-weekly IMP321 administered the day after the paclitaxel to make a total of 12 injections of IMP321 over 24 weeks. Three dose levels of IMP321 were studied. The results are based on tumour regression under RECIST criteria in 30 patients compared to the historical control group which is the weekly paclitaxel arm of a recent randomized phase III study. The improvement is highly statistically significant with a p-value of 0.004.
In addition, immuno-monitoring confirmed that IMP321 is a potent agonist of the anti-cancer cellular immune response. Major components of the immune response (monocytes, dendritic cells and the vital CD8 memory T cells) were found to be expanded/activated for several months.
Further evidence of the mechanism of action came from the analysis of tumour regression during the second three months compared to the first three months. Under chemo alone, most tumour regression takes place during the early period and less during the later period. Using IMP321, however, investigators observed enhanced tumour regression in the later period as well; late responses are characteristic of a cancer immunotherapy effect.
"With such chemo- and non-toxic immunotherapeutic combinations, we have been able to improve the response rate and/or consolidate or stabilize the partial tumour responses obtained with chemotherapy alone," said Dr Maya Gutierrez, Principal Investigator, René Huguenin Cancer Centre.
"These final results based on 30 patients treated and a p-value of 0.004 mean that we have the results required to go forward to a pivotal trial," said Frédéric Triebel, Scientific & Medical Director of Immutep. "This form of chemo-immunotherapy should be applicable to many chemotherapies. For example, it is now being tested in the USA in association with gemcitabine in pancreatic cancer."
"The next steps are a Phase IIb pivotal trial leading to Conditional Marketing Authorization in Europe and further trials in other cancers and with other chemotherapies. Partnering discussions are in progress," added John Hawken, CEO.
ImmuFact® IMP321 is a T cell immunostimulatory agent. Repeated IMP321 injections lead to strong anti-tumour T cell responses. In synergistic combination with chemotherapy, IMP321 doubles the clinical response rate. This therapeutic strategy is called 'chemo-immunotherapy'.
Chemo-immunotherapy is a new approach to the treatment of cancer. Chemotherapy drugs induce tumour cell apoptosis and cause modulation of the immunological environment combined with a burst of tumour antigen release. The resulting T cell immune response contributes to the regression of the tumour. However, this initial immune response needs to be sustained and amplified by a CD8 T-cell booster that is non-toxic and can be given repeatedly, such as ImmuFact IMP321.
The study was a multi-centre open-label fixed dose-escalation trial. Patients received 6 cycles of weekly paclitaxel, 3 weeks out of 4, as first line chemotherapy, plus bi-weekly IMP321 administered the day after the paclitaxel to make a total of 12 injections of IMP321 over 24 weeks. Three dose levels of IMP321 were studied. The results are based on tumour regression under RECIST criteria in 30 patients compared to the historical control group which is the weekly paclitaxel arm of a recent randomized phase III study. The improvement is highly statistically significant with a p-value of 0.004.
In addition, immuno-monitoring confirmed that IMP321 is a potent agonist of the anti-cancer cellular immune response. Major components of the immune response (monocytes, dendritic cells and the vital CD8 memory T cells) were found to be expanded/activated for several months.
Further evidence of the mechanism of action came from the analysis of tumour regression during the second three months compared to the first three months. Under chemo alone, most tumour regression takes place during the early period and less during the later period. Using IMP321, however, investigators observed enhanced tumour regression in the later period as well; late responses are characteristic of a cancer immunotherapy effect.
"With such chemo- and non-toxic immunotherapeutic combinations, we have been able to improve the response rate and/or consolidate or stabilize the partial tumour responses obtained with chemotherapy alone," said Dr Maya Gutierrez, Principal Investigator, René Huguenin Cancer Centre.
"These final results based on 30 patients treated and a p-value of 0.004 mean that we have the results required to go forward to a pivotal trial," said Frédéric Triebel, Scientific & Medical Director of Immutep. "This form of chemo-immunotherapy should be applicable to many chemotherapies. For example, it is now being tested in the USA in association with gemcitabine in pancreatic cancer."
"The next steps are a Phase IIb pivotal trial leading to Conditional Marketing Authorization in Europe and further trials in other cancers and with other chemotherapies. Partnering discussions are in progress," added John Hawken, CEO.
