-
Results show BNC105 utility in patients with advanced disease
-
Identified biomarkers which correlate with patient benefit (progression free survival at 6 months)
-
Addition of BNC105 to Afinitor treatment delayed disease progression in patient subgroups identified on the basis of metastases, previous nephrectomy and Fuhrman tumour differentiation grade
-
Primary endpoint showed a similar proportion of patients in both treatment arms free of progression at 6 months in the unselected patient population
ADELAIDE, Australia I March 18, 2014 I Bionomics Limited (ASX:BNO) (ADR:BMICY) today announced the results of the DISRUPTOR-1 trial of BNC105 in patients with metastatic renal cancer.
“The DISRUPTOR-1 trial has been the first of its kind in testing the combination of an mTOR inhibitor with a vascular disrupting agent in renal cancer, with the prospect of adding a new dimension to the renal cancer treatment armamentarium,” said Dr Deborah Rathjen, Bionomics’ CEO & Managing Director.
“Significant progress has been made in validating BNC105 as an anti-cancer agent. Through patient subgroup analysis and association of biomarkers to treatment benefit, the data from this trial shows us the best way forward to maximising the utility of BNC105 for renal cancer patients, as well as how to best employ the drug in other cancer types.”
“DISRUPTOR-1 has produced a ground-breaking discovery of potential biomarkers that may allow pre-treatment selection of patients most likely to benefit from BNC105.”
“We are exploring partnership opportunities for BNC105 and expect to attract a depth of interest given the compelling data generated from this trial and the recent ovarian cancer trial data,” Dr Rathjen added.
Outline of the DISRUPTOR-1 trial
Bionomics conducted this randomised Phase II clinical trial in patients with metastatic renal cell cancer with 139 patients enrolled at sites across the US, Singapore and Australia.
The trial design targeted patients who had previously failed up to two tyrosine kinase inhibitor therapies, randomising them to either of two treatment arms: one receiving the standard of care renal cancer drug Afinitor and the other receiving both Afinitor and BNC105. Patients who were progressing or who were intolerant to Afinitor monotherapy, were allowed to receive BNC105 single agent treatment. Patients were treated until disease progression or until adverse effects prohibited further therapy.
Data from a total of 136 patients (69 in the BNC105 + Afinitor arm and 67 in the Afinitor-only arm) treated in this study were able to be analysed. The combination of BNC105 and Afinitor was safe and tolerable. The adverse event profile of the combination arm did not significantly differ from that of the Afinitor-only arm, and mirrored the known and expected toxicities of Afinitor.
BNC105 combination treatment benefited patients with more advanced disease
In relation to the primary endpoint, the proportion of patients free of progression at 6 months in the unselected patient population was similar between the two arms (23 patients in the BNC105 + Afinitor arm, vs 20 patients in the Afinitor-only arm, roughly 1/3 of the patients in each arm, p=0.6625). The median Progression Free Survival (PFS) in the unselected patient population was also similar between the study arms (4.7 months in the BNC105 + Afinitor arm vs 4.1 months in the Afinitor-only arm).
An analysis of patient subgroups indicated that a 3.8 month increase in PFS favouring the BNC105 + Afinitor combination over Afinitor-only monotherapy was observed in patients with liver metastases (6.6 months vs. 2.8 months) . Metastatic lesions to the liver adversely affect prognosis, with an average 5-year survival rate of approximately 30%.
Patients with a previous nephrectomy (kidney removal) also showed a trend to improved PFS with the BNC105 + Afinitor combination than with Afinitor alone (7.1 months vs 4.1 months) with a 3 month improvement in PFS.
PFS in the BNC105 + Afinitor arm was increased by approximately 50% (from 4.1 to 6.4 months) in patients with Furhman Grade 2 histological differentiation grade. Furhman grade, based on nuclear and nucleolar morphology, is an independent prognostic factor for survival.
Taken together these results indicate that future clinical trials of BNC105 in renal cell carcinoma should be enriched for these patient subgroups.
“Defining responder patient subgroups is very important. Several drugs are now available for renal cancer patients. The latest experience suggests that we need to be more targeted in matching up the right drug with the right patient subpopulation. This need is becoming clearly evident for a number of agents currently in use in the renal cancer setting,” commented Dr Thomas E Hutson.
Dr Hutson is Director, GU Oncology, Charles A Sammons Cancer Center, Baylor University Medical Center, and Professor of Medicine, at the Texas A&M HSC College of Medicine. Dr Hutson was the global Principal Investigator for the DISRUPTOR-1 clinical trial.
“It is very clear that not only do we need to match the right drug with the right patient subgroup but we also need biomarkers that will help guide our decision. One of the most exciting aspects of the DISRUPTOR-1 trial data is the identification of biomarkers that change in response to the BNC105 + Afinitor treatment. Most importantly, statistical significance was demonstrated for several of these biomarker changes associated with the disease progressing or not at 6 months in patients treated with the BNC105 + Afinitor combination,” Dr Hutson added.
Biomarkers identified associated with PFS at 6 months
In the DISRUPTOR-1 trial plasma biomarkers previously associated with BNC105 activity were analysed and this was a pre-specified exploratory endpoint. Logistic regression analysis demonstrated that biomarker changes were associated with disease progression at 6 months, in a statistically significant manner. The p-values associated with these changes span the range of 0.0136 to 0.0348.
“The association of significant biomarker changes with an important parameter of disease control such as progression-free-survival is to the best of our knowledge demonstrated for the first time with this study in renal cell carcinoma patients,” said Dr José Iglesias, Bionomics’ Chief Medical Officer.
“BNC105 has the potential to change the way renal cancer is treated and the DISRUPTOR-1 trial has given us an insight on those patients who respond best to treatment. This is valuable information to incorporate in future clinical trial design and from the regulatory and reimbursement perspectives,” Dr Iglesias added.
Determination of overall survival over a period of 5 years, overall response rate of the combination and PFS of BNC105 monotherapy following Afinitor treatment data are still pending.
Data collection and analysis on these parameters is continuing and will be reported as it becomes available in scientific presentations and publications.
SOURCE: Bionomics
- Results show BNC105 utility in patients with advanced disease
- Identified biomarkers which correlate with patient benefit (progression free survival at 6 months)
- Addition of BNC105 to Afinitor treatment delayed disease progression in patient subgroups identified on the basis of metastases, previous nephrectomy and Fuhrman tumour differentiation grade
- Primary endpoint showed a similar proportion of patients in both treatment arms free of progression at 6 months in the unselected patient population
ADELAIDE, South Australia, March 18, 2014 (GLOBE NEWSWIRE) — Bionomics Limited (ASX:BNO) (ADR:BMICY) today announced the results of the DISRUPTOR-1 trial of BNC105 in patients with metastatic renal cancer.
“The DISRUPTOR-1 trial has been the first of its kind in testing the combination of an mTOR inhibitor with a vascular disrupting agent in renal cancer, with the prospect of adding a new dimension to the renal cancer treatment armamentarium,” said Dr Deborah Rathjen, Bionomics’ CEO & Managing Director.
“Significant progress has been made in validating BNC105 as an anti-cancer agent. Through patient subgroup analysis and association of biomarkers to treatment benefit, the data from this trial shows us the best way forward to maximising the utility of BNC105 for renal cancer patients, as well as how to best employ the drug in other cancer types.”
“DISRUPTOR-1 has produced a ground-breaking discovery of potential biomarkers that may allow pre-treatment selection of patients most likely to benefit from BNC105.”
“We are exploring partnership opportunities for BNC105 and expect to attract a depth of interest given the compelling data generated from this trial and the recent ovarian cancer trial data,” Dr Rathjen added.
Outline of the DISRUPTOR-1 trial
Bionomics conducted this randomised Phase II clinical trial in patients with metastatic renal cell cancer with 139 patients enrolled at sites across the US, Singapore and Australia.
The trial design targeted patients who had previously failed up to two tyrosine kinase inhibitor therapies, randomising them to either of two treatment arms: one receiving the standard of care renal cancer drug Afinitor and the other receiving both Afinitor and BNC105. Patients who were progressing or who were intolerant to Afinitor monotherapy, were allowed to receive BNC105 single agent treatment. Patients were treated until disease progression or until adverse effects prohibited further therapy.
Data from a total of 136 patients (69 in the BNC105 + Afinitor arm and 67 in the Afinitor-only arm) treated in this study were able to be analysed. The combination of BNC105 and Afinitor was safe and tolerable. The adverse event profile of the combination arm did not significantly differ from that of the Afinitor-only arm, and mirrored the known and expected toxicities of Afinitor.
BNC105 combination treatment benefited patients with more advanced disease
In relation to the primary endpoint, the proportion of patients free of progression at 6 months in the unselected patient population was similar between the two arms (23 patients in the BNC105 + Afinitor arm, vs 20 patients in the Afinitor-only arm, roughly 1/3 of the patients in each arm, p=0.6625). The median Progression Free Survival (PFS) in the unselected patient population was also similar between the study arms (4.7 months in the BNC105 + Afinitor arm vs 4.1 months in the Afinitor-only arm).
An analysis of patient subgroups indicated that a 3.8 month increase in PFS favouring the BNC105 + Afinitor combination over Afinitor-only monotherapy was observed in patients with liver metastases (6.6 months vs. 2.8 months) . Metastatic lesions to the liver adversely affect prognosis, with an average 5-year survival rate of approximately 30%.
Patients with a previous nephrectomy (kidney removal) also showed a trend to improved PFS with the BNC105 + Afinitor combination than with Afinitor alone (7.1 months vs 4.1 months) with a 3 month improvement in PFS.
PFS in the BNC105 + Afinitor arm was increased by approximately 50% (from 4.1 to 6.4 months) in patients with Furhman Grade 2 histological differentiation grade. Furhman grade, based on nuclear and nucleolar morphology, is an independent prognostic factor for survival.
Taken together these results indicate that future clinical trials of BNC105 in renal cell carcinoma should be enriched for these patient subgroups.
“Defining responder patient subgroups is very important. Several drugs are now available for renal cancer patients. The latest experience suggests that we need to be more targeted in matching up the right drug with the right patient subpopulation. This need is becoming clearly evident for a number of agents currently in use in the renal cancer setting,” commented Dr Thomas E Hutson.
Dr Hutson is Director, GU Oncology, Charles A Sammons Cancer Center, Baylor University Medical Center, and Professor of Medicine, at the Texas A&M HSC College of Medicine. Dr Hutson was the global Principal Investigator for the DISRUPTOR-1 clinical trial.
“It is very clear that not only do we need to match the right drug with the right patient subgroup but we also need biomarkers that will help guide our decision. One of the most exciting aspects of the DISRUPTOR-1 trial data is the identification of biomarkers that change in response to the BNC105 + Afinitor treatment. Most importantly, statistical significance was demonstrated for several of these biomarker changes associated with the disease progressing or not at 6 months in patients treated with the BNC105 + Afinitor combination,” Dr Hutson added.
Biomarkers identified associated with PFS at 6 months
In the DISRUPTOR-1 trial plasma biomarkers previously associated with BNC105 activity were analysed and this was a pre-specified exploratory endpoint. Logistic regression analysis demonstrated that biomarker changes were associated with disease progression at 6 months, in a statistically significant manner. The p-values associated with these changes span the range of 0.0136 to 0.0348.
“The association of significant biomarker changes with an important parameter of disease control such as progression-free-survival is to the best of our knowledge demonstrated for the first time with this study in renal cell carcinoma patients,” said Dr José Iglesias, Bionomics’ Chief Medical Officer.
“BNC105 has the potential to change the way renal cancer is treated and the DISRUPTOR-1 trial has given us an insight on those patients who respond best to treatment. This is valuable information to incorporate in future clinical trial design and from the regulatory and reimbursement perspectives,” Dr Iglesias added.
Determination of overall survival over a period of 5 years, overall response rate of the combination and PFS of BNC105 monotherapy following Afinitor treatment data are still pending.
Data collection and analysis on these parameters is continuing and will be reported as it becomes available in scientific presentations and publications.
– See more at: http://www.globenewswire.com/news-release/2014/03/18/619339/10073183/en/BNC105-Phase-II-Renal-Cancer-Trial-Results.html#sthash.4GA36PCK.dpuf
- Results show BNC105 utility in patients with advanced disease
- Identified biomarkers which correlate with patient benefit (progression free survival at 6 months)
- Addition of BNC105 to Afinitor treatment delayed disease progression in patient subgroups identified on the basis of metastases, previous nephrectomy and Fuhrman tumour differentiation grade
- Primary endpoint showed a similar proportion of patients in both treatment arms free of progression at 6 months in the unselected patient population
ADELAIDE, South Australia, March 18, 2014 (GLOBE NEWSWIRE) — Bionomics Limited (ASX:BNO) (ADR:BMICY) today announced the results of the DISRUPTOR-1 trial of BNC105 in patients with metastatic renal cancer.
“The DISRUPTOR-1 trial has been the first of its kind in testing the combination of an mTOR inhibitor with a vascular disrupting agent in renal cancer, with the prospect of adding a new dimension to the renal cancer treatment armamentarium,” said Dr Deborah Rathjen, Bionomics’ CEO & Managing Director.
“Significant progress has been made in validating BNC105 as an anti-cancer agent. Through patient subgroup analysis and association of biomarkers to treatment benefit, the data from this trial shows us the best way forward to maximising the utility of BNC105 for renal cancer patients, as well as how to best employ the drug in other cancer types.”
“DISRUPTOR-1 has produced a ground-breaking discovery of potential biomarkers that may allow pre-treatment selection of patients most likely to benefit from BNC105.”
“We are exploring partnership opportunities for BNC105 and expect to attract a depth of interest given the compelling data generated from this trial and the recent ovarian cancer trial data,” Dr Rathjen added.
Outline of the DISRUPTOR-1 trial
Bionomics conducted this randomised Phase II clinical trial in patients with metastatic renal cell cancer with 139 patients enrolled at sites across the US, Singapore and Australia.
The trial design targeted patients who had previously failed up to two tyrosine kinase inhibitor therapies, randomising them to either of two treatment arms: one receiving the standard of care renal cancer drug Afinitor and the other receiving both Afinitor and BNC105. Patients who were progressing or who were intolerant to Afinitor monotherapy, were allowed to receive BNC105 single agent treatment. Patients were treated until disease progression or until adverse effects prohibited further therapy.
Data from a total of 136 patients (69 in the BNC105 + Afinitor arm and 67 in the Afinitor-only arm) treated in this study were able to be analysed. The combination of BNC105 and Afinitor was safe and tolerable. The adverse event profile of the combination arm did not significantly differ from that of the Afinitor-only arm, and mirrored the known and expected toxicities of Afinitor.
BNC105 combination treatment benefited patients with more advanced disease
In relation to the primary endpoint, the proportion of patients free of progression at 6 months in the unselected patient population was similar between the two arms (23 patients in the BNC105 + Afinitor arm, vs 20 patients in the Afinitor-only arm, roughly 1/3 of the patients in each arm, p=0.6625). The median Progression Free Survival (PFS) in the unselected patient population was also similar between the study arms (4.7 months in the BNC105 + Afinitor arm vs 4.1 months in the Afinitor-only arm).
An analysis of patient subgroups indicated that a 3.8 month increase in PFS favouring the BNC105 + Afinitor combination over Afinitor-only monotherapy was observed in patients with liver metastases (6.6 months vs. 2.8 months) . Metastatic lesions to the liver adversely affect prognosis, with an average 5-year survival rate of approximately 30%.
Patients with a previous nephrectomy (kidney removal) also showed a trend to improved PFS with the BNC105 + Afinitor combination than with Afinitor alone (7.1 months vs 4.1 months) with a 3 month improvement in PFS.
PFS in the BNC105 + Afinitor arm was increased by approximately 50% (from 4.1 to 6.4 months) in patients with Furhman Grade 2 histological differentiation grade. Furhman grade, based on nuclear and nucleolar morphology, is an independent prognostic factor for survival.
Taken together these results indicate that future clinical trials of BNC105 in renal cell carcinoma should be enriched for these patient subgroups.
“Defining responder patient subgroups is very important. Several drugs are now available for renal cancer patients. The latest experience suggests that we need to be more targeted in matching up the right drug with the right patient subpopulation. This need is becoming clearly evident for a number of agents currently in use in the renal cancer setting,” commented Dr Thomas E Hutson.
Dr Hutson is Director, GU Oncology, Charles A Sammons Cancer Center, Baylor University Medical Center, and Professor of Medicine, at the Texas A&M HSC College of Medicine. Dr Hutson was the global Principal Investigator for the DISRUPTOR-1 clinical trial.
“It is very clear that not only do we need to match the right drug with the right patient subgroup but we also need biomarkers that will help guide our decision. One of the most exciting aspects of the DISRUPTOR-1 trial data is the identification of biomarkers that change in response to the BNC105 + Afinitor treatment. Most importantly, statistical significance was demonstrated for several of these biomarker changes associated with the disease progressing or not at 6 months in patients treated with the BNC105 + Afinitor combination,” Dr Hutson added.
Biomarkers identified associated with PFS at 6 months
In the DISRUPTOR-1 trial plasma biomarkers previously associated with BNC105 activity were analysed and this was a pre-specified exploratory endpoint. Logistic regression analysis demonstrated that biomarker changes were associated with disease progression at 6 months, in a statistically significant manner. The p-values associated with these changes span the range of 0.0136 to 0.0348.
“The association of significant biomarker changes with an important parameter of disease control such as progression-free-survival is to the best of our knowledge demonstrated for the first time with this study in renal cell carcinoma patients,” said Dr José Iglesias, Bionomics’ Chief Medical Officer.
“BNC105 has the potential to change the way renal cancer is treated and the DISRUPTOR-1 trial has given us an insight on those patients who respond best to treatment. This is valuable information to incorporate in future clinical trial design and from the regulatory and reimbursement perspectives,” Dr Iglesias added.
Determination of overall survival over a period of 5 years, overall response rate of the combination and PFS of BNC105 monotherapy following Afinitor treatment data are still pending.
Data collection and analysis on these parameters is continuing and will be reported as it becomes available in scientific presentations and publications.
– See more at: http://www.globenewswire.com/news-release/2014/03/18/619339/10073183/en/BNC105-Phase-II-Renal-Cancer-Trial-Results.html#sthash.4GA36PCK.dpuf
- Results show BNC105 utility in patients with advanced disease
- Identified biomarkers which correlate with patient benefit (progression free survival at 6 months)
- Addition of BNC105 to Afinitor treatment delayed disease progression in patient subgroups identified on the basis of metastases, previous nephrectomy and Fuhrman tumour differentiation grade
- Primary endpoint showed a similar proportion of patients in both treatment arms free of progression at 6 months in the unselected patient population
ADELAIDE, South Australia, March 18, 2014 (GLOBE NEWSWIRE) — Bionomics Limited (ASX:BNO) (ADR:BMICY) today announced the results of the DISRUPTOR-1 trial of BNC105 in patients with metastatic renal cancer.
“The DISRUPTOR-1 trial has been the first of its kind in testing the combination of an mTOR inhibitor with a vascular disrupting agent in renal cancer, with the prospect of adding a new dimension to the renal cancer treatment armamentarium,” said Dr Deborah Rathjen, Bionomics’ CEO & Managing Director.
“Significant progress has been made in validating BNC105 as an anti-cancer agent. Through patient subgroup analysis and association of biomarkers to treatment benefit, the data from this trial shows us the best way forward to maximising the utility of BNC105 for renal cancer patients, as well as how to best employ the drug in other cancer types.”
“DISRUPTOR-1 has produced a ground-breaking discovery of potential biomarkers that may allow pre-treatment selection of patients most likely to benefit from BNC105.”
“We are exploring partnership opportunities for BNC105 and expect to attract a depth of interest given the compelling data generated from this trial and the recent ovarian cancer trial data,” Dr Rathjen added.
Outline of the DISRUPTOR-1 trial
Bionomics conducted this randomised Phase II clinical trial in patients with metastatic renal cell cancer with 139 patients enrolled at sites across the US, Singapore and Australia.
The trial design targeted patients who had previously failed up to two tyrosine kinase inhibitor therapies, randomising them to either of two treatment arms: one receiving the standard of care renal cancer drug Afinitor and the other receiving both Afinitor and BNC105. Patients who were progressing or who were intolerant to Afinitor monotherapy, were allowed to receive BNC105 single agent treatment. Patients were treated until disease progression or until adverse effects prohibited further therapy.
Data from a total of 136 patients (69 in the BNC105 + Afinitor arm and 67 in the Afinitor-only arm) treated in this study were able to be analysed. The combination of BNC105 and Afinitor was safe and tolerable. The adverse event profile of the combination arm did not significantly differ from that of the Afinitor-only arm, and mirrored the known and expected toxicities of Afinitor.
BNC105 combination treatment benefited patients with more advanced disease
In relation to the primary endpoint, the proportion of patients free of progression at 6 months in the unselected patient population was similar between the two arms (23 patients in the BNC105 + Afinitor arm, vs 20 patients in the Afinitor-only arm, roughly 1/3 of the patients in each arm, p=0.6625). The median Progression Free Survival (PFS) in the unselected patient population was also similar between the study arms (4.7 months in the BNC105 + Afinitor arm vs 4.1 months in the Afinitor-only arm).
An analysis of patient subgroups indicated that a 3.8 month increase in PFS favouring the BNC105 + Afinitor combination over Afinitor-only monotherapy was observed in patients with liver metastases (6.6 months vs. 2.8 months) . Metastatic lesions to the liver adversely affect prognosis, with an average 5-year survival rate of approximately 30%.
Patients with a previous nephrectomy (kidney removal) also showed a trend to improved PFS with the BNC105 + Afinitor combination than with Afinitor alone (7.1 months vs 4.1 months) with a 3 month improvement in PFS.
PFS in the BNC105 + Afinitor arm was increased by approximately 50% (from 4.1 to 6.4 months) in patients with Furhman Grade 2 histological differentiation grade. Furhman grade, based on nuclear and nucleolar morphology, is an independent prognostic factor for survival.
Taken together these results indicate that future clinical trials of BNC105 in renal cell carcinoma should be enriched for these patient subgroups.
“Defining responder patient subgroups is very important. Several drugs are now available for renal cancer patients. The latest experience suggests that we need to be more targeted in matching up the right drug with the right patient subpopulation. This need is becoming clearly evident for a number of agents currently in use in the renal cancer setting,” commented Dr Thomas E Hutson.
Dr Hutson is Director, GU Oncology, Charles A Sammons Cancer Center, Baylor University Medical Center, and Professor of Medicine, at the Texas A&M HSC College of Medicine. Dr Hutson was the global Principal Investigator for the DISRUPTOR-1 clinical trial.
“It is very clear that not only do we need to match the right drug with the right patient subgroup but we also need biomarkers that will help guide our decision. One of the most exciting aspects of the DISRUPTOR-1 trial data is the identification of biomarkers that change in response to the BNC105 + Afinitor treatment. Most importantly, statistical significance was demonstrated for several of these biomarker changes associated with the disease progressing or not at 6 months in patients treated with the BNC105 + Afinitor combination,” Dr Hutson added.
Biomarkers identified associated with PFS at 6 months
In the DISRUPTOR-1 trial plasma biomarkers previously associated with BNC105 activity were analysed and this was a pre-specified exploratory endpoint. Logistic regression analysis demonstrated that biomarker changes were associated with disease progression at 6 months, in a statistically significant manner. The p-values associated with these changes span the range of 0.0136 to 0.0348.
“The association of significant biomarker changes with an important parameter of disease control such as progression-free-survival is to the best of our knowledge demonstrated for the first time with this study in renal cell carcinoma patients,” said Dr José Iglesias, Bionomics’ Chief Medical Officer.
“BNC105 has the potential to change the way renal cancer is treated and the DISRUPTOR-1 trial has given us an insight on those patients who respond best to treatment. This is valuable information to incorporate in future clinical trial design and from the regulatory and reimbursement perspectives,” Dr Iglesias added.
Determination of overall survival over a period of 5 years, overall response rate of the combination and PFS of BNC105 monotherapy following Afinitor treatment data are still pending.
Data collection and analysis on these parameters is continuing and will be reported as it becomes available in scientific presentations and publications.
– See more at: http://www.globenewswire.com/news-release/2014/03/18/619339/10073183/en/BNC105-Phase-II-Renal-Cancer-Trial-Results.html#sthash.4GA36PCK.dpuf
Post Views: 114
-
Results show BNC105 utility in patients with advanced disease
-
Identified biomarkers which correlate with patient benefit (progression free survival at 6 months)
-
Addition of BNC105 to Afinitor treatment delayed disease progression in patient subgroups identified on the basis of metastases, previous nephrectomy and Fuhrman tumour differentiation grade
-
Primary endpoint showed a similar proportion of patients in both treatment arms free of progression at 6 months in the unselected patient population
ADELAIDE, Australia I March 18, 2014 I Bionomics Limited (ASX:BNO) (ADR:BMICY) today announced the results of the DISRUPTOR-1 trial of BNC105 in patients with metastatic renal cancer.
“The DISRUPTOR-1 trial has been the first of its kind in testing the combination of an mTOR inhibitor with a vascular disrupting agent in renal cancer, with the prospect of adding a new dimension to the renal cancer treatment armamentarium,” said Dr Deborah Rathjen, Bionomics’ CEO & Managing Director.
“Significant progress has been made in validating BNC105 as an anti-cancer agent. Through patient subgroup analysis and association of biomarkers to treatment benefit, the data from this trial shows us the best way forward to maximising the utility of BNC105 for renal cancer patients, as well as how to best employ the drug in other cancer types.”
“DISRUPTOR-1 has produced a ground-breaking discovery of potential biomarkers that may allow pre-treatment selection of patients most likely to benefit from BNC105.”
“We are exploring partnership opportunities for BNC105 and expect to attract a depth of interest given the compelling data generated from this trial and the recent ovarian cancer trial data,” Dr Rathjen added.
Outline of the DISRUPTOR-1 trial
Bionomics conducted this randomised Phase II clinical trial in patients with metastatic renal cell cancer with 139 patients enrolled at sites across the US, Singapore and Australia.
The trial design targeted patients who had previously failed up to two tyrosine kinase inhibitor therapies, randomising them to either of two treatment arms: one receiving the standard of care renal cancer drug Afinitor and the other receiving both Afinitor and BNC105. Patients who were progressing or who were intolerant to Afinitor monotherapy, were allowed to receive BNC105 single agent treatment. Patients were treated until disease progression or until adverse effects prohibited further therapy.
Data from a total of 136 patients (69 in the BNC105 + Afinitor arm and 67 in the Afinitor-only arm) treated in this study were able to be analysed. The combination of BNC105 and Afinitor was safe and tolerable. The adverse event profile of the combination arm did not significantly differ from that of the Afinitor-only arm, and mirrored the known and expected toxicities of Afinitor.
BNC105 combination treatment benefited patients with more advanced disease
In relation to the primary endpoint, the proportion of patients free of progression at 6 months in the unselected patient population was similar between the two arms (23 patients in the BNC105 + Afinitor arm, vs 20 patients in the Afinitor-only arm, roughly 1/3 of the patients in each arm, p=0.6625). The median Progression Free Survival (PFS) in the unselected patient population was also similar between the study arms (4.7 months in the BNC105 + Afinitor arm vs 4.1 months in the Afinitor-only arm).
An analysis of patient subgroups indicated that a 3.8 month increase in PFS favouring the BNC105 + Afinitor combination over Afinitor-only monotherapy was observed in patients with liver metastases (6.6 months vs. 2.8 months) . Metastatic lesions to the liver adversely affect prognosis, with an average 5-year survival rate of approximately 30%.
Patients with a previous nephrectomy (kidney removal) also showed a trend to improved PFS with the BNC105 + Afinitor combination than with Afinitor alone (7.1 months vs 4.1 months) with a 3 month improvement in PFS.
PFS in the BNC105 + Afinitor arm was increased by approximately 50% (from 4.1 to 6.4 months) in patients with Furhman Grade 2 histological differentiation grade. Furhman grade, based on nuclear and nucleolar morphology, is an independent prognostic factor for survival.
Taken together these results indicate that future clinical trials of BNC105 in renal cell carcinoma should be enriched for these patient subgroups.
“Defining responder patient subgroups is very important. Several drugs are now available for renal cancer patients. The latest experience suggests that we need to be more targeted in matching up the right drug with the right patient subpopulation. This need is becoming clearly evident for a number of agents currently in use in the renal cancer setting,” commented Dr Thomas E Hutson.
Dr Hutson is Director, GU Oncology, Charles A Sammons Cancer Center, Baylor University Medical Center, and Professor of Medicine, at the Texas A&M HSC College of Medicine. Dr Hutson was the global Principal Investigator for the DISRUPTOR-1 clinical trial.
“It is very clear that not only do we need to match the right drug with the right patient subgroup but we also need biomarkers that will help guide our decision. One of the most exciting aspects of the DISRUPTOR-1 trial data is the identification of biomarkers that change in response to the BNC105 + Afinitor treatment. Most importantly, statistical significance was demonstrated for several of these biomarker changes associated with the disease progressing or not at 6 months in patients treated with the BNC105 + Afinitor combination,” Dr Hutson added.
Biomarkers identified associated with PFS at 6 months
In the DISRUPTOR-1 trial plasma biomarkers previously associated with BNC105 activity were analysed and this was a pre-specified exploratory endpoint. Logistic regression analysis demonstrated that biomarker changes were associated with disease progression at 6 months, in a statistically significant manner. The p-values associated with these changes span the range of 0.0136 to 0.0348.
“The association of significant biomarker changes with an important parameter of disease control such as progression-free-survival is to the best of our knowledge demonstrated for the first time with this study in renal cell carcinoma patients,” said Dr José Iglesias, Bionomics’ Chief Medical Officer.
“BNC105 has the potential to change the way renal cancer is treated and the DISRUPTOR-1 trial has given us an insight on those patients who respond best to treatment. This is valuable information to incorporate in future clinical trial design and from the regulatory and reimbursement perspectives,” Dr Iglesias added.
Determination of overall survival over a period of 5 years, overall response rate of the combination and PFS of BNC105 monotherapy following Afinitor treatment data are still pending.
Data collection and analysis on these parameters is continuing and will be reported as it becomes available in scientific presentations and publications.
SOURCE: Bionomics
- Results show BNC105 utility in patients with advanced disease
- Identified biomarkers which correlate with patient benefit (progression free survival at 6 months)
- Addition of BNC105 to Afinitor treatment delayed disease progression in patient subgroups identified on the basis of metastases, previous nephrectomy and Fuhrman tumour differentiation grade
- Primary endpoint showed a similar proportion of patients in both treatment arms free of progression at 6 months in the unselected patient population
ADELAIDE, South Australia, March 18, 2014 (GLOBE NEWSWIRE) — Bionomics Limited (ASX:BNO) (ADR:BMICY) today announced the results of the DISRUPTOR-1 trial of BNC105 in patients with metastatic renal cancer.
“The DISRUPTOR-1 trial has been the first of its kind in testing the combination of an mTOR inhibitor with a vascular disrupting agent in renal cancer, with the prospect of adding a new dimension to the renal cancer treatment armamentarium,” said Dr Deborah Rathjen, Bionomics’ CEO & Managing Director.
“Significant progress has been made in validating BNC105 as an anti-cancer agent. Through patient subgroup analysis and association of biomarkers to treatment benefit, the data from this trial shows us the best way forward to maximising the utility of BNC105 for renal cancer patients, as well as how to best employ the drug in other cancer types.”
“DISRUPTOR-1 has produced a ground-breaking discovery of potential biomarkers that may allow pre-treatment selection of patients most likely to benefit from BNC105.”
“We are exploring partnership opportunities for BNC105 and expect to attract a depth of interest given the compelling data generated from this trial and the recent ovarian cancer trial data,” Dr Rathjen added.
Outline of the DISRUPTOR-1 trial
Bionomics conducted this randomised Phase II clinical trial in patients with metastatic renal cell cancer with 139 patients enrolled at sites across the US, Singapore and Australia.
The trial design targeted patients who had previously failed up to two tyrosine kinase inhibitor therapies, randomising them to either of two treatment arms: one receiving the standard of care renal cancer drug Afinitor and the other receiving both Afinitor and BNC105. Patients who were progressing or who were intolerant to Afinitor monotherapy, were allowed to receive BNC105 single agent treatment. Patients were treated until disease progression or until adverse effects prohibited further therapy.
Data from a total of 136 patients (69 in the BNC105 + Afinitor arm and 67 in the Afinitor-only arm) treated in this study were able to be analysed. The combination of BNC105 and Afinitor was safe and tolerable. The adverse event profile of the combination arm did not significantly differ from that of the Afinitor-only arm, and mirrored the known and expected toxicities of Afinitor.
BNC105 combination treatment benefited patients with more advanced disease
In relation to the primary endpoint, the proportion of patients free of progression at 6 months in the unselected patient population was similar between the two arms (23 patients in the BNC105 + Afinitor arm, vs 20 patients in the Afinitor-only arm, roughly 1/3 of the patients in each arm, p=0.6625). The median Progression Free Survival (PFS) in the unselected patient population was also similar between the study arms (4.7 months in the BNC105 + Afinitor arm vs 4.1 months in the Afinitor-only arm).
An analysis of patient subgroups indicated that a 3.8 month increase in PFS favouring the BNC105 + Afinitor combination over Afinitor-only monotherapy was observed in patients with liver metastases (6.6 months vs. 2.8 months) . Metastatic lesions to the liver adversely affect prognosis, with an average 5-year survival rate of approximately 30%.
Patients with a previous nephrectomy (kidney removal) also showed a trend to improved PFS with the BNC105 + Afinitor combination than with Afinitor alone (7.1 months vs 4.1 months) with a 3 month improvement in PFS.
PFS in the BNC105 + Afinitor arm was increased by approximately 50% (from 4.1 to 6.4 months) in patients with Furhman Grade 2 histological differentiation grade. Furhman grade, based on nuclear and nucleolar morphology, is an independent prognostic factor for survival.
Taken together these results indicate that future clinical trials of BNC105 in renal cell carcinoma should be enriched for these patient subgroups.
“Defining responder patient subgroups is very important. Several drugs are now available for renal cancer patients. The latest experience suggests that we need to be more targeted in matching up the right drug with the right patient subpopulation. This need is becoming clearly evident for a number of agents currently in use in the renal cancer setting,” commented Dr Thomas E Hutson.
Dr Hutson is Director, GU Oncology, Charles A Sammons Cancer Center, Baylor University Medical Center, and Professor of Medicine, at the Texas A&M HSC College of Medicine. Dr Hutson was the global Principal Investigator for the DISRUPTOR-1 clinical trial.
“It is very clear that not only do we need to match the right drug with the right patient subgroup but we also need biomarkers that will help guide our decision. One of the most exciting aspects of the DISRUPTOR-1 trial data is the identification of biomarkers that change in response to the BNC105 + Afinitor treatment. Most importantly, statistical significance was demonstrated for several of these biomarker changes associated with the disease progressing or not at 6 months in patients treated with the BNC105 + Afinitor combination,” Dr Hutson added.
Biomarkers identified associated with PFS at 6 months
In the DISRUPTOR-1 trial plasma biomarkers previously associated with BNC105 activity were analysed and this was a pre-specified exploratory endpoint. Logistic regression analysis demonstrated that biomarker changes were associated with disease progression at 6 months, in a statistically significant manner. The p-values associated with these changes span the range of 0.0136 to 0.0348.
“The association of significant biomarker changes with an important parameter of disease control such as progression-free-survival is to the best of our knowledge demonstrated for the first time with this study in renal cell carcinoma patients,” said Dr José Iglesias, Bionomics’ Chief Medical Officer.
“BNC105 has the potential to change the way renal cancer is treated and the DISRUPTOR-1 trial has given us an insight on those patients who respond best to treatment. This is valuable information to incorporate in future clinical trial design and from the regulatory and reimbursement perspectives,” Dr Iglesias added.
Determination of overall survival over a period of 5 years, overall response rate of the combination and PFS of BNC105 monotherapy following Afinitor treatment data are still pending.
Data collection and analysis on these parameters is continuing and will be reported as it becomes available in scientific presentations and publications.
– See more at: http://www.globenewswire.com/news-release/2014/03/18/619339/10073183/en/BNC105-Phase-II-Renal-Cancer-Trial-Results.html#sthash.4GA36PCK.dpuf
- Results show BNC105 utility in patients with advanced disease
- Identified biomarkers which correlate with patient benefit (progression free survival at 6 months)
- Addition of BNC105 to Afinitor treatment delayed disease progression in patient subgroups identified on the basis of metastases, previous nephrectomy and Fuhrman tumour differentiation grade
- Primary endpoint showed a similar proportion of patients in both treatment arms free of progression at 6 months in the unselected patient population
ADELAIDE, South Australia, March 18, 2014 (GLOBE NEWSWIRE) — Bionomics Limited (ASX:BNO) (ADR:BMICY) today announced the results of the DISRUPTOR-1 trial of BNC105 in patients with metastatic renal cancer.
“The DISRUPTOR-1 trial has been the first of its kind in testing the combination of an mTOR inhibitor with a vascular disrupting agent in renal cancer, with the prospect of adding a new dimension to the renal cancer treatment armamentarium,” said Dr Deborah Rathjen, Bionomics’ CEO & Managing Director.
“Significant progress has been made in validating BNC105 as an anti-cancer agent. Through patient subgroup analysis and association of biomarkers to treatment benefit, the data from this trial shows us the best way forward to maximising the utility of BNC105 for renal cancer patients, as well as how to best employ the drug in other cancer types.”
“DISRUPTOR-1 has produced a ground-breaking discovery of potential biomarkers that may allow pre-treatment selection of patients most likely to benefit from BNC105.”
“We are exploring partnership opportunities for BNC105 and expect to attract a depth of interest given the compelling data generated from this trial and the recent ovarian cancer trial data,” Dr Rathjen added.
Outline of the DISRUPTOR-1 trial
Bionomics conducted this randomised Phase II clinical trial in patients with metastatic renal cell cancer with 139 patients enrolled at sites across the US, Singapore and Australia.
The trial design targeted patients who had previously failed up to two tyrosine kinase inhibitor therapies, randomising them to either of two treatment arms: one receiving the standard of care renal cancer drug Afinitor and the other receiving both Afinitor and BNC105. Patients who were progressing or who were intolerant to Afinitor monotherapy, were allowed to receive BNC105 single agent treatment. Patients were treated until disease progression or until adverse effects prohibited further therapy.
Data from a total of 136 patients (69 in the BNC105 + Afinitor arm and 67 in the Afinitor-only arm) treated in this study were able to be analysed. The combination of BNC105 and Afinitor was safe and tolerable. The adverse event profile of the combination arm did not significantly differ from that of the Afinitor-only arm, and mirrored the known and expected toxicities of Afinitor.
BNC105 combination treatment benefited patients with more advanced disease
In relation to the primary endpoint, the proportion of patients free of progression at 6 months in the unselected patient population was similar between the two arms (23 patients in the BNC105 + Afinitor arm, vs 20 patients in the Afinitor-only arm, roughly 1/3 of the patients in each arm, p=0.6625). The median Progression Free Survival (PFS) in the unselected patient population was also similar between the study arms (4.7 months in the BNC105 + Afinitor arm vs 4.1 months in the Afinitor-only arm).
An analysis of patient subgroups indicated that a 3.8 month increase in PFS favouring the BNC105 + Afinitor combination over Afinitor-only monotherapy was observed in patients with liver metastases (6.6 months vs. 2.8 months) . Metastatic lesions to the liver adversely affect prognosis, with an average 5-year survival rate of approximately 30%.
Patients with a previous nephrectomy (kidney removal) also showed a trend to improved PFS with the BNC105 + Afinitor combination than with Afinitor alone (7.1 months vs 4.1 months) with a 3 month improvement in PFS.
PFS in the BNC105 + Afinitor arm was increased by approximately 50% (from 4.1 to 6.4 months) in patients with Furhman Grade 2 histological differentiation grade. Furhman grade, based on nuclear and nucleolar morphology, is an independent prognostic factor for survival.
Taken together these results indicate that future clinical trials of BNC105 in renal cell carcinoma should be enriched for these patient subgroups.
“Defining responder patient subgroups is very important. Several drugs are now available for renal cancer patients. The latest experience suggests that we need to be more targeted in matching up the right drug with the right patient subpopulation. This need is becoming clearly evident for a number of agents currently in use in the renal cancer setting,” commented Dr Thomas E Hutson.
Dr Hutson is Director, GU Oncology, Charles A Sammons Cancer Center, Baylor University Medical Center, and Professor of Medicine, at the Texas A&M HSC College of Medicine. Dr Hutson was the global Principal Investigator for the DISRUPTOR-1 clinical trial.
“It is very clear that not only do we need to match the right drug with the right patient subgroup but we also need biomarkers that will help guide our decision. One of the most exciting aspects of the DISRUPTOR-1 trial data is the identification of biomarkers that change in response to the BNC105 + Afinitor treatment. Most importantly, statistical significance was demonstrated for several of these biomarker changes associated with the disease progressing or not at 6 months in patients treated with the BNC105 + Afinitor combination,” Dr Hutson added.
Biomarkers identified associated with PFS at 6 months
In the DISRUPTOR-1 trial plasma biomarkers previously associated with BNC105 activity were analysed and this was a pre-specified exploratory endpoint. Logistic regression analysis demonstrated that biomarker changes were associated with disease progression at 6 months, in a statistically significant manner. The p-values associated with these changes span the range of 0.0136 to 0.0348.
“The association of significant biomarker changes with an important parameter of disease control such as progression-free-survival is to the best of our knowledge demonstrated for the first time with this study in renal cell carcinoma patients,” said Dr José Iglesias, Bionomics’ Chief Medical Officer.
“BNC105 has the potential to change the way renal cancer is treated and the DISRUPTOR-1 trial has given us an insight on those patients who respond best to treatment. This is valuable information to incorporate in future clinical trial design and from the regulatory and reimbursement perspectives,” Dr Iglesias added.
Determination of overall survival over a period of 5 years, overall response rate of the combination and PFS of BNC105 monotherapy following Afinitor treatment data are still pending.
Data collection and analysis on these parameters is continuing and will be reported as it becomes available in scientific presentations and publications.
– See more at: http://www.globenewswire.com/news-release/2014/03/18/619339/10073183/en/BNC105-Phase-II-Renal-Cancer-Trial-Results.html#sthash.4GA36PCK.dpuf
- Results show BNC105 utility in patients with advanced disease
- Identified biomarkers which correlate with patient benefit (progression free survival at 6 months)
- Addition of BNC105 to Afinitor treatment delayed disease progression in patient subgroups identified on the basis of metastases, previous nephrectomy and Fuhrman tumour differentiation grade
- Primary endpoint showed a similar proportion of patients in both treatment arms free of progression at 6 months in the unselected patient population
ADELAIDE, South Australia, March 18, 2014 (GLOBE NEWSWIRE) — Bionomics Limited (ASX:BNO) (ADR:BMICY) today announced the results of the DISRUPTOR-1 trial of BNC105 in patients with metastatic renal cancer.
“The DISRUPTOR-1 trial has been the first of its kind in testing the combination of an mTOR inhibitor with a vascular disrupting agent in renal cancer, with the prospect of adding a new dimension to the renal cancer treatment armamentarium,” said Dr Deborah Rathjen, Bionomics’ CEO & Managing Director.
“Significant progress has been made in validating BNC105 as an anti-cancer agent. Through patient subgroup analysis and association of biomarkers to treatment benefit, the data from this trial shows us the best way forward to maximising the utility of BNC105 for renal cancer patients, as well as how to best employ the drug in other cancer types.”
“DISRUPTOR-1 has produced a ground-breaking discovery of potential biomarkers that may allow pre-treatment selection of patients most likely to benefit from BNC105.”
“We are exploring partnership opportunities for BNC105 and expect to attract a depth of interest given the compelling data generated from this trial and the recent ovarian cancer trial data,” Dr Rathjen added.
Outline of the DISRUPTOR-1 trial
Bionomics conducted this randomised Phase II clinical trial in patients with metastatic renal cell cancer with 139 patients enrolled at sites across the US, Singapore and Australia.
The trial design targeted patients who had previously failed up to two tyrosine kinase inhibitor therapies, randomising them to either of two treatment arms: one receiving the standard of care renal cancer drug Afinitor and the other receiving both Afinitor and BNC105. Patients who were progressing or who were intolerant to Afinitor monotherapy, were allowed to receive BNC105 single agent treatment. Patients were treated until disease progression or until adverse effects prohibited further therapy.
Data from a total of 136 patients (69 in the BNC105 + Afinitor arm and 67 in the Afinitor-only arm) treated in this study were able to be analysed. The combination of BNC105 and Afinitor was safe and tolerable. The adverse event profile of the combination arm did not significantly differ from that of the Afinitor-only arm, and mirrored the known and expected toxicities of Afinitor.
BNC105 combination treatment benefited patients with more advanced disease
In relation to the primary endpoint, the proportion of patients free of progression at 6 months in the unselected patient population was similar between the two arms (23 patients in the BNC105 + Afinitor arm, vs 20 patients in the Afinitor-only arm, roughly 1/3 of the patients in each arm, p=0.6625). The median Progression Free Survival (PFS) in the unselected patient population was also similar between the study arms (4.7 months in the BNC105 + Afinitor arm vs 4.1 months in the Afinitor-only arm).
An analysis of patient subgroups indicated that a 3.8 month increase in PFS favouring the BNC105 + Afinitor combination over Afinitor-only monotherapy was observed in patients with liver metastases (6.6 months vs. 2.8 months) . Metastatic lesions to the liver adversely affect prognosis, with an average 5-year survival rate of approximately 30%.
Patients with a previous nephrectomy (kidney removal) also showed a trend to improved PFS with the BNC105 + Afinitor combination than with Afinitor alone (7.1 months vs 4.1 months) with a 3 month improvement in PFS.
PFS in the BNC105 + Afinitor arm was increased by approximately 50% (from 4.1 to 6.4 months) in patients with Furhman Grade 2 histological differentiation grade. Furhman grade, based on nuclear and nucleolar morphology, is an independent prognostic factor for survival.
Taken together these results indicate that future clinical trials of BNC105 in renal cell carcinoma should be enriched for these patient subgroups.
“Defining responder patient subgroups is very important. Several drugs are now available for renal cancer patients. The latest experience suggests that we need to be more targeted in matching up the right drug with the right patient subpopulation. This need is becoming clearly evident for a number of agents currently in use in the renal cancer setting,” commented Dr Thomas E Hutson.
Dr Hutson is Director, GU Oncology, Charles A Sammons Cancer Center, Baylor University Medical Center, and Professor of Medicine, at the Texas A&M HSC College of Medicine. Dr Hutson was the global Principal Investigator for the DISRUPTOR-1 clinical trial.
“It is very clear that not only do we need to match the right drug with the right patient subgroup but we also need biomarkers that will help guide our decision. One of the most exciting aspects of the DISRUPTOR-1 trial data is the identification of biomarkers that change in response to the BNC105 + Afinitor treatment. Most importantly, statistical significance was demonstrated for several of these biomarker changes associated with the disease progressing or not at 6 months in patients treated with the BNC105 + Afinitor combination,” Dr Hutson added.
Biomarkers identified associated with PFS at 6 months
In the DISRUPTOR-1 trial plasma biomarkers previously associated with BNC105 activity were analysed and this was a pre-specified exploratory endpoint. Logistic regression analysis demonstrated that biomarker changes were associated with disease progression at 6 months, in a statistically significant manner. The p-values associated with these changes span the range of 0.0136 to 0.0348.
“The association of significant biomarker changes with an important parameter of disease control such as progression-free-survival is to the best of our knowledge demonstrated for the first time with this study in renal cell carcinoma patients,” said Dr José Iglesias, Bionomics’ Chief Medical Officer.
“BNC105 has the potential to change the way renal cancer is treated and the DISRUPTOR-1 trial has given us an insight on those patients who respond best to treatment. This is valuable information to incorporate in future clinical trial design and from the regulatory and reimbursement perspectives,” Dr Iglesias added.
Determination of overall survival over a period of 5 years, overall response rate of the combination and PFS of BNC105 monotherapy following Afinitor treatment data are still pending.
Data collection and analysis on these parameters is continuing and will be reported as it becomes available in scientific presentations and publications.
– See more at: http://www.globenewswire.com/news-release/2014/03/18/619339/10073183/en/BNC105-Phase-II-Renal-Cancer-Trial-Results.html#sthash.4GA36PCK.dpuf
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