Abstracts for European Society of Medical Oncology (ESMO) available online on Wednesday, 28th September 2016 12.00 (CET)
Cisplatin and APO010 abstracts accepted for poster presentation at ESMO Annual Congress 2016 in Copenhagen, Denmark will be available online on the ESMO website http://www.esmo.org/
on Wednesday, September 28th 2016 at 12.00 (CET). Below are the two abstracts in English.
ESMO is the leading European professional organization for medical oncology. Comprising more than 13,000 oncology professionals from over 130 countries. ESMO is the society of reference for oncology education and information.
“Combining APO010 with DRP analysis will add a precision medicine element to immuno-oncology treatment of Multiple Myeloma. The DRP method will enable us to identify patients with high likelihood of response and thereby facilitate focused future trial design and patient recruitment to achieve clinical success. I look very much forward to the presentation of the prediction method at the largest oncology congress in Europe,” Said Adjunct Professor Peter Buhl Jensen, M.D., CEO of Oncology Venture.
“Cisplatin is one of the most used chemotherapies in the world and there is a need for biomarkers to predict efficacy of the drug. Oncology Venture is running a Proof of Concept clinical trial with LiPlaCis, a liposomal formulation of cisplatin, in breast cancer and I expect the data to be presented for the DRP in lung cancer at this years’ ESMO is supportive for the Breast Cancer study as well.” Buhl Jensen further commented.
ESMO venue: Bella Center, Center Boulevard 5, 2300 Copenhagen, Denmark.
Poster # 1187P:
Multigene expression profile for predicting efficacy of cisplatin and vinorelbine in non-small cell lung cancer
will be presented in Hall E, October 8th 2016 at 13-14 CET
Poster # 134P:
APO010 sensitivity in relapsed Multiple Myeloma patients
will be presented in Hall E, October 10th 2016 at 13-14 CET.
For further information, please contact
Ulla Hald Buhl, COO and
Chief IR & Communications
Mobile: +45 2170 1049
uhb@oncologyventure.com
or
Peter Buhl Jensen, CEO
Mobile: +45 21 60 89 22
pbj@oncologyventure.com
This information is information that Oncology Venture Sweden AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, on September 28th 2016.
Multigene expression profile for predicting efficacy of cisplatin and vinorelbine in non-small cell lung cancer
Ida Kappel Buhl1,2, Ib Jarle Christensen3, Eric Santoni-Rugiu4, Jesper Ravn5, Anker Hansen2, Thomas Jensen2, Jon Askaa2, Peter Buhl Jensen2, Steen Knudsen6, Jens Benn Sørensen7
1Section for Molecular Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 2Medical Prognosis Institute, Hoersholm, Denmark; 3Department of Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark, 4Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 5Department of Thoracic Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 6Medical Prognosis Institute Inc, Scottsdale, Arizona 85258, USA; 7Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Background
There is a need for biomarkers to predict efficacy of adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC). Presented is a combined cisplatin and vinorelbine marker from a previously validated model system [1] tested in two cohorts.Methods
The profiles consist of correlated in vitro cytotoxicity of cisplatin and vinorelbine and mRNA expressions. Then each profile is correlated to mRNA expression of 3500 tumors.
The cohorts are 1) a publically available dataset with 133 completely resected stage Ib-II NSCLC patients, 71 of whom received adjuvant cisplatin and vinorelbine (ACT) and 62 patients who had no adjuvant treatment (OBS) [2] and 2) 95 stage Ib-IIIb completely resected NSCLC patients who all received adjuvant cisplatin and vinorelbine [3].
Endpoint is cancer specific survival.
Results
The combined cisplatin and vinorelbine profiles scored as a continuous covariate showed 1) a Hazard Ratio (HR) of 0.265 ((95% CI:0.079-0.889), p=0.032) in the ACT cohort (sensitive versus resistant), and no significant discrimination in the OBS cohort (HR=1.328 (95% CI:0.46-3.835), p=0.60). A multivariate model adjusted for stage demonstrated significance for ACT (HR=0.284 (95% CI:0.086-0.944), p=0.040) but not for OBS (HR=1.702 (95% CI: 0.575-5.036), p=0.34).
The combined profiles resulted in 2) a significant prediction for up to 3 years from surgery (HR=0.143 (95% CI:0.038-0.542), p=0.004, scored as a continuous covariate). A multivariate model adjusting for stage showed that the predictor remained significant (HR=0.123 (95% CI:0.030-0.512), p=0.004).
A pooled analysis of the two treated cohorts resulted in a significant prediction (HR=0.187, (95% CI:0.069-0.508), p=0.001) up to 3 years from surgery using a random effects model.
Conclusions
The combined profiles demonstrate that NSCLC patients who benefit from cisplatin and vinorelbine can be identified. The profiles did not discriminate patients in the untreated arm. This holds promise for a predictive effect of the profiles and it is currently being validated in a prospective study [4].
[1] PLoS ONE 2016, 11(2): e0148070.
[2] Zhu et al JCO 2010;28:4417-4424.
[3] ASCO 2016 abstract e20007.
[4] AACR 2016 Abstract CT154.
APO010 sensitivity in relapsed Multiple Myeloma patients
A.J. Vangsted1, P.B. Jensen2, M.W. Madsen2, P. Gimsing1, T. Jensen3, A. Hansen3, A. Rasmussen2, A. Nielsen2, U. Buhl2, H. Jandu2, N. Brunner2, B. Pratt2, U.C. Frølund4, C. Helleberg5, N. Abildgaard6, S. Knudsen2
1Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DK, 2Oncology, Oncology Venture, Hørsholm, DK, 3Biology, Medical Prognosis, Scottsdale, AZ, US, 4Haematology, Roskilde Hospital, Roskilde, DK, 5Oncology, University Hospital Herlev, Herlev, DK, 6Haematology, Odense University Hospital, Odense C, DK
Background
Multiple Myeloma is the next most common hematological malignancy and represents a continuous medical challenge since all patients eventually progress despite of many new drugs approved lately. The incidence of Multiple Myeloma is about 6 to 8 out of 100.000 in Western Countries. APO010 (a hexameric FAS-ligand) is an immune-oncology drug, which mimics cytotoxic T-lymphocyte signaling to induce apoptosis and could therefore be a new effective drug for Multiple Myeloma as these cells express CD95 (FAS-receptor).
Methods
Using a previously validated method by Medical Prognosis Insttute A/S (MPI), we have developed an APO010 response predictor (APO010-DRPTM), which is based on gene expression cluster obtained by comparing associations between gene expression profiles and growth inhibition by APO010 in a panel of cell lines. A second step has included filtering the identified gene expression profile against mRNA expression from a collection of 3200 human tumors, thereby making a predictive profile for APO010 responsiveness. We have initiated to screen relapsed/refractory Multiple Myeloma patients by isolating CD138 positive myeloma cells from the bone marrow and perform APO010-DRPTM in order to select the patients with the highest likelihood of benefit from APO010 treatment.
Results
Using the APO010-DRPTM analysis demonstrated Multiple Myeloma to be sensitive to APO010 compared to most solid tumors except breast cancer, which also appeared to be sensitive. First results from Multiple Myeloma patient screening will be presented at ESMO 2016.
Conclusion
Combining APO010 with DRPTM analysis will add a precision medicine element to immune-oncology treatment of Multiple Myeloma. This will enable us to identify patients with high likelihood of response and thereby facilitate focused future trial design and patient recruitment to achieve clinical success.
About the Drug Response Predictor - DRP™ screening tool
Oncology Venture uses the MPI multi gene DRP™ to select those patients that by the gene signature in their cancer is found to have a high likelihood of response to the drug. The goal is to develop the drug for the right patients and by screening patients before treatment the response rate can be significantly increased.
This DRP™ method builds on the comparison of sensitive vs. resistant human cancer cell lines including genomic information from cell lines combined with clinical tumor biology and clinical correlates in a systems biology network. The DRP™ is based on messenger RNA.
About Oncology Venture Sweden AB
Oncology Venture Sweden AB is engaged in the research and development of anti-cancer drugs via its wholly owned Danish subsidiary Oncology Venture ApS. Oncology Venture has a license to use Drug Response Prediction – DRP™ – in order to significantly increase the probability of success in clinical trials. DRP™ has proven its ability to provide a statistically significant prediction of clinical outcomes from drug treatment in cancer patients in 29 of the 37 clinical studies that were examined. The Company uses a model that alters the odds in comparison with traditional pharmaceutical development. Instead of treating all patients with a particular type of cancer, patients’ tumors genes are screened first and only those who are most likely to respond to the treatment will be treated. Via a more well-defined patient group, the risk and costs are reduced while the development process becomes more efficient.
The current product portfolio: LiPlaCis for Breast Cancer, Irofulven developed from a fungus for prostate cancer and APO010 – an immuno-oncology product for Multiple Myeloma.