Replies to post #130874 on Biotech Values

[zipjet]

http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=33102e2e-3ef3-4fba-b02b-ed79dd34ea39&cKey=710f0196-24bb-4c82-a5fd-b324760072f8&mKey=%7bA57FF86D-D414-4079-BCBD-157746574F37%7d

Abstract Number: B114
Presentation Title: Cabozantinib effects on bone metastasis: Computer-aided quantitative bone scan assessment of prostate cancer treatment response
Location: West Hall, Level One, Moscone Center West
Poster Board Number: B114
Author Block: Matthew S. Brown1, Gregory H. Chu2, Hyun Jung (Grace) Kim2, Martin A. Auerbach3, Cheryce Poon2, Adria Vidovic4, Bharath Ramakrishna2, David W. Gjertson2, Howard I. Scher5, Jonathan G. Goldin1, Matthew R. Smith6. 1Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, University of California & MedQIA, LLC, Los Angeles, CA; 2Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, University of California, Los Angeles, CA; 3Department of Nuclear Medicine, University of California, Los Angeles, CA; 4MedQIA LLC, Los Angeles, CA; 5Memorial Sloan-Kettering Cancer Center, New York, NY; 6Massachusetts General Hospital Cancer Center, Boston, MA
Abstract Body: Background: Cabozantinib is an oral inhibitor of MET and VEGFR2 and at a dose of 100 mg qd has demonstrated high rates of partial or complete bone scan resolution in CRPC patients with bone metastases, as assessed by manual visual reads. No accepted approach exists for the assessment of bone scan response in prostate cancer patients. An FDA 510(k) approved image analysis package has been developed that includes a computer-aided detection (CAD) system to detect pixels associated with bone lesions on bone scan with high accuracy, thus facilitating quantitative assessment of tumor burden with advantages of objectivity and consistency over manual approaches. A change in total Bone Scan Lesion Area of 30% or greater has been previously established as a cutoff point to distinguish responders from non-responders [1].
Methods: Original Digital Imaging and Communications in Medicine (DICOM) format images of baseline and week 6 bone scan assessments were collected and analyzed by the automated CAD system then reviewed by a physician experienced with bone scan interpretation as part of an ongoing clinical study of single agent cabozantinib at a lower starting dose of 40 mg qd in CRPC subjects with evidence of bone metastases. All subjects had undergone standard of care whole body scintigraphy, 2-4 hours post-injection of 20-25 mCi of Tc MDP. All images underwent intensity normalization to a bone scan reference to account for differences in radiotracer dosing levels and scan timing to improve reproducibility. Lesions consistent with metastatic foci of disease were automatically segmented based on anatomic region-specific intensity thresholds. Each segmented image was reviewed by a nuclear medicine physician for removal of any remaining false positive regions (e.g. areas of degenerative joint disease). Quantitative assessment of lesion burden was then determined.
Results: 10 CRPC subjects showing evidence of bone metastasis were treated in an ongoing dose-ranging study with cabozantinib and were evaluable for bone scan response assessment at week 6. Reductions in the following parameters (median and range) were observed at week 6 relative to baseline: total Bone Scan Lesion Area (168.5 cm2 [20, 864] to 54 cm2 [0, 431]; 68% reduction, Bone Scan Lesion Count (34 [3, 74] to 3 [0, 64]; 91% reduction), and mean normalized Bone Scan Lesion Intensity (92.2 [56.5, 155.0] to 57.0 [0, 90.5]; 38% reduction). All 10 subjects had a reduction in Bone Scan Lesion Area, with 9 achieving a bone scan response at the week 6 timepoint as assessed by both the CAD system and visual review by the investigator.
Conclusion: A significant reduction in apparent bone scan abnormality was demonstrated by the automated CAD system. The results demonstrate the potential for objective measurement of cabozantinib treatment effects in bone, laying the foundation for further validation against other clinically relevant outcome measures such as pain and overall survival.
[1] G. H. Chu, M. S. Brown, H. J. Kim, M. Auerbach, C. Poon, B. Ramakrishna, A. Vidovic, D. W. Gjertson, M. J. Morris, S. M. Larson, J. G. Goldin, H. I. Scher. Initial analytic validation of automated bone scan measures for treatment response assessment in patients with metastatic castration-resistant prostate cancer (CRPC). J Clin Oncol 29: 2011 (suppl; abstr e15174).

[DewDiligence]

EXEL question:

“Eleven patients were evaluable at Week 6, of which 10 had bone scan responses… Eight of the 10 responding patients had a confirmation of the bone scan response at week 12…”

Is it known whether the other 2 patients among the 10 responders had a follow-up scan?

[mcbio]

EXEL - signs cabo CRADA

http://finance.yahoo.com/news/Exelixis-Signs-CRADA-With-bw-280609808.html?x=0

Exelixis Signs CRADA With National Cancer Institute to Expand Development Plan of Cabozantinib

NCI to send mass solicitation letter to investigators requesting proposals to evaluate cabozantinib across multiple solid tumor indications in pediatric and adult patients

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Exelixis, Inc. (Nasdaq: EXEL - News) today announced that it has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute’s Cancer Therapy Evaluation Program (CTEP) for further evaluation of cabozantinib, Exelixis’ lead compound, in a variety of solid tumors. Cabozantinib is a potent, dual inhibitor of MET and VEGFR2. Exelixis recently announced positive phase 3 data in the EXAM trial in medullary thyroid cancer and that the company is initiating pivotal phase 3 trials in castration-resistant prostate cancer.

The agreement covers up to twenty active clinical trials per year over the lifetime of the CRADA. Under the terms of the CRADA, Exelixis and the National Cancer Institute (NCI) will undertake a series of clinical trials to evaluate the safety and efficacy of cabozantinib in several cancers based upon encouraging anti-tumor activity observed in earlier studies. The trials will be designed to address a number of scientific questions such as how the efficacy of cabozantinib compares with other VEGFR2 inhibitors, the ability of cabozantinib to overcome resistance of tumors to VEGFR2 or EGFR inhibition, and the mechanism of activity of cabozantinib in tumors metastatic to bone.

As data from the CTEP-sponsored studies and other Exelixis-sponsored trials emerge, the NCI and Exelixis will discuss additional trials to complement and support the development of cabozantinib. The NCI may also support non-clinical studies that focus on identifying assays for monitoring the biologic activity of cabozantinib, as well as combination studies of the compound with other targeted agents. Any additional studies will be with mutual agreement and approval of both parties.

“Our CRADA with the NCI’s Division of Cancer Treatment and Diagnosis reinforces our commitment to maximize the broad clinical potential of cabozantinib in a wide variety of tumor indications while focusing our own internal efforts on prostate and thyroid cancer,” said Michael M. Morrissey, PhD, Exelixis’ president and chief executive officer. “As we prepare to file our new drug application with the FDA for the medullary thyroid cancer indication, and continue to advance our pivotal trial plans in prostate cancer, we have found an exemplary partner in the NCI to drive clinical research in other key areas. We hope the CTEP collaboration will provide additional clinical data that will highlight cabozantinib’s differentiated clinical profile in multiple different cancer indications.”

About Cabozantinib

Cabozantinib is a potent, dual inhibitor of MET and VEGFR2. Cabozantinib is an investigational agent that provides coordinated inhibition of metastasis and angiogenesis to kill tumor cells while blocking their escape pathways. The therapeutic role of cabozantinib is currently being investigated across several tumor types. MET is upregulated in many tumor types, thus facilitating tumor cell escape by promoting the formation of more aggressive phenotypes, resulting in metastasis. MET-driven metastasis may be further stimulated by hypoxic conditions in the tumor environment, which are often exacerbated by selective VEGF-pathway inhibitors. In preclinical studies, cabozantinib has shown powerful tumoricidal, antimetastatic and antiangiogenic effects, including:

• Extensive apoptosis of malignant cells
• Decreased tumor invasiveness and metastasis
• Decreased tumor and endothelial cell proliferation
• Blockade of metastatic bone lesion progression
• Disruption of tumor vasculature

About Exelixis

Exelixis, Inc. is a biotechnology company committed to developing small molecule therapeutics for the treatment of cancer. Exelixis is focusing its proprietary resources and development efforts exclusively on cabozantinib, its most advanced solely-owned product candidate, in order to maximize the therapeutic and commercial potential of this compound. Exelixis believes cabozantinib has the potential to be a high-quality, differentiated pharmaceutical product that can make a meaningful difference in the lives of patients. Exelixis has also established a portfolio of other novel compounds that it believes have the potential to address serious unmet medical needs. For more information, please visit the company's web site at www.exelixis.com.