Development efforts for: DecisionDx-EC
The proprietary DecisionDx-EC test was discovered at The University of Texas M. D. Anderson Cancer Center for the purpose of predicting pathologic response to preoperative chemoradiation therapy in esophageal cancer (EC). The objective of the DecisionDx-EC test is to predict which patients may have a complete pathologic response to preoperative chemoradiation and which patients may be resistant to this regimen. This helps in the design of an optimal personalized treatment regimen.
The DecisionDx-EC test has completed assay development and clinical development. The verification study (n=60) demonstrated high sensitivity and specificity for detection of both the complete pathologic response group and the non-responsive group. The final validation study (n=167) was the focus of an NIH-sponsored grant and was completed in late 2010. Some of this data was presented at the American Society of Clinical Oncology (ASCO) in June, 2011.
We are currently completing the final steps of validation and anticipate having the DecisionDx-EC test available for clinical use in the next three months.
Preliminary data suggests that this assay may have application in other non-esophageal cancers.
Development efforts for: DecisionDx-Melanoma
The proprietary DecisionDx-Melanoma test was discovered at Castle Biosciences for the purpose of predicting distant metastatic risk in patients diagnosed with American Joint Committee on Cancer (AJCC) stage I, II or III cutaneous melanoma. Patients with stage I melanoma have thin tumors, generally less than 1 mm and have a low risk (7 to 14% risk of metastasis at 10 years). Stage II and III melanomas are thicker than stage I melanomas. Patients with stage II melanoma have a sentinel node evaluation that was negative for the presence of melanoma cells. Stage II patients have a higher average risk of metastasis than stage I patients but lower than stage III patients. Stage III patients have a sentinel node evaluation that was positive for the presence of melanoma cells. There is significant overlap in the range of metastatic risk between patients with stage II and stage III. However, today patients with stage I or II melanoma are managed primarily by the dermatologist for local recurrence and development of additional primary melanomas. Patients with stage III melanoma generally receive removal of regional lymph nodes and are offered adjuvant interferon treatment.
To summarize, there are a significant number of patients with stage I or II melanoma who will develop metastatic disease. These patients are treated as group of ‘low risk’ patients despite that individual patients are at ‘high risk’.
Castle Biosciences embarked on a series of collaborative studies beginning in mid-2011 for the purpose of developing a molecular test that would improve identification of stage I and II melanomas that are at high risk of metastasizing. Preliminary data was presented at the American Society of Clinical Oncology in June 2012 (link). While clinical validation has not been completed, this data and subsequent analyses with additional datasets show the DecisionDx-Melanoma test to be accurate in identifying patients with stage I and II melanomas that are at high risk for distant metastasis. Furthermore, these analyses show the test to be superior to AJCC staging and other clinical and pathologic factors such as Breslow’s thickness.
The company is performing the independent clinical validation studies and believes that it is on track to completing the initial studies in the first half of 2013.
Development efforts for BAP1
The role of BAP1 in metastasis in uveal melanoma was recently discovered by Drs. Harbour and Bowcock at Washington University (link). Castle Biosciences exclusively licensed the use of BAP1 in uveal melanoma and cutaneous melanoma from Washington University and is completing development of the technology as a tool for identifying patients who may be responsive to certain treatments as well as inherited risk for risk of uveal melanoma, cutaneous melanoma, mesothelioma and other cancers (so called germ line testing). Castle compared BAP1 testing as a predictor of metastasis in uveal melanoma to their DecisionDx-UM test. The analysis confirmed that the DecisionDx-UM test is superior to BAP1 testing for predicting the risk of metastasis in uveal melanoma. The company also plans to investigate the role of BAP1 in metastasis of other cancers.
Development efforts for: DecisionDx-Mesothelioma
A prognostic test in patients undergoing standard of care surgical resection and differential diagnostic (for mesothelioma vs other thoracic neoplasms) test were discovered, developed, and validated for use in mesothelioma by inventors at Brigham and Women’s Hospital. Castle Biosciences exclusively licensed the intellectual property and technology rights related to these tests from Brigham and Women’s Hospital.
The DecisionDx-Mesothelioma test is technically robust and has been evaluated in a prospective clinical study, achieving level of evidence ”1A” as defined by the National Comprehensive Cancer Network (Febbo, 2011). Level 1A is the highest level of evidence for tumor biomarkers.
As background, mesothelioma disease creates diagnostic and prognostic challenges. Standard of care includes surgical resection with or without adjuvant therapy which is a complex procedure involving significant recovery time. Unfortunately, only some patients experience significant benefit from standard of care interventions. When used alone, or in conjunction with other simple clinical parameters, the DecisionDx-Mesothelioma test can help identify those patients who will most likely benefit from aggressive surgery, as well as assist with further treatment planning.
The company is completing validation and the test should be available in early 2013.