Carolina BioOncology Institute PLLC

United States

Carolina BioOncology Institute PLLC

United States
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BURLINGAME, Calif., Nov. 11, 2016 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, today announced preliminary clinical safety and efficacy data from the dose-selection phase of its ongoing Phase 1/1b study of CPI-444 as a single agent and in combination with Genentech’s Tecentriq® (atezolizumab),‎ a fully humanized monoclonal antibody targeting protein programmed cell death ligand 1 (PD-L1). CPI-444 is a selective and potent inhibitor of the adenosine A2A receptor. The data were presented today in a poster session by John Powderly II, M.D., founder and president of the Carolina BioOncology Institute, at the Society for Immunotherapy of Cancer’s (SITC) 31st Annual Meeting & Associated Programs in National Harbor, Maryland. The poster can be accessed online here. “Although the data is early, we are seeing encouraging evidence of clinical activity with CPI-444 as a monotherapy and in combination with Tecentriq in patients with advanced refractory cancers,” said Richard A. Miller an oncologist and co-founder, president and chief executive officer of Corvus. "We are excited about these preliminary data which show that several patients have achieved stable disease, one of the trial’s primary endpoints, with ongoing responses in cohorts receiving single agent and combination therapy. Tumor regression has been seen in patients who were naïve and refractory to prior treatments with anti-PD-1 or PD-L1 antibodies.” Initial safety and efficacy data from the first 46 patients enrolled in the dose-selection phase of the Phase 1/1b trial with a median follow up of two months were presented at the conference. All patients had failed all approved therapies for their disease, with a median of four prior treatment regimens (range: 1-5). Fifty-two percent of patients were refractory to prior treatment with anti-PD-1/PD-L1 antibodies. Enrolled patients had the following cancers: non-small cell lung (NSCLC), N=10; triple negative breast (TNBC), N=10; bladder, N=6; renal, N=5; melanoma, N=7; colorectal, N=3; prostate, N=2; and head and neck, N=3. The primary endpoints of the study are response rate and duration of clinical benefit (defined as complete response, partial response or stable disease). Patients are treated until disease progression or evidence of grade 3 or 4 toxicity. “The data generated in this trial confirms the value of the protocol design and could provide us with an efficient route to future registration trials of CPI-444, particularly as a monotherapy or in combination with anti-PD1/PD-L1 in patients who are refractory to previous treatment with PD1/PD-L1 antibodies," said Ginna G. Laport, M.D., vice president, Clinical Development, at Corvus. “This initial part of the trial identified the optimum dose of CPI-444 that is being used in the second part of the trial, which is currently enrolling patients.” In a separate poster presentation (available online here), Corvus reported on the effects of treatment with CPI-444 on circulating blood immune cells and T-cell clonality. These results indicate: “The biomarker program is generating a wealth of information and we are encouraged by early data that suggest that CPI-444 treatment results in induction of T-cell mediated immune response in patients,” said Ian McCaffery Ph.D., vice president, Translational Sciences, at Corvus. “Our goal is to understand the mechanisms of action and changes in patient immune status and these data suggest that we may be able to identify biomarkers to help define and identify the patients most likely to respond to CPI-444.” About the Phase 1/1b Trial The Phase 1/1b trial is designed to examine the activity of CPI-444 as a single agent and in combination with Genentech’s Tecentriq (atezolizumab), an anti-PD-L1 antibody. Patients with non-small cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer, colorectal cancer, head and neck cancer, bladder cancer and prostate cancer who have failed all standard therapies are eligible. The first part of the study (dose-selection) included four cohorts of 12 patients each (N=48) – three cohorts treated with single agent CPI-444 (100 mg twice daily for 14 days; 100 mg twice daily for 28 days; 200 mg once daily for 14 days) and one cohort treated with the combination (CPI-444 50 mg or 100 mg twice daily for 14 days combined with Tecentriq). A treatment cycle is 28 days. Based on biomarker analyses showing sustained, complete blockade of the adenosine A2A receptor in peripheral blood lymphocytes, and evidence of immune activation in circulating lymphocytes, an optimum single agent and combination dose of 100 mg twice a day for 28 days was selected. The second part of the study is currently evaluating CPI-444 as a single agent in five disease-specific cohorts, and CPI-444 in combination with Tecentriq in five additional matched disease-specific cohorts. Corvus expects that each of these 10 cohorts will initially enroll 14 patients, but each cohort may be expanded based on efficacy. About Corvus Pharmaceuticals Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company focused on the development and commercialization of small molecule and antibody agents that target the immune system to treat patients with cancer. These agents block or modify crucial immune checkpoints and reprogram immune T-cells. Corvus’ lead product, CPI-444, is a checkpoint inhibitor that is designed to disable a tumor’s ability to subvert attack by the immune system by inhibiting adenosine in the tumor microenvironment. CPI-444 is a small molecule that is taken orally. CPI-444 is currently being evaluated in a multicenter Phase 1/1b clinical trial in patients with various solid tumors. This successive expansion cohort trial is examining the activity of CPI-444 both as a single agent and in combination with Genentech’s Tecentriq (atezolizumab), an anti-PD-L1 antibody. Corvus is conducting the trial with Genentech, a member of the Roche Group, under a clinical trial collaboration the two companies entered into in October 2015. For more information, visit: Forward-Looking Statements This press release contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-444, both as a single agent and in combination with anti-PD-1 or anti-PD-L1, the Company’s ability to develop and advance product candidates into and successfully complete clinical trials, including the Company’s Phase 1/1b clinical trial for CPI-444, the utility of biomarker data collected and the suitability of the dosing regimen selected for the Company’s Phase 1/1b clinical trial for CPI-444. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Form 10-Q for the quarter ended September 30, 2016 filed with the Securities and Exchange Commission on November 3, 2016, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to utilize biomarker data, select a suitable dosing regimen and demonstrate evidence of efficacy and safety for CPI-444 during its Phase 1/1b clinical trial; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete clinical trials; the unpredictability of the regulatory process; regulatory developments in the United States and foreign countries. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Hughes A.D.,Cornell University | Mattison J.,Cornell University | Powderly J.D.,BioCytics Inc | Powderly J.D.,Carolina BioOncology Institute PLLC | And 3 more authors.
Journal of Visualized Experiments | Year: 2012

Circulating tumor cells (CTC) are cells that disseminate from a primary tumor throughout the circulatory system and that can ultimately form secondary tumors at distant sites. CTC count can be used to follow disease progression based on the correlation between CTC concentration in blood and disease severity 1. As a treatment tool, CTC could be studied in the laboratory to develop personalized therapies. To this end, CTC isolation must cause no cellular damage, and contamination by other cell types, particularly leukocytes, must be avoided as much as possible 2. Many of the current techniques, including the sole FDA-approved device for CTC enumeration, destroy CTC as part of the isolation process (for more information see Ref. 2). A microfluidic device to capture viable CTC is described, consisting of a surface functionalized with E-selectin glycoprotein in addition to antibodies against epithelial markers 3. To enhance device performance a nanoparticle coating was applied consisting of halloysite nanotubes, an aluminosilicate nanoparticle harvested from clay 4. The E-selectin molecules provide a means to capture fast moving CTC that are pumped through the device, lending an advantage over alternative microfluidic devices wherein longer processing times are necessary to provide target cells with sufficient time to interact with a surface. The antibodies to epithelial targets provide CTC-specificity to the device, as well as provide a readily adjustable parameter to tune isolation. Finally, the halloysite nanotube coating allows significantly enhanced isolation compared to other techniques by helping to capture fast moving cells, providing increased surface area for protein adsorption, and repelling contaminating leukocytes 3,4. This device is produced by a straightforward technique using off-the-shelf materials, and has been successfully used to capture cancer cells from the blood of metastatic cancer patients. Captured cells are maintained for up to 15 days in culture following isolation, and these samples typically consist of >50% viable primary cancer cells from each patient. This device has been used to capture viable CTC from both diluted whole blood and buffy coat samples. Ultimately, we present a technique with functionality in a clinical setting to develop personalized cancer therapies. © 2012 Creative Commons Attribution-NonCommercial License.

Greene B.T.,BioCytics Inc. | Greene B.T.,Carolina BioOncology Institute PLLC | Hughes A.D.,Cornell University | King M.R.,Cornell University
Frontiers in Oncology | Year: 2012

Circulating tumor cells (CTCs) are believed to be responsible for the development of metastatic disease. Over the last several years there has been a great interest in understanding the biology of CTCs to understand metastasis, as well as for the development of companion diagnostics to predict patient response to anti-cancer targeted therapies. Understanding CTC biology requires innovative technologies for the isolation of these rare cells. Here we review several methods for the detection, capture, and analysis of CTCs and also provide insight on improvements for CTC capture amenable to cellular therapy applications. © 2012 Greene, Hughes and King.

Hughes A.D.,Cornell University | Marshall J.R.,Cornell University | Keller E.,BioCytics Inc | Keller E.,Carolina BioOncology Institute PLLC | And 5 more authors.
Cancer Letters | Year: 2014

Personalized medicine holds great promise for cancer treatment, with the potential to address challenges associated with drug sensitivity and interpatient variability. Circulating tumor cells (CTC) can be useful for screening cancer drugs as they may reflect the severity and heterogeneity of primary tumors. Here we present a platform for rapidly evaluating individualized drug susceptibility. Treatment efficacy is evaluated directly in blood, employing a relevant environment for drug administration, and assessed by comparison of CTC counts in treated and control samples. Multiple drugs at varying concentrations are evaluated simultaneously to predict an appropriate therapy for individual patients. © 2013 The Authors.

Hughes A.D.,Cornell University | Mattison J.,Cornell University | Western L.T.,Cornell University | Powderly J.D.,Bio Cytics Inc. | And 4 more authors.
Clinical Chemistry | Year: 2012

BACKGROUND: Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage. METHODS: We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer. RESULTS: Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20-704 viable CTCs per 3.75-mL sample, achieving purities of 18%-80% CTCs. The nanotubecoated surface significantly improved capture purities (P < 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading. CONCLUSIONS: The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies. © 2012 American Association for Clinical Chemistry.

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