On October 10, 2016 Genomic Health, Inc. (Nasdaq: GHDX) reported results from eight Oncotype DX Breast Recurrence Score (RS) presentations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark, highlighting superior clinical evidence in identifying which patients with node-negative and node-positive invasive breast cancer should be treated with chemotherapy (Press release, Genomic Health, OCT 10, 2016, View Source [SID:SID1234515720]). Specifically, prospective clinical outcomes in more than 7,400 patients with node-positive invasive breast cancer from two independent studies show excellent survival in women with RS results less than 18.

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"The ESMO (Free ESMO Whitepaper) presentations continue to reinforce that Oncotype DX provides unique and unsurpassed value beyond tumor size and tumor grade for invasive breast cancer patients with node-negative and certain patients with node-positive disease," said Steven Shak, M.D., chief scientific officer, Genomic Health. "With our level 1 evidence for predicting chemotherapy benefit and prospective outcomes now in over 63,000 patients from the TAILORx, Clalit, PlanB and SEER studies, it is clear that Oncotype DX is the only genomic test that can provide doctors with confidence that their patients will receive the quality care they deserve."

New data confirm Oncotype DX accurately predicts clinical outcomes in node-positive breast cancer patients
Two independent studies in more than 7,400 patients from the United States and Israel provide further evidence that Oncotype DX accurately predicts outcomes in patients with early-stage, node-positive invasive breast cancer. Specifically, an updated analysis of the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) Registry results from 6,768 patients who were treated based on RS results showed that in 3,919 patients with a RS of less than 18, breast cancer specific survival was excellent. Specifically, it was greater than 97 percent in patients with micrometastases, one, or two positive lymph nodes.

Similarly, results from a prospective study of more than 700 patients tested with Oncotype DX within Clalit Health Services, the largest health maintenance organization in Israel, showed that patients with micrometastases or one to three positive lymph nodes and a RS less than 18, the vast majority (92.9 percent) of whom were treated with hormonal therapy alone, had very good outcomes with low rates of distant recurrence (3.2 percent) and excellent breast cancer survival ( > 99 percent) at five years.

"These two important updates add significantly to the growing body of evidence that Oncotype DX accurately predicts outcomes and aids treatment decision making in women with early-stage, node-positive breast cancer. Just as we have learned in node-negative disease, it is now increasingly evident that women with one to three positive nodes and the lower scores do extremely well without chemotherapy," said Kathy S. Albain, MD, FACP, FASCO, professor of medicine, Loyola University Chicago, Cardinal Bernardin Cancer Center, Maywood, IL. "While we are now completing accrual of the RxPONDER trial looking at whether chemotherapy adds to standard endocrine therapy in this group, getting the results will take several years. In the meantime, these data along with previously published results, provide extremely strong evidence to justify use of Oncotype DX in 1-3 node-positive disease. If the patient’s tumor biology is that of a low Recurrence Score, chemotherapy simply does not add benefit, and its risks and costs can be avoided."

In addition, exploratory analyses of patients with RS results of 18 to 30 showed that the rate of distant recurrence were generally closer to lower risk patients with a RS less than 18. The group of patients with mid-range Recurrence Score results is also being studied in the Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, and the RxPONDER trial.

Oral presentation of additional SEER analysis reveals large disparities in survival and Oncotype DX testing in older patients
Following up on the results of the multinational TEAM study, which reported worse outcomes for older patients with hormone-receptor-positive (HR+) breast cancer, this study examined RS results in patients 70 years and older versus those under 70 years. The results showed that mortality was indeed much higher in older patients who were either not tested with Oncotype DX or had a RS result greater than 18. Patients age 70 or older also had lower reported chemotherapy use, supporting continued examination of the often reported issue of under-treatment of the elderly.

Oncotype DX reduces overtreatment of breast cancer and increases confidence in treatment decisions globally
Results from multiple international studies conducted in Canada, the Czech Republic, Italy and Spain reinforce the findings of more than 20 previous decision impact studies from around the world. Collectively, the results demonstrated that the RS increases confidence in treatment decisions and changes approximately 30 percent of treatment recommendations, resulting in a 22-24 percent reduction in use of chemotherapy in patients, including in those with node-positive disease.

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. With more than 600,000 patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeDX.com, www.mybreastcancertreatment.org and www.myprostatecancertreatment.org.

On October 10, 2016 Exelixis, Inc. (NASDAQ:EXEL) reported detailed results from the CABOSUN randomized phase 2 trial of cabozantinib in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) (Press release, Exelixis, OCT 10, 2016, View Source;p=RssLanding&cat=news&id=2210335 [SID:SID1234515689]). Principal investigator Toni K. Choueiri, M.D. will present detailed data from late-breaking CABOSUN abstract [#LBA30_PR] today in the Presidential Symposium 3 session, starting at 16:30 CEST (local Copenhagen time) / 10:30 a.m. EDT / 7:30 a.m. PDT at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016, which is being held October 7 – 11, 2016 in Copenhagen.

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CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP).

In CABOSUN, with a median follow-up of 20.8 months, cabozantinib demonstrated a clinically meaningful and statistically significant 31 percent reduction in the rate of disease progression or death [HR 0.69, 95% CI (0.48-0.99), one-sided P=0.012]. The median progression-free survival (PFS) for cabozantinib was 8.2 months versus 5.6 months for sunitinib, corresponding to a 2.6 months (46 percent) improvement favoring cabozantinib over sunitinib. PFS benefits were independent of IMDC risk group (intermediate or poor risk) and presence or absence of bone metastases at baseline. The results for sunitinib were in line with a previously published retrospective analysis of 1,174 intermediate- and poor-risk RCC patients from the IMDC database, which documented a median PFS of 5.6 months with a first-line targeted therapy, mainly sunitinib, in this patient population.1

Objective response rate (ORR) was also significantly improved, at 46 percent (95% CI 34% – 57%) for cabozantinib versus 18 percent (95% CI 10% to 28%) for sunitinib. With a median follow up of 22.8 months, median overall survival was 30.3 months for cabozantinib versus 21.8 months for sunitinib [HR 0.80, 95% CI (0.50 – 1.26)].

"The results presented today support the potential of cabozantinib to become a new therapeutic option for previously untreated patients following their diagnosis with advanced kidney cancer," said Toni K. Choueiri, M.D., Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and chair of the CABOSUN study. "Not only has cabozantinib surpassed sunitinib, the current standard of care, in progression-free survival and objective response rate, cabozantinib’s effects on progression-free survival were also consistently favorable across patient stratification subgroups including IMDC intermediate versus poor-risk groups and presence or absence of bone metastases."

"We at the Alliance for Clinical Trials in Oncology are pleased that CABOSUN has successfully demonstrated that cabozantinib has the potential to benefit patients with advanced renal cell carcinoma as a first-line therapy," said Michael J. Morris, M.D., Associate Member at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary Committee. "We are grateful to everyone who has participated in the trial, especially the physicians, patients and their families."

Based on these results, Exelixis plans to submit a Supplemental New Drug Application (sNDA) for cabozantinib as a treatment of first-line advanced renal cell carcinoma, and is working with the Alliance to transfer the complete CABOSUN clinical database to Exelixis.

"The past year has seen a tremendous level of progress in the treatment of kidney cancer, and we are excited to be at the forefront of bringing these advancements to patients," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "Patients in the first-line setting with either intermediate- or poor-risk disease progress rapidly with sunitinib, a current standard of care; therefore, there is a clear need for new options that provide improved clinical benefit in this difficult to treat patient population. To that end, based on the CABOSUN results, we are planning to submit a supplemental New Drug Application in the United States for cabozantinib as a first-line treatment for advanced renal cell carcinoma."

CABOSUN enrolled 157 patients with previously untreated advanced RCC: 80.9 percent of patients were intermediate risk per IMDC criteria and 19.1 percent were poor risk, 36.3 percent of patients had bone metastases, 46 percent of patients had ECOG Performance Status (PS) 0, 41 percent had ECOG PS 1, and 13 percent had ECOG PS 2. All patients were included in the efficacy analyses that followed the intent-to-treat principle. Tumor assessments were performed by the investigators following RECIST criteria. At the time of the analysis of the primary endpoint of PFS, the median duration of treatment in CABOSUN was 6.9 months with cabozantinib and 2.8 months with sunitinib; 13 patients continued on cabozantinib treatment versus 2 patients on sunitinib treatment. Dose reductions occurred for 58 percent and 49 percent of patients, respectively. Discontinuation rate due to an adverse event was 20 percent with cabozantinib and 21 percent with sunitinib.

One hundred and fifty patients were evaluable for safety. Ninety-nine percent of patients on both arms experienced at least one adverse event. The most common all causality grade 3 or 4 adverse events observed in more than 5 percent of patients were hypertension (28 percent), diarrhea (10 percent), palmar-plantar erythrodysesthesia (8 percent), and fatigue (6 percent) in the cabozantinib arm, and hypertension (22 percent), fatigue (15 percent), diarrhea and thrombocytopenia (both 11 percent), and oral mucositis (6 percent) in the sunitinib arm. Treatment-related grade 5 events occurred in three patients in the cabozantinib arm (acute kidney injury, sepsis and jejunal perforation) and two patients in the sunitinib arm (sepsis and vascular disorder).

About the CABOSUN Study

On May 23, 2016, Exelixis announced that CABOSUN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC. CABOSUN is being conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP).

CABOSUN was a randomized, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival and objective response rate. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and had to be intermediate or poor risk per the IMDC criteria (Heng, JCO, 2009). Prior systemic treatment for RCC was not permitted.

Please see Important Safety Information below and full U.S. prescribing information at View Source

Webcast for the Financial Community and Media

Exelixis and its partner Ipsen will jointly host a live webcast today, Monday, October 10. The webcast will begin at 19:00 CEST (local Copenhagen time) / 1:00 p.m. EDT / 10:00 a.m. PDT. During the webcast, Exelixis and Ipsen management and invited guest speakers will review and provide context of the results from the CABOSUN study, along with the other data sets on cabozantinib presented at the conference.

To access the webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under Investors & Media. Please connect to the company’s website at least 15 minutes prior to the webcast to ensure adequate time for any software download that may be required to view the program. To listen to an audio-only version of the program by phone, please dial 855-299-5224 (domestic) or 631-267-4890 (international/toll dial) and use passcode 234-026-024. An archived replay of the webcast will be available on the Event Calendar page under Investors & Media at www.exelixis.com after the event concludes.

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2016 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.2 Clear cell RCC is the most common type of kidney cancer in adults.3 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.1 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment.4

The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7-10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

About CABOMETYX (cabozantinib)

CABOMETYX is the tablet formulation of cabozantinib. Its targets include MET, AXL and VEGFR-1, -2 and -3. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

CABOMETYX is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On April 25, 2016, the FDA approved CABOMETYX tablets for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy. On September 9, 2016, the European Commission approved CABOMETYX tablets for the treatment of advanced renal cell carcinoma in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan.

U.S. Important Safety Information

Hemorrhage: Severe hemorrhage occurred with CABOMETYX. The incidence of Grade ≥3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.

Gastrointestinal (GI) Perforations and Fistulas: Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. GI perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.

Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.

Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of everolimus-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.

Diarrhea: Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to diarrhea occurred in 26% of patients.

Palmar-Plantar Erythrodysesthesia Syndrome (PPES): Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-fetal Toxicity: CABOMETYX can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, and constipation.

Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.

Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.

Reproductive Potential: Contraception―Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the final dose. Infertility ―CABOMETYX may impair fertility in females and males of reproductive potential.

Hepatic Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

Please see full Prescribing Information at View Source

On October 10, 2016 NOXXON Pharma N.V. (Paris:ALNOX) a clinical-stage biopharmaceutical company primarily focused on cancer treatment, reported that it presented data yesterday at the ESMO (Free ESMO Whitepaper) conference in Copenhagen, Denmark, studying the role of CXCL12 inhibition by NOX-A12 (olaptesed pegol) in tumor stroma spheroids, a preclinical model that mimics the complexity of the tumor microenvironment (Press release, NOXXON, OCT 10, 2016, View Source [SID:SID1234515721]). These studies showed that NOX-A12 synergizes with therapies working through either T cells or NK cells. Further studies of NOX-A12 with agents working through T-cells such as checkpoint inhibitors or CAR-T cells as well as NK cell-based therapies are warranted.

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Poster Title: CXCL12 Inhibition with NOX-A12 (Olaptesed Pegol) Increases T and NK Cell Infiltration and Synergizes with Immune Checkpoint Blockade and ADCC in Tumour-Stroma Spheroids
Authors: Dirk Zboralski, Anna Kruschinski, Dirk Eulberg and Axel Vater
Location & time: ESMO (Free ESMO Whitepaper) Congress 2016, Copenhagen, Denmark, 7-11 October 2016, Session Immunotherapy of cancer: Abstract #1083P, Hall E, Sunday, 9 October 2016, 13:00 – 14:00

The poster may be downloaded from the company’s website:
www.noxxon.com/downloads/poster/ESMO2016.pdf

NOX-A12, which inhibits the key tumor microenvironment chemokine CXCL12, may be a key partner for a wide range of IO (immuno-oncology) agents. NOXXON has generated promising pre-clinical and clinical data, including recent animal data showing synergy with a checkpoint inhibitor as well as recent phase 2a trials in multiple myeloma and a second hematological cancer that showed a safety profile that supports further development and first signs of efficacy. The company believes that additional clinical trials are warranted to investigate combinations of NOX-A12 multiple classes of IO agents including those acting on or through T-cells and NK cells.

On October 10, 2016 OncoResponse, an immuno-oncology antibody discovery company, reported that it has raised $7 million in a supplemental Series A financing, consisting of a $3.5 million investment from GreatPoint Ventures and a $3.5 million investment from the Helsinn Investment Fund (Press release, OncoResponse, OCT 10, 2016, View Source [SID1234522898]).

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In October 2015, OncoResponse secured $9.5 million as part of an initial closing of its Series A financing co-led by ARCH Venture Partners, Canaan Partners and MD Anderson, with William Marsh Rice University and Alexandria Real Estate Equities also participating. An additional $3 million investment by Baxalta (now Shire) in May 2016, along with the recent investments by GreatPoint and Helsinn, bring the total Series A financing to $19.5 million, which will be used to support OncoResponse’s ongoing efforts to interrogate the humoral response of elite responders to cancer immunotherapy to identify antibodies and potential targets for novel therapeutic development.

OncoResponse utilizes a clinically validated platform technology to rapidly screen antibodies made by the human immune system and identify those with exceptional reactivity to cancer immunotherapy. The company has an ongoing strategic alliance with the MD Anderson Cancer Center, which provides access to patient samples and oncology and translational medicine expertise including clinical and regulatory input.

"We are pleased to welcome GreatPoint and Helsinn Investment Fund to our solid team of investors," said Clifford J. Stocks, CEO of OncoResponse. "These additional funds will support the continued progression of our research programs that aim to identify therapeutically relevant antibodies from patients with elite response to cancer immunotherapy in a number of oncology indications."

"OncoResponse is using innovative technology to develop a deeper understanding of the immune response to cancer immunotherapy," said Andrew Perlman, Co-Founder and Managing Partner of GreatPoint Ventures. "At GreatPoint, we look for companies with uniquely advantaged approaches to solving frustrating problems, and OncoResponse’s pioneering approach to novel target and antibody discovery from elite responders is directly in line with our investment strategy."

"This investment is an excellent example of Helsinn’s focus on early-stage investments in areas of high unmet patient need," said Roberto De Ponti, Pharm.D., Head of Corporate New Ventures and Strategic Investments at Helsinn International Services. "We are proud to be able to support OncoResponse in its mission to address an unmet medical need in patients who are partial or non-responders and expand the promise of immunotherapy.

On October 10, 2016 Pfizer Inc. (NYSE:PFE) reported results from the Phase 3 S-TRAC clinical trial (Sunitinib Trial as Adjuvant Treatment of Renal Cancer) investigating SUTENT (sunitinib) as adjuvant therapy (Press release, Pfizer, OCT 10, 2016, View Source [SID:SID1234515691]). The trial showed SUTENT extended disease-free survival (DFS) by more than one year versus placebo in patients who were at high risk for recurrence after surgical resection of renal cell carcinoma (RCC) (HR 0.761; P=0.030 [95% CI: 0.594-0.975]). These results will be presented today during a Presidential Symposium (Abstract #LBA11_PR) at the ESMO (Free ESMO Whitepaper) 2016 Congress, the annual meeting of the European Society for Medical Oncology being held in Copenhagen, Denmark. The results have also been published online by The New England Journal of Medicine.

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Adjuvant therapies are treatments that can be given to reduce the likelihood of the cancer returning after initial treatment such as surgery.

"We are encouraged by the S-TRAC results because this is the first clinical trial to show increased disease-free survival in the adjuvant setting for RCC," said lead investigator Alain Ravaud, M.D., Ph.D., CHU de Bordeaux Hôpital Saint André. "These data are promising for RCC patients as there are no effective treatments currently available in this setting."

The results from the S-TRAC trial showed that after one year of treatment, the median time until disease recurrence in participants treated with SUTENT after surgery was 6.8 years compared with 5.6 years for patients treated with placebo as assessed by independent central review, resulting in an overall risk reduction of 24 percent. At the time of the analysis, overall survival (OS) data was immature.

Based on the results of S-TRAC, Pfizer is in discussions with global regulatory authorities to determine potential next steps.

"For the past 10 years, Pfizer has been a leader in developing new treatments for patients with kidney cancer, and SUTENT has been the most widely prescribed first line treatment for thousands of patients with advanced RCC around the world," said Mace Rothenberg, MD, Chief Development Officer, Oncology, Pfizer Global Product Development. "The results of S-TRAC suggest that SUTENT has the potential to extend this benefit by reducing the risk of recurrence in patients who have undergone complete surgical removal of their kidney cancer and are at high risk of cancer recurrence."

The adverse events seen in the trial were consistent with SUTENT’s known safety profile. The most common adverse reactions (>20%) are fatigue, asthenia, and fever. Grade ≥3 adverse events were more frequent with SUTENT (62.1%) vs. placebo (21.1%). No deaths occurred due to treatment toxicity.

SUTENT is an oral cancer medication that was first approved in the United States in 2006 for the treatment of advanced RCC. It is currently approved in 119 countries.i Worldwide more than 250,000 patients across diagnoses have been treated with SUTENT in its approved indications of advanced RCC, imatinib-resistant or -intolerant gastrointestinal stromal tumors (GIST) and advanced pancreatic neuroendocrine tumors (pNET).ii SUTENT is not approved in the adjuvant setting.

About Renal Cell Carcinoma (RCC)

Each year, approximately 338,000 new cases of kidney cancer are diagnosed worldwide, representing approximately 2-3 percent of all cancers.iii Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for around 90 percent of cases.iv

About S-TRAC

The S-TRAC trial was a randomized double-blind Phase 3 trial of adjuvant SUTENT vs. placebo in 615 patients with local, resected RCC at high risk of recurrence. Patients received 50 mg/d of SUTENT or placebo in a four weeks on, two weeks off schedule for one year until disease recurrence, occurrence of secondary malignancy, significant toxicity or consent withdrawal. The primary objective was to demonstrate an improvement in DFS by blinded independent central radiologic review. DFS was defined as the time interval from the date of randomization to the first date of recurrence or the occurrence of a secondary malignancy or death. Recurrence referred to relapse of the primary tumor locally or at metastatic sites. The S-TRAC trial has two cohorts: Global and China. These results are from the Global cohort only. Results from the China cohort are not yet mature and will be reported at a later date.

About SUTENT (sunitinib malate)

SUTENT is an oral multi-kinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Two important SUTENT targets, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) are expressed by many types of solid tumors and are thought to play a crucial role in angiogenesis, the process by which tumors acquire blood vessels, oxygen and nutrients needed for growth. SUTENT also inhibits other targets important to tumor growth, including KIT, FLT3 and RET.

SUTENT is indicated for the treatment of advanced renal cell carcinoma (RCC), gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate, and progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease.

SUTENT Important Safety Information

Boxed Warning/Hepatotoxicity: Hepatotoxicity has been observed in clinical trials and post-marketing experience. This hepatotoxicity may be severe, and deaths have been reported. Monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. SUTENT should be interrupted for Grade 3 or 4 drug-related hepatic adverse events and discontinued if there is no resolution. Do not restart SUTENT if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure.

Pregnancy: Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant.

Nursing mothers: Given the potential for serious adverse reactions (ARs) in nursing infants, a decision should be made whether to discontinue nursing or SUTENT.

Cardiovascular events: Cardiovascular events, including heart failure, cardiomyopathy, myocardial ischemia, and myocardial infarction, some of which were fatal, have been reported. Use SUTENT with caution in patients who are at risk for, or who have a history of, these events. Monitor patients for signs and symptoms of congestive heart failure (CHF) and, in the presence of clinical manifestations, discontinuation is recommended. Patients who presented with cardiac events, pulmonary embolism, or cerebrovascular events within the previous 12 months were excluded from clinical studies.

QT interval prolongation and Torsades de Pointes: SUTENT has been shown to prolong QT interval in a dose-dependent manner, which may lead to an increased risk for ventricular arrhythmias including Torsades de Pointes, which has been seen in <0.1% of patients. Monitoring with on-treatment electrocardiograms and electrolytes should be considered.

Hypertension: Hypertension may occur. Monitor blood pressure and treat as needed with standard antihypertensive therapy. In cases of severe hypertension, temporary suspension of SUTENT is recommended until hypertension is controlled.

Reversible posterior leukoencephalopathy syndrome (RPLS): There have been (<1%) reports, some fatal, of subjects presenting with seizures and radiological evidence of RPLS.

Hemorrhagic events: Hemorrhagic events, including tumor-related hemorrhage such as pulmonary hemorrhage, have occurred. Some of these events were fatal. Perform serial complete blood counts (CBCs) and physical examinations.

Tumor lysis syndrome (TLS): Cases of TLS have been reported primarily in patients with high tumor burden. Monitor these patients closely and treat as clinically indicated.

Thrombotic microangiopathy (TMA): TMA, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, sometimes leading to renal failure or a fatal outcome, has been reported in patients who received SUTENT as monotherapy and in combination with bevacizumab. Discontinue SUTENT in patients developing TMA. Reversal of the effects of TMA has been observed after treatment was discontinued.

Proteinuria: Proteinuria and nephrotic syndrome have been reported. Some of these cases have resulted in renal failure and fatal outcomes. Perform baseline and periodic urinalysis during treatment, with follow-up measurement of 24-hour urine protein as clinically indicated. Interrupt SUTENT and dose reduce if 24-hour urine protein is ≥3 g; discontinue SUTENT in cases of nephrotic syndrome or repeat episodes of urine protein ≥3 g despite dose reductions.

Dermatologic toxicities: Severe cutaneous reactions have been reported, including cases of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), some of which were fatal. If signs or symptoms of EM, SJS, or TEN are present, SUTENT treatment should be discontinued. If a diagnosis of SJS or TEN is suspected, treatment must not be re-started. Necrotizing fasciitis, including fatal cases, has been reported, including of the perineum and secondary to fistula formation. Discontinue SUTENT in patients who develop necrotizing fasciitis.

Thyroid dysfunction: Thyroid dysfunction may occur. Monitor thyroid function in patients with signs and/or symptoms of thyroid dysfunction, including hypothyroidism, hyperthyroidism, and thyroiditis, and treat per standard medical practice.

Hypoglycemia: SUTENT has been associated with symptomatic hypoglycemia, which may result in loss of consciousness or require hospitalization. Reductions in blood glucose levels may be worse in patients with diabetes. Check blood glucose levels regularly during and after discontinuation of SUTENT. Assess whether anti-diabetic drug dosage needs to be adjusted to minimize the risk of hypoglycemia.

Osteonecrosis of the jaw (ONJ): ONJ has been reported. Consider preventive dentistry prior to treatment with SUTENT. If possible, avoid invasive dental procedures, particularly in patients receiving bisphosphonates.

Wound healing: Cases of impaired wound healing have been reported. Temporary interruption of therapy with SUTENT is recommended in patients undergoing major surgical procedures.

Adrenal function: Adrenal hemorrhage was observed in animal studies. Monitor adrenal function in case of stress such as surgery, trauma, or severe infection.

Laboratory tests: CBCs with platelet count and serum chemistries including phosphate should be performed at the beginning of each treatment cycle for patients receiving treatment with SUTENT.

CYP3A4 coadministration: Dose adjustments are recommended when SUTENT is administered with CYP3A4 inhibitors or inducers. During treatment with SUTENT, patients should not drink grapefruit juice, eat grapefruit, or take St John’s Wort.

Most common ARs & most common grade 3/4 ARs (advanced RCC): The most common ARs occurring in ≥20% of patients receiving SUTENT for treatment-naïve metastatic RCC (all grades, vs IFNα) were diarrhea (66% vs 21%), fatigue (62% vs 56%), nausea (58% vs 41%), anorexia (48% vs 42%), altered taste (47% vs 15%), mucositis/stomatitis (47% vs 5%), pain in extremity/limb discomfort (40% vs 30%), vomiting (39% vs 17%), bleeding, all sites (37% vs 10%), hypertension (34% vs 4%), dyspepsia (34% vs 4%), arthralgia (30% vs 19%), abdominal pain (30% vs 12%), rash (29% vs 11%), hand-foot syndrome (29% vs 1%), back pain (28% vs 14%), cough (27% vs 14%), asthenia (26% vs 22%), dyspnea (26% vs 20%), skin discoloration/yellow skin (25% vs 0%), peripheral edema (24% vs 5%), headache (23% vs 19%), constipation (23% vs 14%), dry skin (23% vs 7%), fever (22% vs 37%), and hair color changes (20% vs <1%). The most common grade 3/4 ARs (occurring in ≥5% of patients with RCC receiving SUTENT vs IFNα) were fatigue (15% vs 15%), hypertension (13% vs <1%), asthenia (11% vs 6%), diarrhea (10% vs <1%), hand-foot syndrome (8% vs 0%), dyspnea (6% vs 4%), nausea (6% vs 2%), back pain (5% vs 2%), pain in extremity/limb discomfort (5% vs 2%), vomiting (5% vs 1%), and abdominal pain (5% vs 1%).

Most common grade 3/4 lab abnormalities (advanced RCC): The most common grade 3/4 lab abnormalities (occurring in ≥5% of patients with RCC receiving SUTENT vs IFNα) included lymphocytes (18% vs 26%), lipase (18% vs 8%), neutrophils (17% vs 9%), uric acid (14% vs 8%), platelets (9% vs 1%), hemoglobin (8% vs 5%), sodium decreased (8% vs 4%), leukocytes (8% vs 2%), glucose increased (6% vs 6%), phosphorus (6% vs 6%), and amylase (6% vs 3%).

Most common ARs & most common grade 3/4 ARs (imatinib-resistant or -intolerant GIST): The most common ARs occurring in ≥20% of patients with GIST and more commonly with SUTENT than placebo (all grades, vs placebo) were diarrhea (40% vs 27%), anorexia (33% vs 29%), skin discoloration (30% vs 23%), mucositis/stomatitis (29% vs 18%), asthenia (22% vs 11%), altered taste (21% vs 12%), and constipation (20% vs 14%). The most common grade 3/4 ARs (occurring in ≥4% of patients with GIST receiving SUTENT vs placebo) were asthenia (5% vs 3%), hand-foot syndrome (4% vs 3%), diarrhea (4% vs 0%), and hypertension (4% vs 0%).

Most common grade 3/4 lab abnormalities (imatinib-resistant or -intolerant GIST): The most common grade 3/4 lab abnormalities (occurring in ≥5% of patients with GIST receiving SUTENT vs placebo) included lipase (10% vs 7%), neutrophils (10% vs 0%), amylase (5% vs 3%), and platelets (5% vs 0%).

Most common ARs & most common grade 3/4 ARs (advanced pNET): The most common ARs occurring in ≥20% of patients with advanced pNET and more commonly with SUTENT than placebo (all grades, vs placebo) were diarrhea (59% vs 39%), stomatitis/oral syndromes (48% vs 18%), nausea (45% vs 29%), abdominal pain (39% vs 34%), vomiting (34% vs 31%), asthenia (34% vs 27%), fatigue (33% vs 27%), hair color changes (29% vs 1%), hypertension (27% vs 5%), hand-foot syndrome (23% vs 2%), bleeding events (22% vs 10%), epistaxis (21% vs 5%), and dysgeusia (21% vs 5%). The most commonly reported grade 3/4 ARs (occurring in ≥5% of patients with advanced pNET receiving SUTENT vs placebo) were hypertension (10% vs 1%), hand-foot syndrome (6% vs 0%), stomatitis/oral syndromes (6% vs 0%), abdominal pain (5% vs 10%), fatigue (5% vs 9%), asthenia (5% vs 4%), and diarrhea (5% vs 2%).

Most common grade 3/4 lab abnormalities (advanced pNET): The most common grade 3/4 lab abnormalities (occurring in ≥5% of patients with advanced pNET receiving SUTENT vs placebo) included decreased neutrophils (16% vs 0%), increased glucose (12% vs 18%), increased alkaline phosphatase (10% vs 11%), decreased phosphorus (7% vs 5%), decreased lymphocytes (7% vs 4%), increased creatinine (5% vs 5%), increased lipase (5% vs 4%), increased AST (5% vs 3%), and decreased platelets (5% vs 0%).

Please see full Prescribing Information, including BOXED WARNING and Medication Guide, for SUTENT (sunitinib malate).