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Sumitomo Dainippon Pharma Announces Clinical Data of Investigational Cancer Stemness Inhibitor Napabucasin were presented at 2017 ASCO GI Symposium

On January 23, 2017 Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka, Japan; President: Masayo Tada; "Sumitomo Dainippon Pharma") reported that two poster presentations of napabucasin (BBI608) were delivered on January 21, 2017 (U.S. time) at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, January 19 to 21, 2017, in San Francisco (Press release, Dainippon Sumitomo Pharma, JAN 22, 2017, View Source [SID1234517525]).

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Overview of poster presentations at the ASCO (Free ASCO Whitepaper)-GI

1. Results of Phase 1b/2 study of napabucasin with FOLFIRI, or FOLFIRI and bevacizumab administered to colorectal cancer patients. (BBI608-246:NCT02024607)

Abstract Number 593

Title Cancer stemness inhibition and chemosensitization: Phase Ib/II study of cancer stemness inhibitor napabucasin (BBI608) with FOLFIRI +/- bevacizumab (Bev) administered to colorectal cancer (CRC) patients (pts)

Lead presenter Johanna Bendell, Sarah Cannon Cancer Research Institute/Tennessee Oncology, Nashville, TN

Overview of the study result 63 CRC pts with an average of >2 prior therapy lines were enrolled. This phase Ib/II study suggests napabucasin may sensitize chemorefractory CRC to FOLFIRI +/- Bev and encouraging signs of synergistic activity was observed in CRC pts regardless of p-STAT3 status.

Safety No pharmacokinetic interactions or dose-limiting toxicity was observed. Most common adverse events (AEs) included grade 1/2 diarrhea, nausea, vomiting and fatigue. 1 pt had grade 4 diarrhea and 27 pts had grade 3 AEs, including diarrhea (14), fatigue (4), dehydration (2), electrolyte imbalance (4), nausea (1), vomiting (1), abdominal pain (1) and weight loss (1), all of which resolved with dose reduction and supportive care. Efficacy Among 56 pts enrolled who received RECIST evaluation, disease control rate(DCR:CR+PR+SD) was observed in 88%(49 pts) with an overall response rate(ORR:CR+PR) of 29%(16 pts) with 1 pt achieving CR. 2 (Reference: DCR and ORR) Subset DCR ORR Evaluable ITT Evaluable ITT FOLFIRI naïve 93% (28/30) 82% (28/34) 33% (10/30) 29% (10/34) FOLFIRI exposed 81% (21/26) 72% (21/29) 23% (6/26) 21% (6/29) p-STAT3high 84% (26/31) 79% (26/33) 26% (8/31) 24% (8/33) p-STAT3low 92% (23/25) 77% (23/30) 32% (8/25) 27% (8/30)

2. Results of Phase 1b/2 study of napabucasin with panitumumab administered to K-ras wild-type patients with metastatic colorectal cancer (BBI608-224: NCT01776307)

Abstract Number 677

Title BBI608-224: A phase Ib/II study of cancer stemness inhibitor napabucasin (BBI608) administered with panitumumab in K-ras wild-type patients with metastatic colorectal cancer.

Lead presenter Tim Larson, Minnesota Oncology, Minneapolis, MN

Overview of the study result 72 pts were enrolled, 48 pts were evaluable by RECIST of which 7 (15%) and 41 (85%) had 2 or ≥3 prior treatment lines, respectively. Of the 48 evaluable pts, 37 (77%) were previously treated with an anti-EGFR agent. Napabucasin was safely combined with panitumumab at full dose with no unexpected adverse events and no evidence of pharmacological interaction. Encouraging anti-tumor activity in pts with K-ras, wt mCRC was observed. Napabucasin may sensitize pts to repeat anti-EGFR therapy.

Safety The safety profile was consistent with that of each agent as monotherapy and most common AEs included grade 1/2 diarrhea, nausea, abdominal cramps, and vomiting.

Efficacy Among 48 pts enrolled who received RECIST evaluation, Disease Control Rate (DCR) was observed in 54.2%(26 pts) of which 2 pts achieved PR (4%) and 24 pts achieved SD (50%). Among 37 pts previously treated with anti-EGFR therapy, DCR was observed in 54%(20 pts) compared with DCR of 54.5% observed in 6 out of 11 anti-EGFR naïve pts receiving a scan.

(Reference: mPFS and mOS)

Population Subgroup mPFS (months) mOS (months) ITT Anti-EGFRNaïve n=18 3 13.3 Anti-EGFRExposed n=54 2.1 9.1 Total n=72 2.1 9.1 3 Evaluable Anti-EGFRNaïve n=11 3.9 17.9 Anti-EGFRExposed n=37 2.6 9.9 Total n=48 3 12.2 (Reference)

About napabucasin (BBI608)
Napabucasin is an investigational first-in-class anti-cancer agent created and currently under development by Boston Biomedical, Inc. Napabucasin is an orally-administered small molecule agent designed to inhibit cancer stemness pathways by targeting STAT3

Pipeline Review Check

CureMeta is a Therapeutic Biotech Company Developing Novel Antibody-Drug-Conjugates to Unique Embryonic Cancer Stem Cell Targets (Company Pipeline, CureMeta, JAN 22, 2017, View Source [SID1234517499]).

PAMREVLUMAB PANCREATIC CANCER CLINICAL DATA PRESENTED AT ASCO 2017 GASTROINTESTINAL CANCERS SYMPOSIUM

On January 20, 2017 FibroGen, Inc. (Nasdaq:FGEN) reported that updated results from an ongoing clinical study of pamrevlumab (FG-3019) in combination with standard-of-care chemotherapy in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC) were presented in a poster session during the ASCO (Free ASCO Whitepaper) 2017 Gastrointestinal Cancers Symposium in San Francisco (Press release, FibroGen, JAN 20, 2017, View Source;p=IROL-news&nyo=0 [SID1234517531]). Pamrevlumab is a fully human monoclonal therapeutic antibody that inhibits connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders.

"I am very encouraged by these additional results from this clinical trial of pamrevlumab evaluated in combination with standard-of-care chemotherapy in patients with locally advanced pancreatic ductal adenocarcinoma," said Vincent J. Picozzi, Jr., M.D., Director of the Pancreas Center, Virginia Mason Hospital & Seattle Medical Center, and principal investigator. "Based on our participation in this trial, and a previous clinical study (FGCL- MC3019-028), I believe pamrevlumab has the potential to provide meaningful benefit for pancreatic cancer patients with locally advanced and/or metastatic disease."

Of the 33 subjects enrolled to date:

Twenty-two have been randomized to pamrevlumab plus chemotherapy, 10 remain on treatment
– Three discontinued treatment due to complications not related to pamrevlumab, and nine completed treatment
– Seven subjects who completed treatment met protocol defined criteria eligible for tumor resection and were considered operable following treatment. Three subjects had complete tumor removal (R0), and one subject had microscopic tumor remaining after surgery (R1)
Of the 11 subjects randomized to chemotherapy alone, five subjects discontinued treatment due to various reasons, and six subjects completed treatment
– Of the six subjects who received chemotherapy alone, one subject met protocol defined criteria eligible for tumor resection and had a complete tumor removal (R0)
Differences in overall survival (OS) between subjects treated with and without pamrevlumab look encouraging
There were no complications from laparoscopy or biopsies that were clinically significant or delayed dosing, and, to date, there have been no safety imbalances between treatment arms.
In this open-label, randomized study, pamrevlumab in combination with gemcitabine and nab-paclitaxel is compared to chemotherapy alone for the treatment of patients with locally advanced pancreatic ductal adenocarcinoma who have failed resection scoring and were characterized as inoperable assessed by histology, CT scans, and laparoscopy. Subjects are randomized to six cycles of chemotherapy with gemcitabine and nab-paclitaxel, with or without pamrevlumab. The study has enrolled 33 patients, and is targeted to enroll up to 42 subjects.

About Pancreatic Ductal Adenocarcinoma and Connective Tissue Growth Factor

Pancreatic ductal adenocarcinoma (PDAC), or pancreatic cancer, is the fourth leading cause of cancer deaths in the United States. According to the National Cancer Institute, in 2016, there were approximately 53,000 new cases of pancreatic cancer projected in the United States alone. Pancreatic cancer is aggressive and typically not diagnosed until it is largely incurable. Most patients are diagnosed after the age of 45, and overall five-year survival is about 7%, due to many factors, including advanced stage at diagnosis and limited response to currently available therapies (View Source). PDAC tumors often exhibit a high degree of desmoplasia, characterized by extensive connective tissue stroma and elevated levels of Connective Tissue Growth Factor (CTGF). Cancer-stroma interactions affect tumorigenesis, angiogenesis, resistance to therapy and metastatic spread of tumor cells. CTGF is overexpressed in PDAC and facilitates local desmoplasia, tumor progression and metastasis in animal models.

About Pamrevlumab

Pamrevlumab (FG-3019) is an investigational therapeutic antibody developed by FibroGen to inhibit the activity of CTGF, a common factor in chronic fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. FibroGen is currently conducting clinical studies of pamrevlumab in idiopathic pulmonary fibrosis, pancreatic cancer, and Duchenne muscular dystrophy.

In desmoplastic, or fibrotic, cancers such as pancreatic cancer, CTGF in the extensive fibrous stroma associated with the tumor promotes abnormal proliferation of stromal cells and tumor cells. Studies in a transgenic mouse model of pancreatic cancer indicate that treatment with pamrevlumab in combination with chemotherapy may enhance the efficacy of chemotherapy and improve survival.

Regorafenib from Bayer Granted Priority Review in Japan for the Second-Line Treatment of Liver Cancer

On January 20, 2017 Bayer reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted priority review to Bayer Yakuhin, Ltd., Osaka, Japan, for regorafenib in the second-line treatment of patients with unresectable hepatocellular carcinoma (HCC) (Press release, , JAN 20, 2017, View Source;sessionID=1485224246 [SID1234517530]). Regorafenib was submitted for marketing approval in HCC in Japan in October 2016. The MHLW grants priority review to medicines on the basis of their clinical usefulness and severity of the disease. Regorafenib is already approved under the brand name Stivarga in many countries, including Japan, to treat metastatic colorectal cancer and unresectable and/or metastatic gastrointestinal stromal tumors.

"Liver cancer is one of the leading cancer-related causes of death in Japan. Nexavar as the first and only approved systemic treatment for HCC has been a major advance in this field, but effective second-line treatment options are urgently needed for patients", said Dr. Joerg Moeller, member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Head of Development. "We welcome the priority review for regorafenib in Japan as it supports our efforts to make the compound available as early as possible in the second-line setting for HCC in Japan."

The regulatory submission for regorafenib is based on data from the international, multicenter, placebo-controlled Phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma] trial. The trial investigated regorafenib in patients with unresectable hepatocellular carcinoma (HCC) whose disease had progressed during treatment with sorafenib (Nexavar) tablets. Results showed that regorafenib significantly improved overall survival (OS) compared to placebo (HR 0.63; 95% CI 0.50-0.79; p<0.001), which over the trial period represents a 37 percent reduction in the risk of death for patients who received regorafenib plus best supportive care (BSC) compared to patients treated with placebo plus BSC. The median OS was 10.6 months in patients treated with regorafenib, compared to 7.8 months in patients who received placebo plus BSC. The safety and tolerability was generally consistent with the known profile of regorafenib, with no clinically meaningful differences in health-related quality of life (HRQoL) between the regorafenib and placebo plus BSC groups. Data from the study were first presented at the 18th World Congress on Gastrointestinal Cancer (WCGC) in June 2016 and published online on December 5, 2016 in the peer-reviewed journal The Lancet.

Regorafenib has also been submitted to the regulatory authorities in the US and EU for the treatment of second-line HCC.

About the RESORCE trial
The Phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma] clinical trial enrolled 573 patients whose disease had progressed during treatment with sorafenib. Patients were randomized in a 2:1 ratio to receive either regorafenib or placebo plus best supportive care.

Patients received 160 mg regorafenib once daily or placebo, for 3 weeks on/1week off, with 28 days constituting one full treatment cycle. The primary endpoint of the study was overall survival, and secondary endpoints were time to progression, progression-free survival, objective tumor response rate and disease control rate. Health-related quality of life was assessed by the FACT-Hep and EQ-5D questionnaires. Safety and tolerability were also continuously monitored.

About Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and represents approximately 70-85 percent of liver cancer worldwide. Liver cancer is the sixth most common cancer in the world and the second leading cause of cancer-related deaths globally. More than 780,000 cases of liver cancer are diagnosed worldwide each year (52,000 in the European Union, 501,000 in the Western Pacific region and 30,000 in the United States) and the incidence rate is increasing. In 2012, approximately 746,000 people died of liver cancer including approximately 48,000 in the European Union, 477,000 in the Western Pacific region and 24,000 in the United States.

About Regorafenib (Stivarga)
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

Regorafenib is approved under the brand name Stivarga in more than 90 countries worldwide, including the U.S., countries of the EU and Japan for the treatment of metastatic colorectal cancer (mCRC). The product is also approved in over 80 countries, including the U.S., countries of the EU and Japan, for the treatment of metastatic gastrointestinal stromal tumors (GIST). In the EU, Stivarga is indicated for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy, as well as for the treatment of adult patients with unresectable or metastatic GIST who progressed on or are intolerant to prior treatment with imatinib and sunitinib.

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.

MATEON THERAPEUTICS TO PRESENT DATA ON STUDY OX4218 IN NEUROENDOCRINE TUMORS AT ASCO GASTROINTESTINAL CANCERS SYMPOSIUM

On January. 20, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported the presentation of final data from Study OX4218 in patients with neuroendocrine tumors (NETs) at a poster session at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium being held today in San Francisco.

Study OX4218 was a multi-center, open label, phase 2 clinical trial to investigate the safety and activity of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low-to-intermediate-grade unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors/carcinoid (PNETs or GI-NETs) with elevated biomarkers. Following patients’ completion of Study OX4218, patients were eligible to enroll in Study OX4219, a long term extension study, if they achieved a biomarker or symptom response. In OX4218 patients were treated with CA4P 60 mg/m2 on Days 1, 8, and 15 of a 21-day cycle for 3 cycles, and in OX4219 patients received CA4P maintenance on Day 1 of a 21-day cycle until disease progression or up to one year.

A total of 18 patients were enrolled in OX4218. One patient (6%) experienced significant symptomatic improvement as measured by ECOG Status and had a partial response per investigator-assessed RECIST and an additional 7 patients (39%) had stable disease. In addition, a majority of patients (53%) experienced an improvement in patient-reported quality of life. A statistically significant mean change in biomarkers from baseline, the primary endpoint of the study, was not achieved in OX4218 due to the small sample size along with a high intra- and inter-patient variability observed in the biomarkers. A total of 7 patients were enrolled in OX4219, of which 5 patients (71%) had stable disease, including one that continued for 14 months. The partial response and stable disease analyses, as well as other measures from the trial, suggest that CA4P monotherapy has activity in this indication.

"The results of OX4218 and OX4219 confirm that CA4P monotherapy has efficacy in the indications studied, as we have seen with the investigational drug in a number of other monotherapy trials," said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "However, we believe that the efficacy of CA4P only becomes compelling when it is used in combination with an anti-angiogenic agent, due to the complementary mechanisms of action for the two agents. Based on the evidence of efficacy observed in this trial, plus an understanding of the benefits of combination therapy, a lead investigator in this trial is sponsoring a 20 patient study in NETs using CA4P in combination with everolimus (AFINITOR, marketed by Novartis), an anti-angiogenic agent which is already approved and commonly used in this indication."

Overall CA4P monotherapy was well tolerated. Treatment related adverse events were reported in 77% of subjects. The most common Grade 3-5 AEs ( > 10%) included: anemia, abdominal pain, fatigue, hypertension, and ALT and AST increases. One Grade 5 adverse event, carcinoid syndrome, was reported and attributed to the underlying disease.