On July 6, 2015 Provectus Biopharmaceuticals reported that data from its phase 1 study of PV-10 for chemoablation of hepatocellular carcinoma (HCC) and cancer metastatic to the liver was presented on July 3, 2015 at the 6th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2015) in Osaka, Japan (Press release, Provectus Pharmaceuticals, JUL 6, 2015, http://www.pvct.com/pressrelease.html?article=20150706.1 [SID:1234506169]).

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The presenter was Dr. Sanjiv Agarwala, chief of medical oncology and hematology at St. Luke’s Cancer Center in Bethlehem, Pennsylvania, and professor of medicine at Temple University School of Medicine in Philadelphia, Pennsylvania. He serves as a principal investigator of the phase 1 clinical trial that produced the data presented, and is the lead investigator for the phase 3 clinical trial of PV-10 as an investigational treatment for melanoma which recently began. The poster presentation was titled "Phase 1 Study of PV-10 for Chemoablation of Hepatocellular Cancer and Cancer Metastatic to the Liver."

Based on the data presented, the researchers concluded that preliminary efficacy in treatment of liver tumors with PV-10, a 10% solution of rose Bengal, was observed with acceptable tolerability. The study is continuing at three study centers with two expansion cohorts to further assess safety and response in HCC and other cancers metastatic to the liver.

Provectus previously reported data on clinical and nonclinical testing of intralesional PV-10 as an investigational treatment for metastatic melanoma, where it has demonstrated high rates of complete response and durable local control in injected melanoma lesions. The phase 1 study reported at APPLE 2015 was designed to assess safety, pharmacokinetics and preliminary efficacy of PV-10 in subjects with non-resectable HCC or cancer metastatic to the liver.

In the phase 1 study, subjects having a target lesion in the liver at least 1 cm in diameter were administered a single percutaneous intralesional injection of PV-10 into their target lesion. Plasma concentrations of PV-10 from 1 hour to 28 days after injection were measured. Radiologic assessments of the injected target lesion were performed to determine response over an initial 28-day and longer term 9-15 month follow-up interval. Serum levels of potential liver injury markers were measured, and adverse events recorded.

In the initial study cohort, six subjects received PV-10 injections in two successive escalating dose cohorts of 0.25 and 0.50 mL per cm3 lesion volume. Significant adverse events were limited to injection site and photosensitivity reactions that resolved without sequelae. All injected tumors were stable in size at 28 days, and among four of the initial six tumors that had longer-term assessment, two had partial response.

The poster is now available online at: http://www.pvct.com/publications/APPLE-2015-PV-10-LC-01.pdf.

On July 7, 2015 Innate Pharma reported that the co-development and commercialization agreement with AstraZeneca on Innate Pharma’s proprietary anti-NKG2A antibody, IPH2201 (see announcement press release as of April, 24, 2015), received HSR clearance (Press release, Innate Pharma, JUL 6, 2015, View Source [SID:1234506176]). The companies will now begin to work together to accelerate and broaden the development of IPH2201, including in combination with MEDI4736, an anti-PD-L1 immune checkpoint inhibitor developed by MedImmune.

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On June 30, 2015, Innate Pharma received the initial payment of $250 million from AstraZeneca.

On July 6, 2015 Array BioPharma reported Array BioPharma’s wholly-owned RAF inhibitor, encorafenib, was showcased this past weekend at the 2015 ESMO (Free ESMO Whitepaper) World Congress of Gastrointestinal Cancer during an oral presentation (Press release, Array BioPharma, JUL 6, 2015, View Source;p=RssLanding&cat=news&id=2064825 [SID:1234506165]).

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At the meeting, data were shared from a Phase 1b trial and preliminary data from a 100-patient randomized Phase 2 expansion of that trial testing the combination of encorafenib and cetuximab, an EGFR inhibitor, with or without the addition of alpelisib (BYL719) 1, an investigational PI3K inhibitor in patients with BRAF-mutant colorectal cancer (BRAFmut CRC). Results from the study indicate that these combinations can be administered with good tolerability and show promising clinical activity in this patient population with high unmet medical needs. Patient enrollment is now complete in the Phase 2 study.

The preliminary Phase 2 results show an objective response rate (complete or partial response) and disease control rate (complete or partial response or stable disease) of 29% and 81%, respectively, for patients receiving the combination of encorafenib and cetuximab (encorafenib doublet), and 35% and 79%, respectively, for patients receiving the combination of encorafenib, cetuximab and alpelisib (encorafenib triplet).

Across both the encorafenib doublet and triplet treatment groups, most treatment related adverse events were grade 1 or 2 with few grade 3 or 4 adverse events. The most frequent treatment related adverse events across all grades for the encorafenib doublet were fatigue (36%), nausea (31%), lipase increased (24%), diarrhea (21%) and decreased appetite (21%), while for the encorafenib triplet they were diarrhea (39%), nausea (37%), fatigue (33%) and hyperglycemia (31%).

These results are consistent with the Phase 1b portion of the trial and are encouraging when compared to currently available therapies for BRAFmut CRC patients, as well as with other recently published investigational approaches in this population. Historically, response rates are very low for either single-agent EGFR or RAF inhibitor therapy in patients with BRAFmut CRC, which suggests a synergistic effect for the combination of encorafenib and cetuximab in this population.

"The combination of encorafenib and cetuximab demonstrated promising activity in this hard-to-treat subset of colorectal cancer patients," said Josep Tabernero, M.D., Head of the Medical Oncology Department at the Vall d’Hebron University Hospital and the Director of the Vall d’Hebron Institute of Oncology. "It is critical to identify new, effective treatments for BRAF mutant colorectal cancer patients, and I look forward to rapid development of this combination in a subsequent clinical trial."

1 alpelisib (BYL719) is an investigational Novartis Pharmaceuticals compound.

About Colorectal Cancer
Colorectal cancer is the third most common cancer among men and women in the United States, with approximately 132,000 new cases and nearly 50,000 deaths from the disease projected in 2015. BRAF mutations occur in approximately 10% percent of patients with colorectal cancer and predict for a poor response to standard therapies and an overall poorer prognosis relative to patients without these mutations.

About RAF and encorafenib
RAF is a key protein kinase in the MAPK signaling pathway that regulates several key cellular activities including proliferation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, such as melanoma, colorectal, lung and thyroid cancers. Encorafenib is a selective, small molecule, oral inhibitor which targets the RAF enzyme in this pathway. It is currently being developed in eleven active clinical trials, including the COLUMBUS trial, a Phase 3 study of encorafenib and binimetinib (MEK inhibitor) for patients with BRAF mutant melanoma. Array expects updated BRAF melanoma data from the Phase 2 combination trial (LOGIC-2) of binimetinib, encorafenib and a third agent (LEE011, BKM120, BFJ398 or INC280) will be submitted to a scientific conference later this year.

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On July 6, 2015 Celsion reported positive interim data from its ongoing open-label Phase 2 DIGNITY Trial of ThermoDox in recurrent chest wall (RCW) breast cancer (Press release, Celsion, JUL 6, 2015, View Source [SID:1234506166]). The trial is designed to enroll up to 20 patients at several U.S. clinical sites and is evaluating ThermoDox in combination with mild hyperthermia. Of the 17 patients enrolled and treated, 13 were eligible for evaluation of efficacy. Based on data available to date, every patient experienced a clinical benefit of their highly refractory disease within the ThermoDox treatment field, with a local response rate of 69% observed in the 13 evaluable patients, notably five complete responses (CR), four partial responses (PR) and four patients with stable disease (SD). The Company will complete enrollment in the study in the third quarter of 2015.

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"We have observed durable local responses in two-thirds of the patients treated using ThermoDox in three clinical trials to-date, which is significant considering the fact that these patients present with highly resistant chest wall tumors that had progressed on multiple previous therapies, including chemotherapy, radiation and hormone therapy," noted Dr. Nicholas Borys, Celsion’s senior vice president and chief medical officer. "We are aggressively pursuing opportunities to expand this program into Europe through the EURO-DIGNITY trial in which we expect to treat our first patient very soon."

These data are consistent with previously published Phase 1 data for ThermoDox plus hyperthermia in RCW breast cancer. The two similarly designed Phase 1 studies enrolled patients with highly resistant tumors found on the chest wall and who had progressed on previous therapies. Of the 29 patients treated in the two trials, 23 were eligible for evaluation of efficacy. A local response rate of 61% was reported in 14 of the 23 evaluable patients, with five complete responses and nine partial responses. A Clinical Response Rate (CR+PR+SD) was observed in 87% of the evaluable patients.

"These extremely impressive data position us to successfully pursue and take advantage of promising opportunities to accelerate the development and commercialization of ThermoDox in RCW breast cancer patients as we turn our attention to Europe and the initiation of EURO-DIGNITY, a multi-center study designed to evaluate ThermoDox’s potential to locally control chest wall lesions in earlier stage patients," stated Michael H. Tardugno, Celsion’s chairman, president and CEO. "Together, through our partnership with myTomorrows and our Early Access Program, our goal is faster commercialization and near-term revenue benefitting patients who are in dire need of more rapid access to new and better options for the treatment of this aggressive form of breast cancer."

The EURO-DIGNITY trial will evaluate ThermoDox plus hyperthermia and radiation in earlier stage breast cancer patients and is designed to support a registration filing in Europe. This study will be conducted in five countries with the support of key European investigators and with assistance from MedLogics Corporation, a hyperthermia device company based in Italy. In addition, Celsion has a license and distribution agreement with myTomorrows to implement an Early Access Program (EAP) for ThermoDox in all countries of the European Union plus Switzerland for the treatment of patients with RCW breast cancer. The Company expects to have ThermoDox available in mid-2015 for sale at commercial prices to physicians who are treating patients with limited therapeutic options. The EAP provides physicians with access to products in later stage development that demonstrate evidence of clinical benefit with an acceptable safety profile and a quality manufacturing process in place.

On July 2, 2015 Provectus Biopharmaceuticals reported that data from its phase 1 study of PV-10 for chemoablation of hepatocellular carcinoma (HCC) and cancer metastatic to the liver was presented at the ESMO (Free ESMO Whitepaper) 17th World Congress on Gastrointestinal Cancer (ESMO-GI) (Press release, Provectus Pharmaceuticals, JUL 2, 2015, http://www.pvct.com/pressrelease.html?article=20150702.1 [SID:1234506021]). The main conclusion was that preliminary evidence of efficacy in treatment of liver cancers with PV-10 was observed. The poster presentation was made by Eric Wachter, Ph.D., Chief Technology Officer of Provectus.

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Provectus has previously reported data on clinical and nonclinical testing of intralesional PV-10, a 10% solution of rose bengal, as an investigational treatment for metastatic melanoma, where it has demonstrated high rates of complete response and durable local control in melanoma lesions. The current phase 1 study reported at ESMO (Free ESMO Whitepaper)-GI was designed to assess safety, pharmacokinetics, and preliminary efficacy of PV-10 in subjects with non-resectable HCC or other types of cancer metastatic to the liver.

In the phase 1 liver study, subjects having a target lesion in the liver at least 1 cm in diameter were administered a single percutaneous injection of PV-10 into their target lesion. Plasma concentrations of PV-10 from 1 hour to 28 days after injection were measured. Radiologic assessments of the injected target lesion were performed to determine response over an initial 28-day and longer term 9-15 month follow-up period. Serum levels of potential liver injury markers were measured, and adverse events recorded.

In the initial study cohort, six subjects received PV-10 injections in two successive escalating dose cohorts of 0.25 and 0.50 mL per cm3 lesion volume. Significant adverse events were limited to injection site and photosensitivity reactions that resolved without sequelae. All injected tumors were stable in size at 28 days, and among four of the initial six tumors that had longer-term assessment, two had partial response.

Based on these data, the researchers concluded that preliminary efficacy in treatment of liver tumors with PV-10 was observed with acceptable tolerability. The study is continuing at three study centers with two expansion cohorts to further assess safety and response in HCC and other cancers metastatic to the liver.

The poster is now available online at: http://www.pvct.com/publications/ESMO-2015-PV-10-LC-01.pdf.

About ESMO (Free ESMO Whitepaper) 17th World Congress on Gastrointestinal Cancer

The ESMO (Free ESMO Whitepaper) 17th World Congress on Gastrointestinal Cancer is the premier global event in the field, encompassing malignancies affecting every component of the gastrointestinal tract and aspects related to the care of patients with gastrointestinal cancer, including screening, diagnosis and the latest management options for common and uncommon tumors. For additional information about the ESMO (Free ESMO Whitepaper) 17th World Congress, please visit View Source