On September 29, 2015 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, http://www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or the "Company"), reported that the Journal of Clinical and Cellular Immunology has published a paper titled, "The Potential of Intralesional Rose Bengal to Stimulate T-Cell Mediated Anti-Tumor Responses (Filing, 8-K, Provectus Pharmaceuticals, SEP 29, 2015, View Source [SID:1234507601])." The paper can be found online at View Source

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Authors Ajay V Maker, Bellur Prabhakar, and Krunal Pardiwala state that their "article serves to evaluate the potential of intralesional rose bengal [RB] to stimulate T-cell mediated anti-tumor responses in in-vitro, pre-clinical, and clinical studies." The review covers findings in both animal models and human clinical trials covering the use of intralesional RB in the treatment of: melanoma, breast cancer, ovarian cancer, gastric cancer and sarcoma.

They conclude, "Our current research is establishing the role of RB in generating anti-tumor immune responses in gastrointestinal cancer and liver metastases. Decrease in tumor burden and stimulation of an immune response with PV-10 has been demonstrated in animal models of metastasis, and correlations of these responses in clinical studies is consistent with such results. That PV-10 treatment can potentially increase circulating cytotoxic T-cells, even in patients who were previously treated with immune-activating checkpoint blockade, supports the possibility that RB induced cytotoxicity may activate T-cells that are responsible for the bystander effect on untreated lesions. As such, intralesional therapy with RB may be a promising new mode of therapy to stimulate T-cell mediated anti-tumor immune responses."

On September 28, 2015 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a biomedicine firm engaged in the development of effective stem cell therapies for degenerative diseases and immunotherapies for cancer, reported that it responded to inquiries from investors and the scientific community about its Immuno-Oncology cell therapy platform as it relates to information surrounding CD19, CD20 and CD30 (Press release, Cellular Biomedicine Group, SEP 28, 2015, View Source [SID:1234507605]).

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Dr. William (Wei) Cao, Chief Executive Officer of Cellular Biomedicine Group commented, "We are taking a proactive approach to addressing inquiries from the investment and scientific community on the Company’s Immuno-Oncology cell therapy platform on a more real-time basis. This area has been well followed and we would like to take this opportunity to expand on frequently asked questions and dispel misinformation in the marketplace. We will continue to keep our stakeholders apprised of ongoing business and pipeline developments."

Can CBMG clarify what constructs were a part of the acquisition from PLA General Hospital’s ("PLAGH") Chimeric Antigen Receptor T cell (CAR-T) therapy and was CART-33 a part of this acquisition?
As the Company had previously announced on February 9, 2015, the recombinant expression vectors CD-19, CD-20, CD-30 and Human Epidermal Growth Factor Receptor’s (EGFR or HER1) were the only constructs acquired in addition to its respective patent applications and Phase I clinical data. At no time has CBMG acquired CART-33, which is a classification of which the Company is unaware. Details related to the acquisition and the respective constructs can be found in the Company’s Form 8-Ks filed February 9, 2015, March 25, 2015, May 26, 2015; the Form 10-K filed March 31, 2015; and the Form 10-Qs filed on May 15 and August 13, 2015. Any statement made otherwise is simply false.

In order for the community to better benchmark CBMG’s data relative to its competitors, can the Company clarify CBMG’s lead drug as it relates to patients enrolled with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL) and the respective indications of each construct?

Different from other clinical trials that have been published, CBMG’s lead drug candidate is CD-20 CART and not CD-19 CART for DLBCL. At this time we would like to reiterate that the clinical trial data presented for CD-19 CART was for B-cell Lineage Acute Lymphoblastic Leukemia (B-cell ALL); CD20 CART was for Advanced Diffuse Large B Cell Lymphoma (DLBCL) and CD30 CART was for Hodgkin’s lymphoma. It is important to note here that comparing clinical outcomes from two different drugs that target two different tumor antigens could be misleading if the detailed background of the trials are not provided. Clinical trial data for all three constructs can be found registered with the U.S. National Institute of Health (NIH) at the following links: NCT01864889, NCT01735604, NCT02259556.

What is the accurate overall response rate (ORR) for CD-19 CART?
As we had previously announced on March 25, 2015, nine adult patients with relapsed or chemotherapy-refractory B-cell lineage acute lymphoblastic leukemia (B-ALL) were enrolled in this CAR-CD19 T cell therapy trial. Different from other competitive trials, pediatric patients were not enrolled as part of this trial. Results showed a complete response (CR) rate of 22.2% (two out of nine patients) and a partial response (PR) rate of 44.4% (four out of nine patients) for an overall response rate (ORR) of 66.7% (six out of nine patients). Further subgroup analysis showed an overall response rate (ORR) of 71.4% (five out of seven patients) in the six CD-19 patients with extramedullary involvement and one patient with no extramedullary lesions and treated with autologous CAR-CD19 T cell therapy. In the six CD19 patients with extramedullary leukemia involvement or bulky adenopathy, an overall response rate (ORR) of 66.7% (four out of six patients) was achieved. It should be noted that 2 out of the 9 patients were infused with allogeneic CD-19 CART. When comparing clinical trial results that were carried out with autologous CART only, the patients infused with allogeneic CART should be excluded to allow meaningful comparison.

Can the Company clarify the overall response rate (ORR) for its CD-20 CART and CD-30 CART?
As the Company had previously reported on March 25, 2015, the results for CAR-CD20 T cell therapy trial showed an overall response rate (ORR) of 83% with five of six patients with evaluable clinical efficacy achieving complete response (CR) or partial response (PR). The Company had also previously reported on May 22, 2015, the results for CAR-CD30 T cell therapy trial showed overall response rate (ORR) of 71% with five of seven patients achieving CR or partial response PR.

Can the Company explain which vector was used in the genetic modification of patients’ T cells with anti-CD19 CAR and anti-CD20 CAR?
The transduction method utilized in the genetic modification of patients’ T cells is in fact the lentiviral vector transduction method. The Company made an error in the filing with clinicaltrials.gov and will rectify the situation immediately.

What is the next major clinical milestone for CBMG?
The Company will present CAR-T Phase I/II clinical trial data for Non Small Cell Lung Cancer (NSCLC) and Cholangiocarcinoma (CC or CCA) at the 5th World Congress on Cancer Therapy on September 28 in Atlanta, Georgia.

On September 28, 2015 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a biomedicine firm engaged in the development of effective stem cell therapies for degenerative diseases and immunotherapies for cancer, reported results from an expanded Phase I/II clinical trial evaluating the safety, feasibility and anti-tumor activity of its Chimeric Antigen Receptor-Modified T-Cells (CAR-T) immunotherapy (CBM-EGFR.1) targeting wild type EGFR (Epidermal Growth Factor Receptor) for the treatment of patients with EGFR expressing advanced relapsed/refractory solid tumors. Based on the results from 24 patients treated with CBM-EGFR (Press release, Cellular Biomedicine Group, SEP 28, 2015, View Source [SID:1234507606]).1 (17 patients with non-small cell lung cancer (NSCLC), 5 patients with cholangiocarcinoma, 1 patient with pancreatic cancer and 1 patient with renal cell carcinoma (RCC)), the early results showed that CBM-EGFR.1 immunotherapy was safe, well tolerated, and had positive signal of clinical activity in several indications. The data was selected for a late-breaking oral presentation entitled EGFR-Targeted Chimeric Antigen Receptor-Modified T Cells Immunotherapy for Patients With EGFR-Expressing Advanced or Relapsed/Refractory Solid Tumors at the 5th World Congress on Cancer Therapy in Atlanta, Georgia on September 28, 2015. The abstract can be viewed online here. The results from the first 11 NSCLC patients in the trial outlined in the abstract, entitled Chimeric Antigen Receptor-Modified T-Cells for the Immunotherapy of Patients with HER-1 Expressing Advanced Relapsed/Refractory Non-Small Cell Lung Cancer was presented at the 2015 European Cancer Congress’ (ECCO) annual meeting held in Vienna, Austria from September 25-29, 2015. The abstract can be viewed online here.

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About the Trial
The CBM-EGFR.1 phase I/II trial was designed and conducted by Chinese PLA General Hospital ("PLAGH", Beijing, also known as "301 Hospital"), led by Principal Investigator Wei Dong Han, M.D., Ph.D., head of the cancer immunotherapy department and director of molecular immunology department of the life science institute of PLAGH. The trial enrolled 24 EGFR positive (defined as at least 50% membrane staining of EGFR based on immunohistochemistry), advanced, relapsed/refractory patients with NSCLC, cholangiocarcinoma, RCC or pancreatic cancer. Most of the NSCLC patients failed EGFR-TKI therapy prior to CBM-EGFR.1 treatment. All patients provided written informed consent before enrollment, and received dose escalating infusions of CBM-EGFR.1 cells with or without conditioning chemotherapy. Autologous CBM-EGFR.1 cells were generated from 50 to 80 ml peripheral blood after a 10 to 12-day in vitro expansion, and the total CAR-expressing T cell number of 1×106/kg was set as an output control. The presence of EGFR positive cells in tumor tissues was evaluated by means of immunohistochemistry (IHC). Serum cytokines such as IL-6, IL-2, TNF-a, copy numbers of CAR-EGFR.1 transgene in peripheral blood and biopsied tissues, were monitored periodically according to assigned protocol. Clinical responses were evaluated using RECIST 1.1 and adverse events were graded by CTCAE 4.0. This study is registered with the U.S. National Institute of Health (NIH) here.

Highlight of Phase I/II clinical trial for CBMG CAR-T products in multiple advanced, refractory/relapsing solid tumors

First known report of positive safety and signal of clinical activity of EGFR CAR-T in multiple solid tumor indications
Most NSCLC patients treated with CBM-EGFR.1 failed EGFR-TKI therapy prior to CBM-EGFR.1 treatment
Overall disease control rate (DCR) is 79% (19 of 24). 100% DCR in cholangiocarcinoma (5/5), 71% DCR in NSCLC (12/17)
Objective response rate (ORR) of 25% in combined indications: 2 complete response (CR) and 1 partial response (PR) in cholangiocarcinoma, 2 PR in NSCLC and 1 PR in pancreatic cancer

The clinical responses were evaluated with RECIST1.1 and immune-related response criteria by a team of experts, and adverse events were graded with CTCAE 4.0. Of the 24 patients with evaluable clinical outcome, the overall DCR was 79% (19 of 24). Under standard protocol, an independent review of the clinical data by a separate team of experts will commence at the end of the trial. Of the 5 cholangiocarcinoma patients reported here, 2 achieved CR, 1 achieved PR, and 2 had stable disease (SD). The single pancreatic cancer patient had a PR and a single RCC patient achieved SD. Of the 17 NSCLC patients treated, 2 had PR, 10 had SD, and 5 had progressive disease. Of the 26 adverse events experienced by patients, only 1 was grade 3-4 where the patient experienced serum lipase increase. No patients experienced drug related deaths. Grade 1-2 pruritus was the most frequent adverse event experienced by patients (9/26; 35%). Desquamation and constipation are the other two frequently observed adverse events in the trial (4/26 each; 15%). Only 3 out of 24 patients exhibited Grade 2 cytokine release syndrome within one week post infusions. The median dose of transfused CBM-EGFR.1 cells was 1.18×107 cells/kg (IQR, 0.76 to 1.43×107 cells/kg). The transgene copies measured by PCR in both blood and biopsy tissues post CBM-EGFR.1 infusions indicated the trafficking of CART cells into the tumor tissues. Pathological eradication of EGFR positive tumor cells after CBM-EGFR.1 treatment was observed in tumor biopsies, along with clear evidence of the CBM-EGFR.1 cells detected in tumor-infiltrating T cells in all patients with available tumor biopsies post treatment.

Yihong Yao, Ph.D., Chief Scientific Officer of the Company commented, "The early signal of clinical activity, especially those observed in patients with late stage cholangiocarcinoma, and those with late stage NSCLC that failed prior EGFR-TKI therapy, are very encouraging. To our knowledge this is the first report of positive safety and tolerability data of EGFR CAR-T in multiple solid tumor indications. We are moving forward to confirm the safety and tolerability profile of CBM-EGFR.1 in cholangiocarcinoma and NSCLC, and will actively explore the opportunities in other solid tumor indications by implementing state-of-the-art translational medicine strategy in the clinical development. We are determined to look for early possibilities of conducting multi-center Phase IIb trials to validate the clinical activity from early observations. We have also begun to evaluate potential partners to develop an immunohistochemistry based diagnostic assay to aid in the patient selection whenever needed. We are optimistic that CBM-EGFR.1 will be able to provide late stage cancer patients with another option to extend their lives."

The Company also previously announced positive clinical data results for its Phase I clinical trials for CBM-CD19.1, CBM-CD20.1 and CBM-CD30.1 CAR-T assets targeting late-stage hematological cancer. Clinical trial data for all three constructs can be found registered with the U.S. National Institute of Health (NIH) here: NCT01864889, NCT01735604, NCT02259556.

"We are extremely excited by the recent developments resulting from the collaboration between CBMG and PLA General Hospital. These two reports on CBM-EGFR.1 therapy for late stage solid tumors have clearly demonstrated our ability to innovate, advance boundaries between basic research and translational medicine and streamline the manufacture of CAR-T and clinical treatment. We are confident and determined to be at the forefront of clinical development of these breakthrough CAR-T therapies for late stage cancer patients with solid tumors," concluded Dr. William (Wei) Cao, Chief Executive Officer of Cellular Biomedicine Group.

On September 28, 2015 Bristol-Myers Squibb reported that actor Jack Huston, a star of the hit television show Boardwalk Empire and the upcoming remake of Ben Hur, took on an important new role as lung cancer advocate as he challenged Europeans to A.C.T. – be Aware, get Checked, and Talk with their doctor about lung cancer. After losing his grandfather to lung disease and his best friend and mentor, Peter Blythe, to lung cancer, Huston was motivated to take action by partnering with Bristol-Myers Squibb Company (NYSE:BMY) and leading advocacy group Lung Cancer Europe (LuCE) to ask the public, particularly those at high risk, what’s their Next Lung Cancer A.C.T.?

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Lung cancer is the number one cancer killer in Europe with an estimated 353,000 deaths each year – more than breast cancer, colorectal and prostate cancers combined. In Europe, lung cancer is the third most common cancer among women. Despite the growing prevalence, a new survey conducted among more than 8,200 participants in nine European countries showed that lung cancer knowledge is very low, with nearly six in 10 people (57%) surveyed saying that they are not knowledgeable about the disease. Further, one in five people (20%) could not identify the symptoms of lung cancer, including persistent cough, and one in 10 people (10%) do not know the risk factors, such as exposure to cigarette smoking.

Huston, along with lung cancer advocates and oncologists, unveiled the survey results at the European Cancer Congress (ECC) 2015 in Vienna, as well as a short film highlighting the personal stories of lung cancer patients.

"Like many Europeans, I know firsthand the devastating impact cancer can have on a family," said Huston. "I’ve joined The Next Lung Cancer A.C.T. in hopes of encouraging others to be mindful of the risk factors and symptoms of lung cancer and the importance of taking action now."

Key findings of the survey showed:

Six in 10 respondents (62%) believe lung cancer is a smoker’s disease, although smoking is only one risk factor for lung cancer
45 percent believe that breast cancer is the leading cause of death among women as compared to 8 percent who responded lung cancer

Nearly half of all respondents (46%) said they are not concerned about getting lung cancer, including 43 percent who have experience with lung cancer and 36 percent who are daily smokers
Eight in 10 people (83%) have never spoken to their doctor about lung cancer; an equal number of smokers (77%) also report this behavior

Following the survey, the majority of respondents (90%) expressed a willingness to take action to reduce their risk of lung cancer, including reducing their exposure to carcinogen (cancer-causing substances or agents) (50%), limit exposure to secondhand smoke (48%), and talking to their doctor (43%)

"It’s a pivotal time for lung cancer – the disease remains an enormous public threat in Europe but we are seeing promising research in the lung cancer space," said LuCE board member and lung cancer survivor, Regine Deniel Ihlen. "That is why now is the time for people to act by being aware, taking steps to get checked and having an ongoing dialogue with their physicians."

"At ECCO we are committed to helping people understand the signs that indicate that they may have cancer, as well as recognizing ways in which the disease may be prevented," said Professor Martine Piccart, President of the European CanCer Organization (ECCO). "That is why we are happy to be hosting the launch of this campaign, and we wish it every success."

"At Bristol-Myers Squibb, we are committed to fighting lung cancer through our research in oncology and by supporting the global lung cancer community," said Emmanuel Blin, senior vice president, Head of Commercialization, Policy and Operations, Bristol-Myers Squibb. "The Next Lung Cancer A.C.T. represents our ongoing dedication to helping to empower those with cancer by providing them with knowledge to better understand the risks of lung cancer and how to take action."

About The Next Lung Cancer A.C.T.

The Next Lung Cancer A.C.T. is a public awareness campaign designed to encourage the public, particularly those at high risk of lung cancer, to take ACTion against the disease by being Aware, getting Checked and Talking to their doctor. The Next Lung Cancer A.C.T. is sponsored by Bristol-Myers Squibb, in collaboration with Lung Cancer Europe (LuCE). For more information on the campaign please visit www.TheNextLungCancerACT.eu.

About the Survey and TNS

TNS conducted the survey. TNS, the world’s largest custom research agency, is a well-recognized research group for their quality and authoritative research.

Participants in the 12-question, self-administered online omnibus survey were 8,263 Europeans, ages 16-54 across nine different countries in Europe: Austria, Denmark, Germany, Great Britain, Italy, Netherlands, Spain, Switzerland and Turkey. The survey was conducted between July 30, 2015 and August 7, 2015. The results were tested at 95% significant. At 95% confidence level, if the study were repeated, the results would not fluctuate more than 3.0-3.4 percentage points in either direction for the population surveyed in each country.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year, according to the World Health Organization (WHO). In Europe alone, lung cancer is responsible for an estimated 353,000 deaths from the disease every year – more than breast cancer, colorectal and prostate cancers combined. It has the highest economic burden of all cancers in the European Union, costing an estimated €18.8 billion or 15 percent of overall cancer costs.

On September 28, 2015 ArQule, Inc. (NASDAQ:ARQL) reported preliminary results for the ongoing phase 1b expansion study in oncology for ARQ 092, an orally available selective pan-AKT inhibitor (Press release, ArQule, SEP 28, 2015, View Source [SID:1234507584]). The results were presented at the 2015 ESMO (Free ESMO Whitepaper) European Cancer Congress on September 27th, 2015.

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Thus far 25 patients have been treated in the study, and four partial responses (PRs) have been observed. These include two patients with the AKT1 E17K mutation and one patient with the PIK3CA H1047R mutation. Mutation status for a fourth patient could not be determined. Of the four PRs, two were observed in follicular lymphoma, one in breast cancer and one in endometrial cancer. The poster presentation can be accessed in the "Investor and Media" section of our website, www.arqule.com, under "Recent Data Presentations."

The phase 1b study follows completion of the phase 1a dose escalation portion of the trial that enrolled 82 patients and tested various dosages and dose regimens. In the phase 1a trial after one PR was observed in a patient with chronic lymphocytic lymphoma, the study was expanded to phase 1b with a focus on lymphoma, endometrial cancer and tumors harboring AKT (AKT1 E17K) or PI3K (PIK3CA H1047R) mutations.

"The preliminary results of the phase 1b expansion cohort are very encouraging," said Dr. Brian Schwartz, Head of Research and Development and Chief Medical Officer at ArQule. "The observation of four PRs in the 25 patients we have enrolled thus far validate our strategy to focus the trial on specific cancers with the AKT and PI3K mutations. We will continue to explore ARQ 092 in both cancer and rare diseases harboring these mutations."

ArQule continues to enroll patients in the phase 1b study while assessing next steps for ARQ 092 in oncology. In parallel, ArQule collaborators at the National Institute of Health (NIH) received approval of the Investigational New Drug (IND) application to begin a phase 1 trial with ARQ 092 in Proteus syndrome, a rare disease that is caused by a mutation of the AKT1 gene.

About ARQ 092 and the AKT Pathway

ARQ 092 is an orally available, selective small molecule inhibitor of the AKT kinase. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.

ARQ 092, the lead compound in ArQule’s AKT program, has completed Phase 1a clinical testing and has advanced into Phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphoma and tumors harboring either AKT or PI3K mutations. A number of next-generation compounds in the Company’s AKT program are in early to late stages of pre-clinical development.