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8-K – Current report

On September 17, 2015 TG Therapeutics, Inc. (Nasdaq: TGTX) reported that it has reached an agreement with the U.S. Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design of a Phase 3 clinical trial for its proprietary combination of TG-1101 (ublituximab), its glycoengineered anti-CD20 monoclonal antibody, plus TGR-1202, the Company’s once-daily PI3K-delta inhibitor, for the treatment of Chronic Lymphocytic Leukemia (CLL) (Filing, 8-K, Manhattan Pharmaceuticals, SEP 17, 2015, View Source [SID:1234507484]). The SPA provides agreement that the Phase 3 trial design adequately addresses objectives that, if met, would support the regulatory submission for drug approval of both TG-1101 and TGR-1202 in combination.

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Full details of the Phase 3 clinical trial, called the UNITY-CLL trial, will be released at the launch of the study. The general study design is a randomized controlled clinical trial that includes two key objectives: first, to demonstrate contribution of each agent in the TG-1101 + TGR-1202 regimen (the combination sometimes referred to as "1303"), and second, to demonstrate superiority in Progression Free Survival (PFS) over the standard of care to support the submission for full approval of the combination. The study will randomize patients into four treatment arms: TG-1101 + TGR-1202, TG-1101 alone, TGR-1202 alone, and an active control arm of obinutuzumab + chlorambucil. An early interim analysis will assess contribution of each single agent in the TG-1101 + TGR-1202 combination regimen, which, if successful, will allow early termination of both single agent arms. A second interim analysis will be conducted following full enrollment into the study, which, if positive, the Company plans to utilize for accelerated approval. Assuming early termination of the TG-1101 and TGR-1202 single agent arms, the study will enroll approximately 450 patients.

Dr. John Gribben, Professor of Medicine and the Gordon Hamilton Fairley Chair of Medical Oncology at St. Bartholomew’s Hospital, Barts Cancer Institute in London, UK, will lead the UNITY-CLL Phase 3 as Study Chair. Dr. Gribben commented, "The recent introduction of novel targeted agents has already dramatically improved the standard of care for patients with relapsed or refractory CLL, and we have seen even greater activity when these agents are used in combination. Both ublituximab and TGR-1202 have demonstrated unique activity and tolerability as single agents, and in combination together. We are excited to lead this important and innovative trial, which has the potential to bring greater advances to patients in both the front-line and relapsed/refractory CLL setting."

Michael S. Weiss, Executive Chairman and Interim Chief Executive Officer of TG Therapeutics, stated, "Our number one goal has always been to accelerate the development of novel non-chemotherapy-based combination treatments for patients with B-cell malignancies. The UNITY-CLL study and the related SPA marks a major milestone for the Company and, if successful, could lead to a very broad label in the treatment of CLL, providing patients and physicians a new treatment option, and the Company a platform to build additional proprietary combinations in our continued effort to drive towards a cure. Our path to achieving this SPA, which we believe is the first for two novel investigational agents in the oncology division, was the result of a true collaboration with the FDA, for which we would like to recognize and thank the agency for its invaluable guidance throughout this process." Mr. Weiss continued, "Our clinical team has been hard at work preparing for the launch of this study, and we look forward to enrolling our first patients as soon as possible. Lastly, we are thrilled to have Dr. Gribben, a world-renowned authority in CLL, lead this important international study and share in his excitement in bringing our novel, non-chemotherapy combination regimen to patients in need."

Anti-Cancer Agent “Avastin®,” Application for Approval of Additional Indication of Recurrent/Advanced Cervical Cancer

On September 17, 2015 Chugai Pharmaceutical Co., Ltd. [Main Office: Chuo-ku, Tokyo. Chairman & CEO: Osamu Nagayama] (Chugai) (TOKYO: 4519) reported that it filed an application with the Japanese Ministry of Health, Labour and Welfare (MHLW) for the approval of an additional indication of recurrent/advanced cervical cancer for the anti-cancer agent/ anti-VEGF humanized monoclonal antibody, "AVASTIN I.V. Infusion 100mg/4mL and 400mg/16mL" [generic name: bevacizumab (recombinant) for Infusion] (Avastin) (Press release, Chugai, SEP 17, 2015, View Source [SID:1234507480]).

The application was filed based on overseas phase III studies (The GOG-0240 study) and Japanese phase II study (The JO29569 study) for the patients with cervical cancer.

The GOG-0240 study♯ evaluated the efficacy and safety profile of standard chemotherapies (paclitaxel and cisplatin or paclitaxel and topotecan) with or without Avastin in 452 patients with persistent, recurrent or metastatic cervical cancer.
The study met its primary endpoint of improving overall survival (OS) with a statistically significant 26 percent reduction in the risk of death, representing a median gain in survival of 3.9 months, compared with those who received chemotherapy alone [16.8 months vs. 12.9 months; HR=0.74, stratified log-rank test, p=0.0132].

The study showed that patients who received Avastin plus chemotherapy had a significantly improvement of progression free survilval (PFS) compared with those who received chemotherapy alone ［8.3 months vs. 6.0 months; HR=0.66, stratified log-rank test, p<0.0001］.

The study showed that patients who received Avastin plus chemotherapy had a significantly higher rate of tumor shrinkage (objective response rate, ORR) compared with those who received chemotherapy alone [45.4% (95% CI: 38.8-52.1%) vs. 33.8% (95% CI 27.6-40.4%); Chi-squared test, p=0.0117].

The safety profile in the study was consistent with previous reports of Avastin, except for an increase in gastrointestinal-vaginal fistulas observed in patients who received Avastin plus chemotherapy compared to those who received chemotherapy alone (8.3% vs. 0.9% respectively). All patients with gastrointestinal-vaginal fistulas had a history of prior pelvic radiation.

The JO29569 study evaluated the tolerability, safety and efficacy of Avastin plus paclitaxel and cisplatin. Within eight Japanese patients with advanced or recurrent cervical cancer enrolled in the study, seven patients were evaluated, and one patient was excluded before the start of the study. As a result, the tolerability of Avastin and chemotherapy was confirmed, and the harmful phenomenon to become the problem was not accepted, and no new safety finding were observed.

Avastin is approved for cervical cancer more than 40 countries worldwide including the US (August 2014) and EU (March 2015).

The number of patients newly diagnosed as cervical cancer in Japan continues to rise each year and is estimated to approximately 10,600 annual average in 2015-2019.*

As the top pharmaceutical company in the field of oncology in Japan, Chugai will work for the early approval to provide Avastin as a new treatment option for patients with recurrent/advanced cervical cancer and medical professionals.

♯ A 2 x 2 factorial design to compare four groups was employed in the GOG-0240 study. In addition to confirm the effectiveness of Avastin, the primary endpoints also included confirmation of effectiveness for chemotherapy without platinum agent (in combination with or without Avastin) against chemotherapy with platinum agent (in combination with or without Avastin).
* T. Sobue, et al., Cancer White Paper 2012, Shinoharashinsha Inc.

To Present CAR-T Phase I Clinical Trial Data for Non Small Cell Lung Cancer and Other Solid Tumors at 5th World Congress on Cancer Therapy

On September 16, 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 would give an oral presentation to discuss Phase I clinical trial data for EGFR (HER-1)-targeted Chimeric Antigen Receptor-Modified T-Cells (CAR-T) Immunotherapy for patients with Non-Small Cell Lung Cancer (NSCLC) and other solid tumors at the 5th World Congress on Cancer Therapy on September 28, 2015 (Press release, Cellular Biomedicine Group, SEP 16, 2015, View Source [SID:1234507486]).

Conference: 5th World Congress on Cancer Therapy, September 28-30, 2015 Atlanta, Georgia, USA

Title: EGFR (HER-1)-targeted Chimeric Antigen Receptor-Modified T-Cells Immunotherapy for Patients with Advanced or Relapsed/Refractory Solid Tumors
Oral Presentation: Scientific Program, September 28, 2015 18:05-18:25

Location: Hilton Atlanta Airport

Presenter: Wei Dong Han, MD, PhD, Chinese PLA General Hospital

The presentation expands on the data that will be presented at the European Cancer Congress poster presentation in Vienna on September 26, and will detail PLAGH/CBMG’s Phase I clinical trial data using Chimeric Antigen Receptor-Modified T-Cells (CAR-T) targeting EGFR (HER-1) for the treatment of patients with EGFR (HER-1) expressing advanced relapsed/refractory Non-Small Cell Lung Cancer (NSCLC) as well as other EGFR (HER-1) expressing solid tumors. The CAR-T trial was designed and conducted by Chinese PLA General Hospital ("PLAGH", Beijing, also known as "301 Hospital"), led by Principal Investigator Wei Dong Han, MD, PhD, head of PLAGH’s cancer immunotherapy department. Dr. Han and his research team have authored several CAR-T publications, including "Tolerance and Efficacy of Autologous or Donor-derived T-Cells Expressing CD19 Chimeric Antigen Receptors in Adult B-ALL with Extramedullary Leukemia" and "Effective Response and Delayed Toxicities of Refractory Advanced Diffused Large B-cell Lymphoma Treated by CD20-directed Chimeric Antigen Receptor-modified T-cells". (OncoImmunology (Impact Factor: 6.28). 03/2015; DOI: 10.1080/2162402X.2015.1027469 and Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002) The Company previously announced positive clinical data from its Phase I clinical trials using CAR-T constructs against CD19, CD20 and CD30 for late-stage blood cancers.

Company management will attend the conference and be available for discussions. Full detail of the presented data will be available on the Company website following the presentation.

OncoMed Presents Immuno-Oncology Data for GITRL-Fc Candidate at the Inaugural International Cancer Immunotherapy Conference

On September 16, 2015 OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported preclinical data for the company’s proprietary, wholly owned GITRL-Fc agent during the afternoon poster session of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) (Press release, OncoMed, SEP 16, 2015, View Source [SID:1234507482]).

GITRL is a member of the tumor necrosis factor (TNF) family of ligands and functions to activate the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptors) to enhance T-cell modulated immune responses. OncoMed’s GITRL-Fc agent is engineered using a novel single-gene linkerless GITRL trimer which enables effective GITR activation and robust anti-tumor immune response.

"The single-gene linkerless trimer technology we have created provides a flexible platform for the design of additional immuno-oncology agents, including bispecific agents," said Austin Gurney, PhD, Senior Vice President of Molecular and Cellular Biology. "We observed improved activation of GITR and highly potent single-agent activity using our GITRL fusion protein, and also noted that GITRL-Fc shows strong additivity with other immune checkpoint blockers. These data demonstrate a powerful new class of immunotherapeutic agent."

In a series of preclinical studies presented today, OncoMed’s GITRL-Fc agent activated GITR signaling more effectively than an agonist GITR antibody and promoted robust anti-tumor immune responses, including the potentiation of antigen-specific T-cell Th1 type immunity and a reduction of regulatory T-cell (Treg) immune suppressive activity. In multiple murine tumor graft models GITRL-Fc enabled complete eradication of some tumors as a single agent. The combination of GITRL-Fc with anti-PD1 or anti-PDL1 checkpoint inhibitors demonstrated enhanced anti-tumor activity compared to either agent alone.

"We are pleased to have presented research highlighting one of our proprietary immuno-oncology therapeutic agents," said John Lewicki, Chief Scientific Officer of OncoMed. "OncoMed is actively advancing GITRL-Fc with a goal of filing an Investigational New Drug (IND) application in 2016. This program further demonstrates our commitment to the ongoing discovery of innovative and next-generation anti-cancer therapies."

Fumiko Axelrod, Senior Scientist II, of OncoMed presented these data in a poster titled "GITRL-Fc, an immunotherapeutic agent that stimulates T-cell-mediated anti-tumor immune response" (Abstract number A058) during Poster Session A.

First half of 2015: landmark agreement with AstraZeneca and strong financial position

On September 17, 2015 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported its consolidated financial results for the first half of 2015 (Press release, Innate Pharma, SEP 16, 2015, View Source [SID:1234507481]).

Hervé Brailly, Chief Executive Officer of Innate Pharma, commented: "This first half of 2015 marked a major milestone in Innate Pharma’s corporate development with the signature of a landmark co-development and commercialization agreement in April with AstraZeneca to broaden and accelerate the development of IPH2201.

This agreement is a major step towards our corporate goal of further maturing the Company and developing capabilities in late stage development and potential commercial stage by keeping some co-development and co-promotion rights.

In the second half of 2015, additional Phase II clinical trials for IPH2201 will be opened and IPH4102 will start a multi-centric Phase I trial, becoming our third first-in-class, clinical-stage asset. With our increased financial flexibility, we are intensifying our efforts in R&D to enrich our pipeline of first-in-class proprietary antibodies.

As important new clinical data on lirilumab is generated, Innate Pharma is on track to leverage its unique positioning in the very promising area of immuno-oncology."