On July 31, 2017 Kite Pharma, Inc. (Nasdaq:KITE), a leading cell therapy company, reported that it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for axicabtagene ciloleucel as a treatment for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) who are ineligible for autologous stem cell transplant (Press release, Kite Pharma, JUL 31, 2017, View Source [SID1234519941]). This application represents the first chimeric antigen receptor (CAR) T-cell therapy submitted to the EMA. Axicabtagene ciloleucel is currently under review by the U.S. Food and Drug Administration (FDA), and the FDA has set a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2017.

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The MAA for axicabtagene ciloleucel is supported by data from the ZUMA-1 trial, which met the primary endpoint of objective response rate (ORR), with 82 percent (p < 0.0001) of patients achieving a response after a single infusion of axicabtagene ciloleucel. At a median follow-up of 8.7 months, 44 percent of patients were in ongoing response, which included 39 percent of patients in complete response (CR). The most common Grade 3 or higher adverse events included cytokine release syndrome and neurologic events, which were generally reversible.

"The MAA submission of axicabtagene ciloleucel marks an important global milestone in the development of engineered T cell therapy," said Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer of Kite. "We are excited to work closely with the EMA, Committee for Medicinal Products for Human Use (CHMP) and Committee for Advanced Therapies (CAT) to help bring this potentially transformative therapy to patients in the EU."

Non-Hodgkin lymphoma (NHL) is a type of blood cancer that affects around 93,000 people in Europe every year.i DLBCL is one of the subtypes of NHL that is aggressive or fast growing.ii While many patients can achieve and maintain complete remission after initial treatment, patients who experience relapse or do not respond to initial treatment historically have poor outcomes. The company estimates that approximately 7,800 patients in the EU 5 alone may benefit from CAR-T therapy.

In May 2016, the CHMP and CAT granted access to its newly established Priority Medicines (PRIME) regulatory initiative for axicabtagene ciloleucel in the treatment of patients with refractory DLBCL. Access to the PRIME initiative is granted by the EMA to support the development and accelerate the review of new therapies to treat patients with a high unmet need.

About axicabtagene ciloleucel

Kite’s lead product candidate, axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

On July 31, 2017 Diffusion Pharmaceuticals, Inc. (NASDAQ:DFFN), a clinical stage biotechnology company developing novel small molecule therapeutics for cancer and other hypoxia-related diseases, reported that it has selected a premier Clinical Research Organization (CRO) to conduct a Phase 3 clinical trial of Diffusion’s lead molecule, trans sodium crocetinate (TSC), in inoperable glioblastoma multiforme (GBM) patients (Press release, Diffusion Pharmaceuticals, JUL 31, 2017, View Source [SID1234519940]). Diffusion also entered into agreements with top tier partners to manage the MRI imaging, clinical data management, drug supply and other functions related to the trial. Diffusion plans to initiate this Phase 3 clinical trial by the end of 2017.

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"After reaching the critical milestone of manufacturing drug product for our Phase 3 trial earlier this month, we have now reached another major milestone with the selection of our full clinical trial team, including a leading global CRO and first-in-class providers of imaging and data management services," said David Kalergis, Diffusion’s Chairman and CEO. "We are pleased to have engaged such skilled and experienced partners for this important endeavor."

Diffusion is now interacting with the FDA on details regarding the design and execution of the planned Phase 3 study. The study will focus on treating newly diagnosed GBM patients who have been judged by their medical team to be inoperable, usually because of the size or location of the tumor. Due to their poor prognosis, these patients are often excluded from participation in other GBM clinical trials. In the Company’s Phase 2 GBM trial, the TSC-treated inoperable group showed a nearly four-fold increase in survival at two years, compared to the control.

On July 31, 2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported the signing of a joint research agreement with the National Cancer Center Japan regarding the "MASTER KEY Project," an industry-academia joint project led by the National Cancer Center Japan (Press release, Chugai, JUL 31, 2017, View Source [SID1234519939]). Chugai will collaborate with the National Cancer Center Japan to promote drugs research and development on rare cancers and genomic medicines.

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Rare cancers are defined as cancers with a prevalence of fewer than six cases out of a population of 100,000 persons per year*. As there are an extremely small number of patients and there are more issues related to diagnosis and therapies compared to other types of cancers, there is no consolidated clinical data making it difficult to conduct research, development and clinical studies on these types of cancers.
* View Source (Japanese only)

This project was started in May 2017 with the aim of integrating the advanced know-how, research support functions of the National Cancer Center Japan, and the seeds and development strategies of pharmaceutical companies to build a joint foundation for industry-academia to comprehensively and efficiently promote the development of therapies for rare cancers.

As a top pharmaceutical company in the oncology area, Chugai has participated in Japan’s first industry-academia collaborative nationwide cancer genome screening project, "SCRUM-Japan." Chugai believes that the participation in the "MASTER KEY Project" will further strengthen its collaboration with academia, serving as a first step towards resolving the difficult issues related to rare cancers.

Through participation in the "MASTER KEY Project", Chugai strives to conduct research and development on innovative drugs for rare cancers with limited treatment options and high unmet medical needs.

About the MASTER KEY Project
The MASTER KEY Project (Marker Assisted Selective ThErapy in Rare cancers: Knowledge database Establishing registrY Project) is an industry-academia joint project to promote research and development on rare cancers and genomic medicine led by the National Cancer Center Japan. 11 pharmaceutical companies are participating in the project. The project will conduct registry research to establish a large-scale database that will serve as basic data for research by collecting genomic information, clinical information, and prognosis data on patients with rare cancers. It will also conduct basket trials, a new clinical study method, promoting investigator-initiated or company sponsored clinical trial using drugs suitable for the biomarkers of patient populations with specific biomarkers without restricting or specifying cancer types. The registry clinical research commenced in May 2017.

On July 31, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and Clovis Oncology, Inc. (Nasdaq:CLVS) reported the companies have entered into a clinical collaboration agreement to evaluate the combination of Bristol-Myers Squibb’s immunotherapy Opdivo and Clovis Oncology’s poly (ADP-ribose) polymerase (PARP) inhibitor Rubraca in pivotal phase 3 clinical trials in:

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Advanced ovarian cancer: First-line maintenance treatment study to evaluate Rubraca + Opdivo, Rubraca, Opdivo and placebo in newly diagnosed patients with stage III/IV high-grade ovarian, fallopian tube, or primary peritoneal cancer who have completed platinum-based chemotherapy (Press release, Bristol-Myers Squibb, JUL 31, 2017, View Source [SID1234519938]).
Advanced triple-negative breast cancers (TNBC): First-line maintenance treatment study to evaluate Rubraca + Opdivo, Rubraca, Opdivo and chemotherapy in patients with stage IV or recurrent locally advanced inoperable TNBC associated with a homologous recombination deficiency (HRD).
The collaboration will also include a Phase 2 study to evaluate the safety and efficacy of Opdivo in combination with Rubraca in patients with metastatic castration-resistant prostate cancer (mCRPC). The Opdivo + Rubraca combination in mCRPC will be conducted as an arm of a larger Bristol-Myers Squibb-sponsored study.

Rubraca is an oral, small molecule inhibitor of PARP enzymes, including PARP-1, PARP-2, and PARP-3, being developed for the treatment of solid tumors associated with homologous recombination deficiency (HRD), defined as the presence of a deleterious BRCA1 or BRCA2 mutation, a deleterious mutation in another gene involved in DNA damage repair, and/or a high percentage of tumor genome with LOH, a phenotypic consequence of HRD. Opdivo is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells and other immune cells. The overlap in immuno-biology linked to these agents supports the potential for synergy of PARP inhibition and PD-1 blockade. Preclinical evidence has demonstrated that PARP inhibition can trigger inflammation, cell death and increase T-cell infiltration within tumors.

"We are very enthusiastic about studying Rubraca and Opdivo in combination, and the potential to create new treatment options for patients with multiple tumor types, as well as for patients beyond those with BRCA mutations," said Patrick J. Mahaffy, President, and CEO of Clovis Oncology. "This substantial clinical collaboration in ovarian, triple-negative breast and prostate cancers represents a significant effort by Clovis and Bristol-Myers Squibb to realize that potential."

"This clinical collaboration addresses areas of unmet medical need where the combination of Opdivo and Rubraca may lead to an additional treatment option for patients with difficult to treat cancers," said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. "We are committed to investigating a wide range of oncology therapies and look forward to studying the combination of Clovis’ PARP inhibitor and our immunotherapy."

The planned multi-arm clinical trials will be conducted in the U.S., Europe, and possibly additional countries. Clovis will be the study sponsor and conducting party for the ovarian cancer study and Bristol-Myers Squibb will be the study sponsor and conducting party for the breast and prostate cancer studies. Specific terms of the agreement were not disclosed. All three studies are expected to begin before the end of 2017.

About Ovarian Cancer

According to the World Cancer Research Fund International, ovarian cancer is the seventh most common cancer in women worldwide (18th most common cancer overall), with 239,000 new cases diagnosed in 2012. There are often no specific initial symptoms, and in an estimated 80 to 85% of ovarian cancer cases, the cancer has spread to other parts of the body before a person is diagnosed and can be treated. Ovarian cancer ranks fifth in cancer deaths in the U.S. and causes more deaths than any other cancer of the female reproductive system.

About Triple-Negative Breast Cancer

Breast cancer is the most frequently diagnosed cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012, accounting for 25% of all new cancer cases in women according to the International Agency for the Research of Cancer (IARC) of the World Health Organization. More than one out of every 10 breast cancers are found to be triple-negative, meaning the cancer does not have the biomarkers that predict response to hormonal therapy or therapies that target HER2 receptors. Triple negative tumors are often aggressive and have a poorer prognosis compared to hormone receptor-positive breast cancers.

About Castration-Resistant Prostate Cancer

Prostate cancer is the second most frequently diagnosed cancer in men, with 1.1 million new cases diagnosed worldwide in 2012. Unlike many early-stage prostate cancers that need normal levels of testosterone to grow, castration-resistant prostate cancer (CRPC) continues to grow even when the amount of testosterone in the body is reduced to castrate levels. CRPC patients have a very high likelihood of having or developing metastases, meaning the cancer has spread to other areas of the body. While the 5-year survival rate for most stages of prostate cancer is almost 100%; the 5-year survival rate for prostate cancer that has spread to distant lymph nodes, bones, or other organs is approximately 29%.

On July 31, 2017 AstraZeneca and MedImmune, its global biologics research and development arm, reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for Imfinzi (durvalumab) for the treatment of patients with locally-advanced, unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemoradiation therapy (Press release, AstraZeneca, JUL 31, 2017, View Source [SID1234519937]).

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "For patients who have not progressed following chemoradiation therapy the only current option is active monitoring. Unfortunately, for the majority of patients, their cancer will progress to metastatic disease, typically within 12 months. Imfinzi is the first immuno-oncology medicine to show a clinically-significant benefit in this earlier, non-metastatic setting, so following the Breakthrough Designation we hope to bring it to patients as soon as possible."

The Breakthrough Therapy Designation is designed to expedite the development and regulatory review of new medicines that are intended to treat a serious condition and that have shown encouraging early clinical results, which demonstrate substantial improvement on a clinically-significant endpoint over available medicines and when there is significant unmet medical need.

The Breakthrough Therapy Designation for Imfinzi was granted on the basis of interim results from the Phase III PACIFIC trial, a randomised, double-blinded, placebo-controlled multi-centre trial of Imfinzi as sequential treatment in patients with locally-advanced, unresectable (Stage III) NSCLC who had not progressed following standard platinum-based chemotherapy concurrent with radiation therapy. This achievement follows the recent accelerated approval from the US FDA for Imfinzi in previously-treated patients with advanced bladder cancer, and is the fourth Breakthrough Therapy Designation AstraZeneca has received from the FDA for a New Oncology cancer medicine over the past three years, the second for Imfinzi.

Data from the PACIFIC trial have been submitted for presentation at a forthcoming medical meeting.

Imfinzi is also being tested in the adjuvant NSCLC setting in the ADJUVANT Phase III trial. In the Stage IV 1st-line setting for patients with advanced NSCLC, Imfinzi as monotherapy and in combination with tremelimumab, an anti-CTLA4, is being tested in the MYSTIC, NEPTUNE, and PEARL Phase III trials. The POSEIDON trial is evaluating Imfinzi with and without tremelimumab in combination with chemotherapy.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled multi-centre trial of Imfinzi as sequential treatment in unselected patients with locally-advanced, unresectable (Stage III) NSCLC who have not progressed following platinum-based chemotherapy concurrent with radiation therapy.

The trial is being conducted in 235 centres across 26 countries, including the US, Canada, Europe, South and Central America, Japan, Korea, Taiwan, South Africa and Australia. The primary endpoints of the trial are PFS and OS, and secondary endpoints include landmark PFS and OS, objective response rate and duration of response.

About Imfinzi

Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response.

Imfinzi continues to be studied in multiple monotherapy trials and combination trials with tremelimumab and other potential new medicines in immuno-oncology. Imfinzi is being assessed in Phase III trials as a monotherapy in various stages of NSCLC, in small-cell lung cancer (SCLC), in metastatic urothelial cancer (mUC) and in head and neck squamous cell carcinoma (HNSCC). The combination of Imfinzi and tremelimumab is being assessed in Phase III trials in NSCLC, SCLC, mUC and HNSCC and in Phase I/II trials in hepatocellular carcinoma (HCC) and haematological malignancies.

About Locally-Advanced (Stage III) NSCLC

Stage III lung cancer is divided into two stages (IIIA and IIIB), which are defined by how much the cancer has spread locally and the possibility of surgery. This differentiates it from Stage IV disease, when the cancer has metastasised to other organs.

Stage III lung cancer represents approximately one third of NSCLC incidence and was estimated to affect around 100,000 patients in the G7 countries in 2016. About half of these patients have tumours that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.