On November 20, 2017 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported that an abstract with partial results from the monotherapy portion of BL-8040’s Phase 2a COMBAT study in pancreatic cancer was accepted for presentation at the ASCO (Free ASCO Whitepaper) 2018 Gastrointestinal Cancers Symposium, to take place January 18-20, 2018 in San Francisco, CA (Press release, BioLineRx, NOV 20, 2017, View Source;p=RssLanding&cat=news&id=2317838 [SID1234522148]).

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The Phase 2a study, named the COMBAT study, is an open-label, multicenter, single-arm trial designed to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., (known as MSD outside the United States and Canada), in up to 30 subjects with metastatic pancreatic adenocarcinoma. The study is primarily designed to evaluate the clinical response, safety and tolerability of the combination of these therapies. In addition, the study will evaluate multiple pharmacodynamic parameters, including the ability to improve infiltration of T cells into the tumor and their reactivity, for both BL-8040 as a monotherapy, as well as for the combination of BL-8040 and KEYTRUDA. The study is being conducted in the US, Israel and additional territories.

"We are very pleased that the abstract presenting our partial monotherapy results for the COMBAT study were accepted to this important clinical conference. Because of the embargo policy of the conference, we won’t be able to share the data by the end of the year, but rather disclose it in January 2018, when the abstracts are released," commented Philip Serlin, Chief Executive Officer of BioLineRx. "As for today, we can report that enrollment of the study has been completed and we are meeting our timelines for conclusion of the study and topline results by the second half of 2018. We are excited about the upcoming topline results in 2018, and continue to fully support our development plan in combination with immune checkpoint inhibitors".

In September 2016, BioLineRx announced the initiation of the COMBAT study, its first Phase 2a study for evaluating the clinical efficacy of BL-8040 in combination with KEYTRUDA, for the treatment of patients with metastatic pancreatic cancer who relapse to previous therapies. The COMBAT study is being conducted by BioLineRx under a collaboration agreement between BioLineRx and MSD, through a subsidiary, to support a Phase 2a study investigating BioLineRx’s BL-8040 in combination with KEYTRUDA in patients with metastatic pancreatic cancer.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells and to be effective at inducing direct tumor cell death. Additional findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with KEYTRUDA, which blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect tumor cells survival, BL-8040 has the potential to enable activated larger amount of T cells to better reach tumor cells in the fight against pancreatic cancer.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells and immune-cells from the bone marrow, thereby sensitizing cancer cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis) and mobilizing immune-cells. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On November 20, 2017 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that new preclinical data for its novel covalent EGFR inhibitor were presented at the Society for Neuro-Oncology 22nd Annual Meeting, November 16-19, in San Francisco (Press release, Trillium Therapeutics, NOV 20, 2017, View Source [SID1234522151]).

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Poster Presentation: TTI-2341: A novel, orally bioavailable, brain-penetrant, covalent epidermal growth factor receptor (EGFR) inhibitor for treatment of glioblastoma multiforme (GBM) and brain metastases of non-small cell lung cancer (NSCLC).

This poster presentation highlighted preclinical data for TTI-2341, a novel covalent EGFR inhibitor. TTI-2341 had potent activity against a broad range of EGFR variants, including disease-relevant mutants T790M and C797S. TTI-2341 was shown to penetrate the blood brain barrier and demonstrated superior ADME properties and oral bioavailability relative to benchmark drugs afatinib and osimertinib. Notably, TTI-2341 achieved greater than 20-fold higher free drug brain exposure compared to osimertinib and was well tolerated at levels expected to be efficacious.

"Aberrant EGFR activity is clearly implicated in CNS tumors, particularly glioblastoma multiforme and brain metastases of non-small cell lung cancer," said Trillium CEO Dr. Niclas Stiernholm. "Currently available EGFR inhibitors have demonstrated limited efficacy due to poor penetration of the blood brain barrier and low activity against resistance-associated EGFR mutations. Our emerging preclinical data suggests that TTI-2341 can overcome these limitations."

PVS-RIPO, more commonly referred to as the re-engineered poliovirus, is the Sabin type 1 polio vaccine, genetically modified so it cannot harm or kill normal cells (Company Web Page, Istari Oncology, NOV 19, 2017, View Source [SID1234522139]).
We believe there are several important advantages of PVS-RIPO as an immunotherapy for cancer treatment:
The poliovirus receptor CD155 is expressed in virtually all solid cancers, as well as dendritic cells, macrophages and other immune cells.
PVS-RIPO infects and kills tumor cells that express CD155.
PVS-RIPO infection of immune cells facilitates induction of an antitumor immune response.
PVS-RIPO is the only oncolytic virus that is not destroyed by the Type 1 interferon response caused by these viruses.
Other oncolytic viruses kill or limit dendritic cells. PVS-RIPO stimulates dendritic cell activity and immune function.
Cancer patients who are immune to polio and have been boosted with the Salk vaccine experience a recall immune response upon intratumoral PVS-RIPO infusion.
For targeting glioblastoma, the vaccine is delivered by direct intratumoral delivery via convection-enhanced delivery (CED), which by-passes the blood-brain barrier and reduces systemic toxicity. CED is commonly used, and we believe it is reproducible in multiple centers. Less than 5% of the tumor volume needs to be injected to achieve high drug concentrations throughout the tumor. BrainLAB and Therataxis software allow highly accurate and reproducible drug distribution and injection accuracy.
The FDA granted PVS-RIPO Breakthrough Therapy Designation on May 10, 2016. Breakthrough Therapy Designation conveys all fast track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior FDA managers, and eligibility for rolling review and priority review.
The FDA also granted PVS-RIPO Orphan Drug designation for glioblastoma on May 26, 2016. Benefits of this designation include tax credits of 50% of the clinical drug testing cost awarded upon approval, waiver of NDA/BLA application fee, and seven years of data exclusivity upon approval (that is, it bars the FDA from approving any other application for the same drug for the same orphan disease or condition for seven years).

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On November 20, 2017 Samsung Bioepis Co., Ltd. reported the European Commission’s (EC) marketing authorization of ONTRUZANT, a biosimilar referencing Herceptin (trastuzumab), for the treatment of early breast cancer, metastatic breast cancer and metastatic gastric cancer (Press release, Samsung Bioepis, NOV 20, 2017, View Source [SID1234522145]). ONTRUZANT is the first trastuzumab biosimilar to receive regulatory approval in Europe.

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The EC approval of ONTRUZANT applies to all 28 European Union (EU) member states and the European Economic Area (EEA) member states of Norway, Iceland and Liechtenstein. ONTRUZANT will be commercialized by MSD, which is known as Merck in the United States and Canada.

"Breast cancer remains the most common form of cancer affecting women. We hope ONTRUZANT will play an important role expanding patient access to trastuzumab across the region," said Christopher Hansung Ko, President & CEO of Samsung Bioepis. "Through relentless process innovation and an uncompromising commitment to quality, we remain dedicated to advancing one of the industry’s strongest biosimilar pipelines, so that more cancer patients and healthcare systems across Europe will benefit from biosimilars."

ONTRUZANT is the fourth biosimilar developed by Samsung Bioepis to receive EC marketing authorization. Samsung Bioepis has also received marketing authorizations for Benepali (etanercept), Flixabi (infliximab) and Imraldi (adalimumab).

On November 20, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMpower150 study met its co-primary endpoint of progression-free survival (PFS) and demonstrated that the combination of TECENTRIQ (atezolizumab) and Avastin (bevacizumab) plus chemotherapy (paclitaxel and carboplatin) provided a statistically significant and clinically meaningful reduction in the risk of disease worsening or death (PFS) compared to Avastin plus chemotherapy in the first-line treatment of people with advanced non-squamous non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, NOV 20, 2017, View Source [SID1234522149]). Initial observations for the co-primary endpoint of overall survival (OS) are encouraging. These data are not fully mature and the next OS analysis is expected in the first half of 2018. Safety for the TECENTRIQ and Avastin plus chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

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These data will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno Oncology Congress in Geneva, Switzerland in December 2017.

"We are extremely encouraged by these results and will submit these data to health authorities globally with the goal of bringing a potential new standard of care for the initial treatment of lung cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "In addition to first-line NSCLC, we are testing the ability of TECENTRIQ and Avastin to enhance the potential of the immune system to combat a broad range of other cancers."
About the IMpower150 study

IMpower150 is a multicentre, open-label, randomised, controlled Phase III study evaluating the efficacy and safety of TECENTRIQ in combination with chemotherapy (carboplatin and paclitaxel) with or without Avastin in people with stage IV non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease. It enrolled 1,202 people of which those with ALK* and EGFR mutations were excluded from the primary ITT analysis. People were randomised (1:1:1) to receive:

TECENTRIQ plus carboplatin and paclitaxel (Arm A), or
TECENTRIQ and Avastin plus carboplatin and paclitaxel (Arm B), or
Avastin plus carboplatin and paclitaxel (Arm C, control arm).

During the treatment-induction phase, people in Arm A received TECENTRIQ administered intravenously at 1200 mg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. Following the induction phase, people received maintenance treatment with TECENTRIQ (1200 mg every 3 weeks) until loss of clinical benefit or disease progression.

People in Arm B received induction treatment with TECENTRIQ (1200 mg) and Avastin administered intravenously at 15 mg/kg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. People then received maintenance treatment with the TECENTRIQ Avastin regimen until disease progression (Avastin) or loss of clinical benefit/disease progression (TECENTRIQ).

People in Arm C received induction treatment with Avastin administered intravenously at 15 mg/kg plus intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. This was followed by maintenance treatment with Avastin alone until disease progression.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1), and OS. This analysis of the IMpower150 PFS endpoint was only statistically powered to demonstrate a comparison between Arm B versus Arm C.

The primary analysis of the co-primary PFS endpoint in IMpower150 was assessed in two populations: all randomised people without an ALK or EGFR genetic mutation (intention-to-treat wild-type**) and in a subgroup of people who had a specific biomarker (T-effector "Teff" gene signature expression). IMpower150 met its PFS co-primary endpoint per study protocol for both populations assessed.

About NSCLC
Despite recent advances in the treatment of NSCLC, there is still a need for new treatment options. Lung cancer is the leading cause of cancer death globally.1 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.2 Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.2

About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.
Currently, Roche has eight Phase III lung cancer studies underway, evaluating TECENTRIQ alone or in combination with other medicines.

TECENTRIQ is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Avastin (bevacizumab)
Avastin is a biologic cancer treatment approved in combination with chemotherapy for the first-line treatment of advanced NSCLC and, to-date, has helped over 500,000 patients lead longer lives. Avastin is considered a standard of care for the first-line treatment of advanced NSCLC and has been proven to significantly extend overall survival (OS). Avastin is currently approved in combination with any platinum-based chemotherapy in Europe, and with paclitaxel/carboplatin in the US, in first-line non-squamous NSCLC, based on results of the pivotal Phase III E4599 study. Avastin was the first medicine to help people with previously untreated advanced, non-squamous NSCLC live longer (OS) than one year when added to chemotherapy.
About the TECENTRIQ (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support the use of TECENTRIQ plus Avastin in combination. The TECENTRIQ and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers, including first-line advanced NSCLC. Avastin, in addition to its established anti-angiogenic effects, may further enhance TECENTRIQ’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.
About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.
By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with TECENTRIQ to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.