On October 19, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE:BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported top-line results from the dual combination arm of the Phase 2a COMBAT/KEYNOTE-202 study, evaluating patients with metastatic pancreatic adenocarcinoma (PDAC) treated with BL-8040 in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside of the United States and Canada) (Press release, BioLineRx, OCT 19, 2018, View Source;p=irol-newsArticle&ID=2372469 [SID1234529979]). The results show encouraging disease control and extended overall survival, particularly in patients undergoing second-line treatment. The data, entitled, "A Phase 2a Trial to Assess the Safety and Efficacy of BL-8040 and Pembrolizumab in Patients with Metastatic Pancreatic Adenocarcinoma (PDAC)," will be presented on October 20, 2018 at 5:15 pm CET at the immuno-oncology poster discussion session co-chaired by the principal investigator of the study at the European Society for Medical Oncology 2018 Congress, which is being held October 19-23, in Munich, Germany.

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The study included 37 patients with metastatic PDAC who had disease progression after one or more previous lines of treatment. Study treatment consisted of an initial 5-day priming period of BL-8040 monotherapy, followed by repeated 3-week cycles of BL-8040 in combination with KEYTRUDA. In addition to clinical efficacy assessments, the study included a number of pharmacodynamic assessments to support BL-8040’s mechanism of action as an immuno-oncology agent.

The data show that the treatment regimen was safe and well tolerated. The disease control rate (patients exhibiting a response or stable disease) was 34.5% for the evaluable population (N=29), including 1 patient (3.4%) with a partial response showing a 40% reduction in tumor burden, as well as 9 patients (31%) with stable disease, with a median treatment time of 72 days (37-267). Median overall survival (OS) in all patients (N=37) was 3.3 months with a 6-month survival rate of 34.4%. A significant observation was made in the subpopulation of patients receiving the study drugs as a second-line treatment (N=17), where the median overall survival was 7.5 months, with a 6-month survival rate of 51.5%. This compares favorably with historical median overall survival data of 6.1 months for the only currently approved second-line PDAC treatment (a chemotherapy combination of Onivyde, 5-FU and leucovorin).

The clinical activity correlates with previously announced partial pharmacodynamic results from the BL-8040 monotherapy period of this study, in which BL-8040 induced infiltration of T-cells into the core and periphery of metastatic lesions. Additional in-depth analyses of biopsies taken at screening and following monotherapy or combination treatment of BL-8040 and KEYTRUDA have now been completed and will be presented at the poster discussion session tomorrow, Saturday, October 20, 2018. Immediately following the presentation and lifting of the embargo on publication of the data, the Company will report these additional results in a press release.

Prof. Manuel Hidalgo, MD, PhD, Professor of Medicine at Harvard Medical School, Chief of Hematology Oncology and Co-Director, Pancreatic Cancer Research Program, at Beth Israel Deaconess Hospital, and principal investigator of this study, said, "Metastatic pancreatic cancer remains an area of very high unmet medical need, as currently approved treatments are limited by poor response rates and survival. Despite recent advances in cancer treatment with immune checkpoint inhibitors in many tumor types, pancreatic cancer remains refractory to these treatment options. It is therefore encouraging to see that the combination of BL-8040 and KEYTRUDA shows promising clinical activity, a robust pharmacodynamic effect and a very good safety and tolerability profile. I look forward to the next phase of this study, in which chemotherapy will be added to the combination of BL-8040 and KEYTRUDA in an expansion cohort. I believe that the addition of chemotherapy may boost the clinical response rate, while hopefully maintaining the favorable safety and tolerability profile observed in this arm of this trial."

"We are extremely pleased with the top-line results from this ongoing study," stated Philip Serlin, Chief Executive Officer of BioLineRx. "These data, which demonstrate that the combination of BL-8040 and KEYTRUDA is safe, with encouraging signs of clinical activity and proof of concept for the mechanism of action, support the combination’s potential to become an effective immunotherapy regimen for pancreatic cancer – a disease that has responded very poorly to available treatments, including immunotherapy. We look forward to expanding our collaboration with MSD and maximizing the potential of this combination through an additional study arm that will add chemotherapy to the regimen. We believe the addition of chemotherapy may be synergistic with the existing combination, as chemotherapy has been shown to reduce overall tumor burden while inducing immunogenic cell death, leading to activation and expansion of new tumor-reactive T-cells. Based on its demonstrated mechanism of action, we believe BL-8040 can facilitate the infiltration of these T-cells into the tumor core, alongside the restoration of T-cell activity within the tumor by KEYTRUDA. We look forward to commencing the triple combination arm of this important study by the end of this year, with results expected in the second half of 2019."

About the COMBAT/KEYNOTE-202 Study

The Phase 2a COMBAT/KEYNOTE-202 study is currently 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., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in over 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, and is being carried out in the US, Israel and additional territories. The study is being conducted by BioLineRx under a collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary, to support a Phase 2a program investigating BioLineRx’s BL-8040 in combination with KEYTRUDA in patients with metastatic pancreatic cancer.

In July 2018, the Company announced the expansion of its immuno-oncology collaboration with MSD to include a triple combination arm investigating the safety, tolerability and efficacy of BL-8040, KEYTRUDA and chemotherapy. The triple combination arm will focus on second-line pancreatic cancer patients. Thirty to fifty patients will be enrolled in this arm, planned for initiation in the fourth quarter of 2018.

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 to peripheral blood and to be effective at inducing direct tumor cell death. In addition, clinical findings have demonstrated the ability of BL-8040 to mediate infiltration of T-cells into tumors that were previously immunologically "cold" and devoid of immune cell infiltrate. Immune checkpoint inhibitors (such as KEYTRUDA) produce anti-cancer effects by increasing the activity of T-cells through blockade of the interaction between the immune checkpoint receptor PD-1, on T-cells, and its ligand PD-L1, on tumor cells. Pancreatic cancers have very little T-cell infiltrate, making them less susceptive to checkpoint blockade than other tumors that are infiltrated by T-cells. Therefore, combining BL-8040 with immune checkpoint blockade is predicted to increase the responsiveness of pancreatic cancer patients to immunotherapy. Further increase in the sensitivity of pancreatic cancer cells to BL-8040 and KEYTRUDA may be achieved by chemotherapy-mediated immunogenic cell death and exposure of new tumor antigens, resulting in activation of new anti-cancer T cell clones.

About BL-8040

BL-8040 is a short synthetic peptide for the treatment of hematological malignancies, solid tumors, and stem cell mobilization. It functions as a high-affinity best-in-class 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, sensitization of cancer cells to chemo- and bio-based anti-cancer therapies, and direct anti-cancer effect by inducing programmed cell death (apoptosis). BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On October 19, 2018 Novartis reported Phase II preliminary results of the GEOMETRY mono-1 clinical trial of investigational MET inhibitor capmatinib (INC280) in 94 adult patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon-14 skipping mutations (Press release, Novartis, OCT 19, 2018, View Source [SID1234529978]). The GEOMETRY mono-1 study showed an overall response rate (ORR) of 72.0% (95% CI: 50.6-87.9) in treatment-naive patients and 39.1% (95% CI: 27.6-51.6) in previously treated patients. ORR was assessed by blinded independent review committee (BIRC). Adverse events (AEs) were consistent with previously reported data and no new safety signals were observed. Results of the Phase II study were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress [October 19, 2018 at 4:45 PM CET] (Abstract #LBA52)[1].

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"These preliminary findings reveal the potential of capmatinib in MET exon-14 skipping mutated NSCLC patients. Compared to the previously treated patient groups, the primary advantage in terms of overall response rate reported in treatment-naive patients highlights the clinical relevance for an earlier diagnostic testing and prompt treatment of this challenging patient population," said Juergen Wolf, MD, University Hospital Cologne.

NSCLC is the most common type of lung cancer, impacting more than 2 million people per year[2]. Approximately 3-4% of all patients with NSCLC have an identified MET mutation[3]. Though rare, this mutation is an indicator of especially poor prognosis and there is currently no approved therapy designed to target this mutation[4].

"Patients diagnosed with advanced MET mutated NSCLC represent an unmet medical need and often face a poor prognosis," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "We are encouraged by the GEOMETRY mono-1 results and the potential for capmatinib to help patients with this disease."

About GEOMETRY mono-1
The GEOMETRY mono-1 trial is a multicenter, open-label, phase II study to evaluate the efficacy and safety of single-agent INC280 in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with MET exon-14 skipping were assigned to Cohorts 4 (previously treated patients) or 5B (treatment naive) regardless of MET amplification/gene copy number (centrally confirmed), and received 400 mg capmatinib tablets twice daily. The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=25) of 72.0% (95% CI: 50.6-87.9) and an ORR in the previously treated patients (n=69) of 39.1% (95% CI: 27.6-51.6). DOR was not reached by the time of analysis, indicating sustainability of response[1],[6].

The most common treatment-related AEs included peripheral edema, nausea, vomiting, and increased blood creatinine levels. Of patients treated with INC280, 83.8% experienced an AE, with 33.1% having grade 3/4 AEs[1],[6].

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor licensed to Novartis by Incyte Corporation in 2009. Under the Agreement, Incyte granted Novartis exclusive Development and Commercialization worldwide rights to this MET inhibitor compound and certain back-up compounds in all indications.

Novartis Commitment to Lung Cancer
Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and over 2 million new cases of lung cancer are diagnosed each year[2]. Among patients with NSCLC, almost 70% have an actionable mutation that may be targeted with available therapies[7]. To determine the most appropriate treatment, medical organizations recommend genomic testing for patients with lung cancer[8].

Novartis Oncology’s research in NSCLC has helped transform treatment approaches for patients living with mutation-driven diseases, among others. Novartis continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds that target genetic biomarkers in NSCLC.

On October 19, 2018 Incyte (NASDAQ:INCY) reported Phase 2 preliminary results of the GEOMETRY mono-1 clinical trial of investigational MET inhibitor capmatinib in 94 adult patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon-14 skipping mutations (Press release, Incyte, OCT 19, 2018, View Source [SID1234529977]). The GEOMETRY mono-1 study showed an overall response rate (ORR) of 72.0 percent (95% CI: 50.6-87.9) in treatment-naive patients and 39.1 percent (95% CI: 27.6-51.6) in previously treated patients. ORR was assessed by blinded independent review committee (BIRC). Adverse events (AEs) were consistent with previously reported data and no new safety signals were observed.

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Results of the Novartis-sponsored Phase 2 study were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress (October 19, 2018 at 4:45 p.m. CEST / 10:45 a.m. EDT, Abstract LBA52).1

"These preliminary findings reveal the potential of capmatinib in MET exon-14 skipping mutated NSCLC patients. Compared to the previously treated patient groups, the primary advantage in terms of overall response rate reported in treatment-naive patients highlights the clinical relevance for an earlier diagnostic testing and prompt treatment of this challenging patient population," said Juergen Wolf, M.D., University Hospital Cologne, Germany.

NSCLC is the most common type of lung cancer, impacting more than 2 million people per year.2 Approximately 3-4 percent of all patients with NSCLC have an identified MET mutation.3 Though rare, this mutation is an indicator of especially poor prognosis and there is currently no approved therapy designed to target this mutation.4

"We are very pleased to announce these promising, preliminary results for capmatinib, another investigational medicine invented at Incyte that has the potential to be the first MET-selective targeted agent approved by the FDA," said Steven Stein, M.D., Chief Medical Officer, Incyte. "We are encouraged by the results of this study and the potential for capmatinib to help patients with advanced MET mutated NSCLC, who face a poor prognosis and represent a clear unmet medical need."

About GEOMETRY mono-1

The GEOMETRY mono-1 trial is a multicenter, open-label, Phase 2 study to evaluate the efficacy and safety of single-agent capmatinib (INC280) in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with MET exon-14 skipping were assigned to Cohorts 4 (previously treated patients) or 5B (treatment naive) regardless of MET amplification/gene copy number (centrally confirmed), and received 400 mg capmatinib tablets twice daily. The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=25) of 72.0 percent (95% CI: 50.6-87.9) and an ORR in the previously treated patients (n=69) of 39.1 percent (95% CI: 27.6-51.6). DOR was not reached by the time of analysis, indicating sustainability of response.1,6

The most common treatment-related AEs included peripheral edema, nausea, vomiting and increased blood creatinine levels. Of patients treated with capmatinib, 83.8 percent experienced an AE, with 33.1 percent having grade 3/4 AEs.1,6

About Capmatinib

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor invented at Incyte that was licensed to Novartis in 2009. Under the Agreement, Incyte granted Novartis exclusive development and commercialization worldwide rights to this MET inhibitor compound and certain back-up compounds in all indications. Novartis has stated that it expects to submit a new drug application to the U.S. Food and Drug Administration for capmatinib as a treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring MET amplification and/or mutations in 2019. If capmatinib is successfully developed by Novartis, Incyte may become eligible for over $500 million in future milestones as well as royalties of between 12 percent and 14 percent on global sales by Novartis.

On October 19, 2018 SELLAS Life Sciences Group Inc., (Nasdaq: SLS) (SELLAS or the Company), a clinical-stage biopharmaceutical company focused on novel cancer immunotherapies for a broad range of cancer indications, reported that the independent Data Safety Monitoring Board (DSMB) unanimously concluded that the final data from the Phase 2b study of trastuzumab (TZ, Herceptin) +/- nelipepimut-S (NPS, NeuVax) in HER2 1+/2+ breast cancer patients confirms the previously announced findings from the interim analysis of this study (Press release, Sellas Life Sciences, OCT 19, 2018, View Source [SID1234529976]). The DSMB concluded that there was an incremental improvement in the outcomes and statistics with a longer median follow-up (more than 7 months; 26.1 months at final vs. 18.8 months at interim analysis). The final analysis showed no new safety signals and continued to show no difference in cardiotoxicity between TZ + NPS compared to TZ alone. Finally, the DSMB confirmed that the final analysis continues to identify patients with triple negative breast cancer (TNBC) as the key target patient population for development of the NPS + TZ combination in the adjuvant setting in early-stage HER2 1+/2+ breast cancer patients.

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On March 28, 2018, based on a pre-specified interim analysis and the positive TNBC results, the DSMB had recommended to expeditiously seek regulatory guidance by the U.S. Food and Drug Administration (FDA) for further development of the combination of NPS + TZ in TNBC, a population with large unmet medical need.

SELLAS will host a conference call at 8:00 a.m. ET on October 22, 2018, following the oral presentation at the ESMO (Free ESMO Whitepaper) 2018 Annual Meeting of the interim and updated final clinical data from its Phase 2b trial of the combination of trastuzumab (Herceptin) +/- nelipepimut-S (NPS, NeuVax) targeting HER2 low-expressing breast cancer patient cohorts. Management and invited Key Opinion Leaders, Dr. Elizabeth Mittendorf, MD, PhD and Dr. George Peoples, MD, FACS, will participate in the conference call.

Conference Call Details for Monday, October 22, 2018 at 8:00 a.m. ET:

To participate in the conference call, please dial (866) 416-7995 (domestic) or +1 (409) 217-8225 (international) and refer to conference ID 5571389. A live webcast of the call can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.sellaslifesciences.com.

An archived webcast recording will be available on the SELLAS website beginning approximately two hours after the call.

Details for the ESMO (Free ESMO Whitepaper) presentation are as follows:
Title:Pre-specified interim analysis of a randomized phase 2b trial of trastuzumab + nelipepimut-S (NeuVax) vs trastuzumab for the prevention of recurrence demonstrates benefit in triple negative (HER2 low-expressing) breast cancer patients
Date and Time: 22 October, 2018; 11:54 am Central European Time (5:54 am ET)
Location: Hall A2 – Room 18; Messe Munich Congress Venue, Munich, Germany

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

About ESMO (Free ESMO Whitepaper)

The European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) is Europe’s leading non-profit medical oncology organization. ESMO (Free ESMO Whitepaper) is a membership-based society, comprising of 500 expert committee members and 18,000 oncology professionals. ESMO (Free ESMO Whitepaper) organizes a large number of meetings to provide its members and the community with the resources they need and also plays a major role in public policy and European affairs. The ESMO (Free ESMO Whitepaper) 2018 Annual Meeting represents a multi-professional platform for oncology education and exchange, and for immense international visibility for scientific research, and will be held under the tagline "Securing access to optimal cancer care."

On October 19, 2018 ArQule, Inc. (Nasdaq:ARQL) reported the presentation of preliminary clinical data on miransertib (ARQ 092) in three poster presentations at the American Society of Human Genetics (ASHG) 2018 Annual Meeting held from October 16 to 20, 2018 in San Diego (Press release, ArQule, OCT 19, 2018, View Source [SID1234529975]). The data presented relate to patients affected by either Proteus syndrome or PROS who have been receiving miransertib as part of a clinical trial or in a compassionate use setting.

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Two presentations feature data from two patients treated as part of ArQule’s named patient/compassionate use program. Presentation highlights include:

1.Personalized medicine in rare diseases and cancer: A case report of a lasting response in a young teenage patient with Proteus syndrome and secondary ovarian cancer

Treatment for the Proteus syndrome patient with concomitant relapsed ovarian cancer was administered at a dose level of 100mg and was well tolerated for over 19 months, resulting in a clinically significant/durable partial response of tumor and improvement of Proteus syndrome symptoms including improved mobility/bone changes
2.Severe PI3Kinase overgrowth syndrome treated with the AKT inhibitor miransertib

Treatment for the PROS patient was well tolerated for over 25 months resulting in clinical stabilization and radiological improvement of disease
"Our understanding of the potential for miransertib to target and treat these rare and devastating diseases that arise due to genetic alterations of the PI3K/AKT pathway has grown significantly since we partnered with The National Human Genome Research Institute in 2015 to conduct the first clinical trial in Proteus syndrome," said Brian Schwartz, M.D., Chief Medical Officer of ArQule. "The data we are presenting at ASH (Free ASH Whitepaper)G continues to highlight the promise of ArQule’s precision medicine approach for both rare diseases and oncology. We remain deeply committed to advancing miransertib for rare PI3K/AKT pathway overgrowth diseases as rapidly as possible, as there are currently no approved therapeutics for these patients."

A third presentation features data from patients treated as part of ArQule’s ongoing Phase 1/2, open label study of miransertib for the treatment of PROS. Study objectives include the evaluation of dosing schedule, safety, PK profile and preliminary efficacy of miransertib. Presentation highlights include:

3.An open-label, phase 1/2 study of miransertib (ARQ 092), an oral pan-AKT inhibitor, in patients (pts) with PIK3CA-related Overgrowth Spectrum (PROS): Preliminary results

Preliminary evidence of clinical efficacy was demonstrated by improvements in disease related symptoms and objective radiologic and photographic measures
Miransertib was well tolerated with a demonstrated manageable toxicity profile in patients as young as two years old
The recommended dose of miransertib, defined as 15 mg/m2 QD, with potential dose escalation to 25 mg/m2 QD, provided appropriate inhibition of the activated PIK3CA pathway for long-term use without inhibition of growth in normal healthy cells
Peter Lawrence, President and Chief Operating Officer of ArQule said: "This initial presentation of clinical data from our Phase 1/2 study in PROS lays the foundation for potentially expanding the miransertib rare disease program beyond Proteus syndrome, for which the drug already has received Rare Pediatric Disease and Fast Track Designation. We look forward to continuing our productive discussions with regulators to define a pivotal trial design and rapidly advance miransertib."

All posters presented by ArQule at the ASH (Free ASH Whitepaper)G 2018 Annual Meeting are available on the company’s website at View Source

About Miransertib
Miransertib (ARQ 092) is an orally available, selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2 and 3 isoforms. Dysregulation of AKT has been implicated in a variety of rare overgrowth diseases and cancers; however, there are currently no approved inhibitors of AKT. AKT inhibitors, either as single agent or combination therapy, show significant promise in molecularly defined patient populations. Miransertib is currently in a Phase 1/2 company-sponsored study for PIK3CA-Related Overgrowth Spectrum (PROS), a Phase 1 study for ultra-rare Proteus syndrome conducted by the National Institutes of Health (NIH/NHGRI), and a Phase 1b study in combination with the hormonal therapy, anastrozole, in patients with advanced endometrial cancer with AKT and PI3K mutations. Miransertib has been granted Rare Pediatric Disease Designation and Fast Track Designation by the U.S. Food and Drug Administration (FDA), as well as Orphan Designation by the FDA and European Medicines Agency in the rare overgrowth disease, Proteus syndrome.

About PROS
PROS is a term used to refer to a spectrum of rare diseases identified by somatic mutations in the PIK3CA gene, that result in excess growth in certain areas of the body. While the individual diseases that fall within the overgrowth spectrum have similar symptoms, each disease is defined by unique clinical characteristics. The implementation of genetic sequencing has led to the identification of the underlying genetic mutations that drive these overgrowth disorders, allowing for the development of medicines that target the specific causes of disease.

About Proteus Syndrome
Proteus syndrome is an ultra-rare condition characterized by the aberrant overgrowth of multiple tissues of the body. Patients with Proteus syndrome experience changes in the shapes of certain body structures over time, including abnormal, often asymmetric, massive growth (overgrowth) of the skeleton, skin, adipose tissue and central nervous system out of proportion to the rest of the body. Although patients may have minimal or no manifestations at birth, the disease develops and becomes apparent in early childhood (6-18 months) and rapidly progresses with intense growth in the first 10 years of life. The worldwide incidence is believed to be approximately one in a million. There are currently no approved medicinal treatments for Proteus syndrome, leaving patients with minimal treatment options to manage the disease and a mortality of 25% by age 22.