On October 19, 2018 Clovis Oncology, Inc. (NASDAQ: CLVS) reported initial data from its ongoing Phase 2 TRITON2 clinical trial of Rubraca at the ESMO (Free ESMO Whitepaper) 2018 Congress (European Society for Medical Oncology) (Press release, Clovis Oncology, OCT 19, 2018, View Source [SID1234529983]). The data show a 44% confirmed objective response rate (ORR) by investigator assessment in 25 RECIST* /PCWG3** response-evaluable patients with a BRCA1/2 alteration. The median duration of response in these patients has not yet been reached. In addition, a 51% confirmed prostate specific antigen (PSA) response rate was observed in 45 PSA response-evaluable patients with a BRCA1/2 alteration.

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The TRITON2 results were the basis for Breakthrough Therapy designation for Rubraca as a monotherapy treatment of adult patients with BRCA1/2 mutated mCRPC who have received at least one prior androgen receptor (AR)-directed therapy and taxane-based chemotherapy, which was granted on October 2, 2018 by the U.S. Food and Drug Administration (FDA). These data will be highlighted in a poster authored by Dr. Wassim Abida, Medical Oncologist, Memorial Sloan Kettering Cancer Center, and principal investigator for the TRITON2 study. The data have been selected for a poster discussion session that will be led by invited discussant Dr. Joaquin Mateo, of the Prostate Cancer Translational Research Group, Vall d’Hebron Institute of Oncology (VHIO) on 21 October at 09:15-9:40 CEST.

"Rubraca has previously demonstrated antitumor activity in its approved indications for women with advanced ovarian cancer," said Dr. Abida. "These new data show that Rubraca may also offer a new approach for the treatment of mCRPC associated with BRCA1 and BRCA2 alterations, with the potential to achieve a clinical response in patients with few remaining therapy options."

Patients enrolled in the TRITON2 study had received prior treatment with at least one androgen receptor (AR)-directed therapy and taxane-based chemotherapy and were screened for a deleterious germline or somatic alteration in BRCA1, BRCA2 or one of 13 other pre-specified homologous recombination (HR) genes. Study participants were allocated into three cohorts based on the type of gene alteration and disease status, which was determined by genomic sequencing and RECIST criteria, respectively. Each cohort received 600mg Rubraca twice daily and were grouped based on the following criteria: A) alteration in either BRCA1, BRCA2 or ATM genes, with tumors that can be measured with visceral and/or nodal disease; B) alteration in either BRCA1, BRCA2 or ATM genes, with tumors that cannot be measured with visceral and/or nodal disease, or C) alteration in another HR gene associated with sensitivity to PARP inhibition, with or without measurable disease. The primary study endpoints include confirmed ORR per RECIST/PCWG3 in patients with measurable disease at baseline and PSA response in patients with no measurable disease at baseline. Secondary endpoints include overall survival (OS), clinical benefit rate, and safety and tolerability.1

As of the visit cut-off date of June 29, 2018, 85 patients were treated with Rubraca; the overall median treatment duration was 3.7 (range, 0.5–12.9) months and median follow up was 5.7 (range, 2.6–16.4) months. The median treatment duration in patients with a BRCA1/2 alteration was 4.4 months (range, 0.5-12.0 months). Forty-six patients (54.1%) were evaluable for RECIST/PCWG3 response, including 25 patients with a BRCA1/2 alteration. By investigator-assessed RECIST/PCWG3, the confirmed ORR in patients with a BRCA1/2 alteration treated with Rubraca was 44.0% (11/25). Among the 45 evaluable patients with a BRCA1/2 alteration, 51.1% (23/45) had a confirmed PSA response (95% CI, 35.8–66.3).

Overall, the most common treatment-emergent adverse events (TEAEs) of any grade (CTCAE Grade 1-4) in all patients regardless of causality included asthenia/fatigue (44.7%, or 38/85), nausea (42.4%, or 36/85), anemia/decreased hemoglobin (22.4%, or 19/85) and constipation (28.2%, or 24/85). Five patients (5.9%) discontinued therapy due to a non-progression TEAE. One patient died due to disease progression.1

"We are very encouraged by these initial findings from the TRITON2 study, which demonstrate the potential of Rubraca to treat men with advanced prostate cancer whose disease has progressed after receiving multiple prior lines of therapy," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "PARP inhibitors are now a validated therapeutic class in oncology in multiple tumor types, and these new data underscore the benefit that Rubraca may provide for men with advanced, BRCA-mutant castration-resistant prostate cancer. Having recently received Breakthrough Therapy designation based on these data, we are committed to the rapid development of Rubraca for men with this very difficult-to-treat disease."

The poster discussion session also will include the first presentation of genomic profiling data based on tumor tissue and plasma cfDNA samples from the TRITON clinical program. The poster, authored by Dr. Simon Chowdhury, Consultant Medical Oncologist, Guy’s Hospital & Sarah Cannon Research Institute and co-principal investigator for the TRITON clinical studies, will be included in the same poster discussion session as the TRITON2 data, led by invited discussant Dr. Joaquin Mateo, of the Prostate Cancer Translational Research Group, Vall d’Hebron Institute of Oncology (VHIO). The poster discussion session takes place on 21 October at 09:15-9:40 CEST.

The data suggest cfDNA detected from plasma can be used to identify deleterious HR gene alterations in a manner that is less invasive than tumor tissue testing. Additionally, due to the invasiveness of tumor tissue sample collection, archival primary prostate samples are often used, and data suggest these samples are not representative of the somatic alterations which emerge in mCRPC.

In the study evaluation, patients’ HR gene alteration status was determined by screening a total of 1,311 tumor and 638 plasma specimens, collected from a total of 1,516 patients to determine eligibility for TRITON2 and TRITON3. There was high concordance (74%) in identifying patients with deleterious BRCA1/2 mutations by both tissue and plasma sample. The results demonstrate that detecting genetic alterations within HR genes using cfDNA sequencing could prove to be a convenient method to identify patients who might be suitable candidates for treatment with Rubraca.2 Approximately 12% of men screened for the TRITON2 study were identified as having a BRCA1/2 alteration by plasma screening.

"Tumor tissue testing relies heavily on archival samples taken when a patient is newly diagnosed but may not capture all the alterations that emerge in patients with metastatic disease," said Dr. Chowdhury. "The screening data demonstrate that there is a high concordance between alterations detected in the tissue and plasma assays. Due to the less invasive nature of obtaining cfDNA through plasma testing, this method may be more suitable for both physicians and patients and may also identify more patients eligible for clinical trials of Rubraca."

Clovis’ Rubraca poster presentations will be available online at clovisoncology.com at 07:30 CEST on Saturday, October 20, 2018.

About the TRITON2 Clinical Study

TRITON2 is an international, multicenter, open-label, Phase 2 study of Rubraca in men with metastatic castration-resistant prostate cancer with BRCA gene alterations (inclusive of germline or somatic), which is also enrolling patients with deleterious alterations of other homologous recombination (HR) repair genes, including ATM. The study is currently enrolling across sites worldwide. For more information, please visit www.tritontrials.com.

About Prostate Cancer

The American Cancer Society estimates that more than 164,000 men in the United States will be diagnosed with prostate cancer in 2018,3 and the GLOBOCAN Cancer Fact Sheets estimate that approximately 345,000 men in Europe were diagnosed with prostate cancer in 2012.4 Castration-resistant prostate cancer has a high likelihood of developing metastases. Metastatic castration-resistant prostate cancer, or mCRPC, is an incurable disease, usually associated with poor prognosis. According to the American Cancer Society, the five-year survival rate for mCRPC is approximately 29%.5 Approximately 12% of mCRPC patients have a deleterious mutation in BRCA1 or BRCA2, according to an article published in the Journal of Clinical Oncology Precision Oncology in 2017.6 These molecular markers may be used to select patients for treatment with a PARP inhibitor.

About Rubraca

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for Rubraca. Rubraca is an unlicensed medical product outside of the U.S. and Europe.

Rubraca EU Authorized Use

Rubraca is licensed for adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Click here to access the current Summary of Product Characteristics. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

Rubraca U.S. FDA Approved Indications and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated as monotherapy for the treatment of adult patients with deleterious BRCA mutations (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur uncommonly in patients treated with Rubraca, and are potentially fatal adverse reactions. In approximately 1100 treated patients, MDS/AML occurred in 12 patients (1.1%), including those in long-term follow-up. Of these, five occurred during treatment or during the 28-day safety follow-up (0.5%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 28 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA-damaging agents. Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1).

Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose (see Dosage and Administration [2.2] in full Prescribing Information) and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample cytogenetic analysis. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1–4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%) and neutropenia (20%).

Most common laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1–4) were increase in creatinine (98%), decrease in hemoglobin (88%), increase in cholesterol (84%), increase in alanine aminotransferase (ALT) (73%), increase in aspartate aminotransferase (AST) (61%), decrease in platelets (44%), decrease in leukocytes (44%), decrease in neutrophils (38%), increase in alkaline phosphatase (37%) and decrease in lymphocytes (29%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1–4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%) and thrombocytopenia (21%).

Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%; Grade 1–4) were increase in creatinine (92%), increase in alanine aminotransferase (ALT) (74%), increase in aspartate aminotransferase (AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes (45%), increase in cholesterol (40%), decrease in platelets (39%) and decrease in absolute neutrophil count (35%).

Co-administration of Rubraca can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring. Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.

Click here for full Prescribing Information and additional Important Safety Information.

On October 19, 2018 GRAIL, Inc., a healthcare company focused on the early detection of cancer, reported that new data from the Circulating Cell-free Genome Atlas (CCGA) study will be presented by Minetta Liu, MD, Research Chair and Professor, Department of Oncology, Mayo Clinic, in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress taking place October 19 – 23 in Munich, Germany (Press release, Grail, OCT 19, 2018, View Source [SID1234529982]).

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CCGA is a prospective, observational, longitudinal study of approximately 15,000 participants. In the first CCGA sub-study, three prototype genome sequencing assays were used to analyze blood samples from 2,800 participants. Data from approximately 1,800 of these participants were presented earlier this year at the 2018 annual meetings of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) and American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).1,2

The new data being presented at ESMO (Free ESMO Whitepaper) are results from the 1,010 remaining participants from the same sub-study, which were analyzed separately for verification of the initial results. Results between the two data sets were similar, showing the prototype assays consistently detected strong signals in participants’ blood samples at high specificity for multiple cancer types. Slides with detailed results will be posted on GRAIL’s website after the presentation at grail.com/science/publications.

Presentation Details

Abstract 50O

Plasma cell-free DNA (cfDNA) assays for early multi-cancer detection: the Circulating Cell-free Genome Atlas (CCGA) study
Proffered Paper (Oral Presentation): Saturday, October 20, 2018: 9:15 – 9:27 CEST, ICM – Room 14b

About the First CCGA Sub-Study

In this pre-planned sub-study of CCGA, three prototype genome sequencing assays were evaluated as potential methods for a blood-based test for early cancer detection. Blood samples from 2,800 participants (1,628 participants with newly diagnosed cancer who had not yet received treatment and 1,172 participants without a cancer diagnosis) were sequenced with all three prototype assays. Twenty different cancer types across all stages were included in the sub-study. Blood samples from the 2,800 participants were separated into a training set (1,785 participants) and an independent test set (1,010 participants) for verification of the initial results.

The prototype sequencing assays included:

Targeted sequencing of paired cell-free DNA (cfDNA) and white blood cells to detect somatic mutations, such as single nucleotide variants and small insertions and/or deletions;
Whole-genome sequencing of paired cfDNA and white blood cells to detect somatic copy number changes; and
Whole-genome bisulfite sequencing of cfDNA to detect abnormal cfDNA methylation patterns.
About CCGA

CCGA is a prospective, observational, longitudinal study designed to characterize the landscape of cell-free nucleic acid (cfNA) profiles in people with and without cancer. The planned enrollment for the study is more than 15,000 participants across 142 sites in the United States and Canada. Approximately 70 percent of participants will have cancer at the time of enrollment (newly diagnosed, have not yet received treatment) and 30 percent will not have a known cancer diagnosis. Planned follow-up for all participants is at least five years to collect clinical outcomes.

On October 19, 2018 Cytokinetics, Incorporated (Nasdaq:CYTK) reported that it is scheduled to report third quarter results on November 1, 2018 at 4:00 PM Eastern Time (Press release, Cytokinetics, OCT 19, 2018, View Source [SID1234529981]). Following the announcement, Cytokinetics’ senior management will host a conference call at 4:30 PM Eastern Time to discuss operational and financial results and the company’s outlook for the future.

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The conference call will be simultaneously webcast and can be accessed from the homepage and in the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by dialing either (866) 999-CYTK (2985) (United States and Canada) or (706) 679-3078 (international) and typing in the passcode 9785146.

An archived replay of the webcast will be available via Cytokinetics’ website until November 8, 2018. The replay will also be available via telephone by dialing (855) 859-2056 (United States and Canada) or (404) 537-3406 (international) and typing in the passcode 9785146 from November 1, 2018 at 7:30 PM Eastern Time until November 8, 2018.

On October 19, 2018 Idera Pharmaceuticals, Inc. (NASDAQ: IDRA), a clinical-stage biopharmaceutical company focused on the development and ultimate commercialization of drug candidates for both oncology and rare disease indications characterized by small, well-defined patient populations with serious unmet needs, reported its data from the ongoing ILLUMINATE-204 trial investigating tilsotolimod, Idera’s intratumorally-delivered toll-like receptor 9 (TLR9) agonist, in combination with ipilimumab (Yervoy*) at the 2018 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Idera Pharmaceuticals, OCT 19, 2018, View Source [SID1234529980]).

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The poster, which was selected for a poster discussion session, highlighted additional analyses of data for 21 patients for whom efficacy and safety analysis were originally presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting this past June (data cut-off May 9th).

The new analyses address the potential of intramural tilsotolimod to induce an antitumor response in combination with ipilimumab in injected tumors as well as uninjected tumors via an abscopal effect. As previously reported the overall response rate (ORR, by RECIST 1.1) for these 21 patients was 39%. Notably, in 7 of the 8 responders tumor shrinkage was observed in both the injected and uninjected tumors. Tumor shrinkage at uninjected lesions was observed in an additional four patients who had not met the criteria for RECIST v.1.1 response status as of this analysis.

Clinical responses were seen in patients whose HLA-ABC RNA (MHC class I) expression is low at baseline. Rodig and colleagues1 have recently shown that robust MHC class I expression is required for anti-CTLA-4 activity. Our findings suggest that combining tilsotolimod with ipilimumab may overcome this resistance mechanism, and therefore, enhance clinical activity and increase the overall response rate compared to that expected with ipilimumab monotherapy.

The ILLUMINATE-204 trial is enrolling two distinct patient populations, both patients who are naïve to ipilimumab therapy (N=40; Primary Efficacy Endpoint Population) and patients who have prior ipilimumab experience (N=Up to 20; Secondary Efficacy Endpoint Population). Of the initial 21 patients available for efficacy evaluations 6 of 17 patients from the Primary Efficacy Endpoint Population and 2 of 4 patients from the Secondary Efficacy Endpoint Population achieved RECIST v.1.1 responses, further demonstrating a signal that tilsotolimod has the potential to help overcome prior ipilimumab resistance.

"The data presented at ESMO (Free ESMO Whitepaper) demonstrate that in patients with melanoma progressing on or after PD-1 inhibitor therapy, injecting a single tumor lesion with tilsotolimod, in combination with ipilimumab, produced tumor shrinkage in distant uninjected lesions in nearly all patients with reported responses by RECIST v1.1 criteria," stated Adi Diab, M.D., Lead Trial Investigator, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center. "Moreover, clinical responses were seen in tumors where MHC class I expression was low at baseline. In a recent clinical study in melanoma, it was shown that robust MHC class I expression is required for anti-CTLA-4 activity. Our findings suggest that combining tilsotolimod with ipilimumab may overcome this mechanism of resistance to anti-CTLA-4 monotherapy."

"The clear demonstration of tumor shrinkage in uninjected tumors following the injection of a single tumor lesion with tilsotolimod, provides clinical confirmation of our translational data and addresses an important frequently asked question," stated Joanna Horobin, Idera’s Chief Medical Officer. "Additionally, the new observation that tilsotolimod may overcome the requirement for MHC class 1 expression for effective anti-tumor therapy with ipilimumab in patients otherwise unlikely to respond, is a very exciting finding and addresses another important question regarding the contribution of tilsotolimod when given in combination with ipilimumab."

The poster discussion is scheduled for Saturday, October 20, 2018 at 2:45 PM CEST (8:45 AM EST) in Room ICM-14b at the Messe Munchen Congress Center in Munich, Germany.

In addition to the poster discussion, the company also presented a Trials in Progress (TiPS) poster on the trial design for the ongoing ILLUMINATE-301 Phase 3 clinical trial of the combination of tilsotolimod and ipilimumab for unresectable or metastatic melanoma following failure of PD-1 inhibitor treatment. This poster will be on display on Sunday, October 21, 2018 from 12:45 – 1:45 PM CEST (6:45 – 8:45 AM EST) in Hall A3 at the Messe Munchen Congress Center in Munich, Germany.

Copies of these poster presentations are currently available on Idera’s corporate website at View Source

4th Quarter Clinical Efficacy and Safety Update
Based on the timing of disease assessment visits, the company plans an additional data cut later this quarter for the ILLUMINATE-204 trial to provide an update on clinical efficacy and safety data for up to 35 patients, including overall response rate (ORR) for all patients as well as for the Primary and Secondary Efficacy Patient Populations.

About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of anti-PD-1 refractory melanoma, in combination with ipilimumab as well as orphan drug designation from the FDA for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors. Currently approved immuno-oncology treatments, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy. Intratumoral injections with tilsotolimod are designed to selectively enable the T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

About ILLUMINATE-204
The ILLUMINATE-204 study (2125-204) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda** (pembrolizumab) or Opdivo* (nivolumab) has failed. Melanoma is the most dangerous type of skin cancer. When it is metastatic, it means that the melanoma has spread to different parts of the body. ILLUMINATE-204 is a multi-center, two-arm Phase 1/2 study that tests the safety and effectiveness of tilsotolimod in combination with either ipilimumab (Yervoy) or pembrolizumab (Keytruda) for the treatment of patients with anti-PD-1 refractory metastatic melanoma.

For additional details about ILLUMINATE-204, please go to clinicaltrials.gov and search for study identifier NCT02644967.

About ILLUMINATE-301
The ILLUMINATE-301 study (2125-MEL-301) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda (pembrolizumab) or Opdivo (nivolumab) has failed. ILLUMINATE-301 is a global, multi-center, randomized Phase 3 study that compares the effectiveness and safety between two treatment groups: IMO-2125 combined with ipilimumab (Yervoy) versus ipilimumab given alone.

For additional details about ILLUMINATE-301, please go to clinicaltrials.gov and search for study identifier NCT03445533.

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as the lymphatic system, liver or other visceral organs (metastatic disease). Because melanoma occurs in younger individuals, the years of life lost to melanoma are also disproportionately high when compared with other cancers. Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.

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.