On October 21, 2018 Ipsen Biopharmaceuticals, an affiliate of Ipsen (Euronext: IPN; ADR: IPSEY), reported results from a retrospective, observational analysis examining the real-world dosing patterns of patients with metastatic pancreatic cancer (mPC) treated with ONIVYDE (irinotecan liposome injection), at this year’s European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual congress taking place in Munich, Germany, Oct. 19-23, 2018 (Press release, Ipsen, OCT 21, 2018, View Source [SID1234530015]).

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Using the Flatiron Health electronic health record (EHR)-derived database, a longitudinal and nationally representative database comprising patient-level structured and unstructured data that is curated via technology-enabled abstraction, researchers identified 257 metastatic pancreatic cancer patients (median age: 67y; IQR: 61–74) who received ONIVYDE + fluorouracil (5-FU) and leucovorin (LV) therapy between November 2015 to August 2017 and analyzed their treatment data to assess dose intensity (DI) over the first 6 weeks of treatment, dose modifications during treatment, and overall duration of exposure (DOE) to ONIVYDE.

The real-world analysis (Poster 735P) describes how ONIVYDE was incorporated in the treatment sequencing that contained prior gemcitabine in the treatment of metastatic pancreatic cancer. In this analysis, the mean dose intensity was 177.8 mg/m2 (SD: 74.9 mg/m2). The median dose at initiation was 69.4 mg/m2 (IQR: 56.7–70.2); the recommended dose for ONIVYDE is 70 mg/m2. In addition, median duration of exposure was 8.9 weeks (IQR: 3.9/19 weeks) in first and second line and 6.3 weeks (IQR: 3.4/12.1 weeks) in third or plus lines.

These results are generally consistent with the NAPOLI-1 trial, however, dose modifications in the real-world analysis were lower (27.2% vs 45% in NAPOLI-1). In the NAPOLI-1 phase 3 trial, dose intensity over 6 weeks and duration of exposure for combination therapy with ONIVYDE was 167.5 mg/m2 (SD 44.8) and 8.7 weeks (IQR: 5.4 – 22.0), respectively. Despite these real-world patients being older, having worse performance status and more prior lines of treatment than patients in NAPOLI-1, more than half (59.1%) of patients started ONIVYDE + 5-FU/LV treatment with the recommended ONIVYDE dose (70 mg/m2).

NAPOLI-1 is the largest global, phase 3, randomized, open-label, multicenter trial in patients (N=417) with metastatic pancreatic cancer whose disease had progressed following gemcitabine-based therapy. Patients in the NAPOLI-1 trial being treated with ONIVYDE in combination with fluorouracil (5-FU) and leucovorin (LV) had improved overall survival (OS; primary endpoint) vs 5-FU/LV (6.1 mos vs 4.2 mos; HR = 0.67, 95% CI 0.49–0.92; P = 0.012). ONIVYDE monotherapy had no effect on OS.

ONIVYDE can cause severe, life-threatening neutropenia and diarrhea (see complete Boxed Warning in full prescribing information). ONIVYDE can also cause severe and fatal Interstitial Lung Disease (ILD) and hypersensitivity reactions. These serious adverse events may require withholding or discontinuing treatment with ONIVYDE, a dose reduction and/or supportive treatment. The most common adverse reactions in NAPOLI-1 (≥20%) were diarrhea (59%), fatigue/asthenia (56%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), and pyrexia (23%).

"Patients are at the heart of what we do, with unmet need guiding our development strategy and driving how we innovate for patient care," said Dr. Sotirios Stergiopoulos, Senior Vice President, Head of Global Medical Affairs and Chief Medical Officer. "This real-world data analysis provides further evidence in support of the dose intensity and duration of exposure of ONIVYDE and 5-FU/LV observed in the NAPOLI-1 phase 3 trial. This retrospective analysis allows us to further understand how patients with pancreatic cancer are receiving and managing their treatment in real-world settings."

Dr. Afsaneh Barzi, Study Investigator, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, Calif., notes, "As a physician who treats patients with metastatic pancreatic cancer, I find it reassuring and welcome the unique evidence the Flatiron dosing analysis provides in demonstrating the real-world usage of ONIVYDE + 5-FU/LV in a large sample of metastatic pancreatic cancer patients being treated in a clinical oncology setting when compared to a clinical trial setting. Data from our real-world practice for clinical analysis serve to further our knowledge about how to continue to effectively treat our patients."

About Pancreatic Cancer

Pancreatic cancer is a rare and deadly disease with about 55,440 people (29,200 men and 26,240 women) being diagnosed with pancreatic cancer in the United States alone.1 More than half are diagnosed with metastatic disease, which has an overall 5-year survival rate of less than three percent (3%)1, and often rapidly progresses during or shortly after receiving chemotherapy.2 Pancreatic cancer accounts for about 3% of all cancers, and is the third leading cause of cancer-related death in the United States, surpassing breast cancer.1 It is expected to become the second leading cause of cancer-related death in the U.S. by the year 2030, surpassing colorectal cancer.1,3

About ONIVYDE

ONIVYDE is an encapsulated formulation of irinotecan. This long-circulating liposomal form is designed to increase length of tumor exposure to both irinotecan and its active metabolite, SN38. ONIVYDE is approved by the U.S. FDA, EMA and many other countries. In the U.S., ONIVYDE is approved for use in combination with fluorouracil (5-FU) and leucovorin (LV) for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. ONIVYDE is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas. Ipsen has gained exclusive commercialization rights for the current and potential future indications for ONIVYDE in the U.S., as well as the current licensing agreements with Servier for commercialization rights ex-U.S. and PharmaEngine for Taiwan.

IMPORTANT SAFETY INFORMATION:

WARNING: SEVERE NEUTROPENIA and SEVERE DIARRHEA

Fatal neutropenic sepsis occurred in 0.8% of patients receiving ONIVYDE. Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life- threatening neutropenia occurred in 20% of patients receiving ONIVYDE in combination with fluorouracil (5-FU) and leucovorin (LV). Withhold ONIVYDE for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment.

Severe diarrhea occurred in 13% of patients receiving ONIVYDE in combination with 5- FU/LV. Do not administer ONIVYDE to patients with bowel obstruction. Withhold ONIVYDE for diarrhea of Grade 2-4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity.

CONTRAINDICATION

ONIVYDE is contraindicated in patients who have experienced a severe hypersensitivity reaction to ONIVYDE or irinotecan HCl.

WARNINGS AND PRECAUTIONS

Severe Neutropenia: See Boxed WARNING. In patients receiving ONIVYDE/ 5-FU/LV, the incidence of Grade 3/4 neutropenia was higher among Asian (18/33 [55%]) vs White patients (13/73 [18%]). Neutropenic fever/neutropenic sepsis was reported in 6% of Asian vs 1% of White patients

Severe Diarrhea: See Boxed WARNING. Severe and life-threatening late-onset (onset >24 hours after chemotherapy [9%]) and early-onset diarrhea (onset ≤24 hours after chemotherapy [3%], sometimes with other symptoms of cholinergic reaction) were observed

Interstitial Lung Disease (ILD): Irinotecan HCl can cause severe and fatal ILD. Withhold ONIVYDE in patients with new or progressive dyspnea, cough, and fever, pending diagnostic evaluation. Discontinue ONIVYDE in patients with a confirmed diagnosis of ILD

Severe Hypersensitivity Reactions: Irinotecan HCl can cause severe hypersensitivity reactions, including anaphylactic reactions. Permanently discontinue ONIVYDE in patients who experience a severe hypersensitivity reaction

Embryo-Fetal Toxicity: ONIVYDE can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during and for 1 month after ONIVYDE treatment

ADVERSE REACTIONS

The most common adverse reactions (≥20%) were diarrhea (59%), fatigue/asthenia (56%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), and pyrexia (23%)
The most common Grade 3/4 adverse reactions (≥10%) were diarrhea (13%), fatigue/asthenia (21%), and vomiting (11%)
Adverse reactions led to permanent discontinuation of ONIVYDE in 11% of patients receiving ONIVYDE/5-FU/LV; The most frequent adverse reactions resulting in discontinuation of ONIVYDE were diarrhea, vomiting, and sepsis
Dose reductions of ONIVYDE for adverse reactions occurred in 33% of patients receiving ONIVYDE/5-FU/LV; the most frequent adverse reactions requiring dose reductions were neutropenia, diarrhea, nausea, and anemia
ONIVYDE was withheld or delayed for adverse reactions in 62% of patients receiving ONIVYDE/5-FU/LV; the most frequent adverse reactions requiring interruption or delays were neutropenia, diarrhea, fatigue, vomiting, and thrombocytopenia
The most common laboratory abnormalities (≥20%) were anemia (97%), lymphopenia (81%), neutropenia (52%), increased ALT (51%), hypoalbuminemia (43%), thrombocytopenia (41%), hypomagnesemia (35%), hypokalemia (32%), hypocalcemia (32%), hypophosphatemia (29%), and hyponatremia (27%)
DRUG INTERACTIONS

Avoid the use of strong CYP3A4 inducers, if possible, and substitute non-enzyme inducing therapies ≥2 weeks prior to initiation of ONIVYDE
Avoid the use of strong CYP3A4 or UGT1A1 inhibitors, if possible, and discontinue strong CYP3A4 inhibitors ≥1 week prior to starting therapy

On October 21, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that updated phase 1 safety and efficacy data for [fam-] trastuzumab deruxtecan, an investigational HER2 targeting antibody drug conjugate (ADC), were presented for a subgroup of patients with heavily pretreated HER2 expressing colorectal cancer at the 2018 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Munich, Germany (Press release, Daiichi Sankyo, OCT 21, 2018, https://www.prnewswire.com/news-releases/daiichi-sankyo-presents-updated-results-of-fam–trastuzumab-deruxtecan-ds-8201-in-patients-with-her2-expressing-advanced-colorectal-cancer-at-2018-european-society-for-medical-oncology-esmo-congress-300734400.html [SID1234530016]).

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An updated subgroup analysis in 19 evaluable patients with heavily pretreated HER2 expressing (defined as IHC ≥1+ or amplified) colorectal cancer receiving a recommended expansion dose of 6.4 mg/kg showed that [fam-] trastuzumab deruxtecan demonstrated a confirmed overall response rate of 15.8 percent (3 of 19 patients) and a disease control rate of 84.2 percent (16 of 19 patients). Median duration of response has not been reached and median progression-free survival was 3.9 months (95 percent CI: 2.1, 8.3) for this subgroup of patients. These patients had tumors with varying degrees of HER2 expression based on central IHC assessment of archival tissue, including six patients with HER2 IHC of zero (0). Tumor shrinkage primarily was observed in tumors with higher levels of HER2 IHC.

"We are encouraged by these preliminary results with [fam-] trastuzumab deruxtecan, particularly given the unmet medical need for patients with HER2 expressing colorectal cancer that has progressed on one or more prior therapies," said Takayuki Yoshino, MD, PhD, Director of Gastroenterology and Gastrointestinal Oncology at National Cancer Center Hospital East, Kashiwa, Japan, a study investigator. "These initial findings support further evaluation of [fam-] trastuzumab deruxtecan in this specific type of colorectal cancer."

"There are no therapies specifically approved for patients with HER2 expressing colorectal cancer, and continued study of [fam-] trastuzumab deruxtecan will provide a better understanding of the potential role of a HER2 targeting antibody drug conjugate in these patients," said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global Team Leader, Oncology Research and Development, Daiichi Sankyo. "Patient enrollment is underway into our global phase 2 study evaluating safety and efficacy of [fam-] trastuzumab deruxtecan in patients with HER2 expressing advanced colorectal cancer."

Updated overall safety data as of August 10, 2018 across all subgroups of the ongoing phase 1 study with [fam-] trastuzumab deruxtecan in various HER2 expressing cancers were also reported at ESMO (Free ESMO Whitepaper). Among 259 patients who received at least one dose of [fam-] trastuzumab deruxtecan 5.4 or 6.4 mg/kg in Part 1 or Part 2 of the study (regardless of tumor type), the most common adverse events (≥30 percent, any Grade) included nausea (74.1 percent), decreased appetite (56.8 percent;) vomiting (43.6 percent), anemia (37.8 percent), alopecia (37.5 percent), fatigue (34.0 percent), diarrhea (33.6 percent) and constipation (32.8 percent). A total of 54.1 percent of patients experienced a ≥ Grade 3 adverse event and 22.8 percent had a serious adverse event, including 4.6 percent of patients who experienced an adverse event that led to death. As previously presented, five cases of Grade 5 interstitial lung disease (ILD)/pneumonitis were reported by the investigators for the overall population of the phase 1 study, none of which was observed in patients with colorectal cancer. Any reported cases of ILD/pneumonitis in the [fam-] trastuzumab deruxtecan clinical development program are evaluated by an independent adjudication committee.

Unmet Need in Colorectal Cancer
Colorectal cancer is the third most common cancer worldwide. In 2012, there were approximately 1.36 million new cases diagnosed and 690,000 deaths worldwide.1 Approximately 25 percent of patients have metastatic disease at diagnosis, meaning the disease has spread to distant organs, and about 50 percent of patients with colorectal cancer will eventually develop metastases.2 Prognosis for these patients remains poor.3

An increase in the number of approved targeted therapies for advanced colorectal cancer over the past decade has helped improve outcomes for some patients, however efficacy and tolerability of second and third-line treatments remain limited.4,5,6,7,8 Approximately 3 percent of colorectal cancers overexpress the HER2 protein, which is a well-established therapeutic target in breast and gastric cancer.4 In addition, research indicates that HER2 amplification may be associated with resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy and shorter survival.9,10 Currently, no approved HER2 targeting therapies exist for patients with colorectal cancer.

About the [Fam-] Trastuzumab Deruxtecan Phase 1 Study
An open-label, two-part phase 1 study is currently evaluating [fam-] trastuzumab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of this study was to assess the safety and tolerability of [fam-] trastuzumab deruxtecan and determine the maximum tolerated dose. Data from this part of the study were published in the Lancet Oncology.11

In the dose expansion part of the phase 1 study, [fam-] trastuzumab deruxtecan is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2 positive advanced or metastatic breast cancer and gastric cancer, HER2 low expressing breast cancer and other HER2 expressing solid tumors including colorectal cancer. Overall, 292 patients have been enrolled into this phase 1 study of [fam-] trastuzumab deruxtecan. For more information about the study, visit ClinicalTrials.gov.

About [Fam-] Trastuzumab Deruxtecan
[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia. [Fam-] trastuzumab deruxtecan is in phase 3 development versus ado-trastuzumab emtansine (T-DM1) (DESTINY-Breast03) and versus investigator’s choice post T-DM1 (DESTINY-Breast02) for HER2 positive metastatic breast cancer; pivotal phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01); pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); phase 2 development for HER2 expressing advanced colorectal cancer; phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and, phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer.

[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1, and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan has received SAKIGAKE Designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW).

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

More than 60 Late Breaking Abstracts (LBA’s) are scheduled to be published at this year’s European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (E.S.M.O 2018). Below you will find the 10 published at the sessions on Saturday 20th October, the second day of the conference. For full analysis identifying new technologies, drugs, targets, start-ups etc. we recommend Commercial Interest at E.S.M.O Annual Meeting 2018: Analytical Tool.

• LBA1_PR – IMpassion130: Results from a global, randomised, double-blind, phase 3 study of atezolizumab (atezo) + nab-paclitaxel (nab-P) vs placebo + nab-P in treatment-naive, locally advanced or metastatic triple-negative breast cancer (mTNBC)
• LBA2_PR – Overall survival (OS) with palbociclib plus fulvestrant in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2_) advanced breast cancer (ABC): Analyses from PALOMA-3
• LBA3_PR – Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): results of the Phase 3 SOLAR-1 trial
• LBA11 – Defining the lethal subclone in metastatic lung cancer
• LBA22 – Negative hyper-selection of RAS wild-type (wt) metastatic colorectal cancer (mCRC) patients randomized to first-line FOLFOX plus panitumumab (Pan) followed by maintenance therapy with either 5FU/LV plus Pan or single-agent Pan: translational analyses of the VALENTINO study
• LBA23 – Eltanexor (KPT-8602), a Second-Generation Selective Inhibitor of Nuclear Export (SINE) Compound, in Patients with Metastatic Colorectal Cancer (mCRC)
• LBA31 – Molecular correlates differentiate response to atezolizumab (atezo) + bevacizumab (bev) vs sunitinib (sun): results from a Phase III study (IMmotion151) in untreated metastatic renal cell carcinoma (mRCC)
• LBA32 – Nivolumab (N) Alone or in Combination With Ipilimumab (I) in Patients (pts) With Platinum-Pretreated Metastatic Urothelial Carcinoma (mUC), Including the Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg Expansion From CheckMate 032
• LBA35 – TROPHIMMUN, a 2 cohort phase II trial of the anti-PD-L1 monoclonal antibody avelumab in chemo-resistant gestational trophoblastic neoplasia (GTN) patients: preliminary outcomes in cohort A.
• LBA36 – Association of PD-L1 Expression and Gene Expression Profiling With Clinical Response to Pembrolizumab in Patients With Advanced Recurrent Ovarian Cancer: Results From the Phase 2 KEYNOTE-100 Study

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On October 20, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX) (TASE: BLRX.TA), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported its additional data from the in-depth analyses of biopsies of 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 20, 2018, View Source;p=RssLanding&cat=news&id=2372552 [SID1234530001]). The results presented today at a poster discussion session at the European Society for Medical Oncology 2018 Congress, in Munich, Germany, demonstrate that BL-8040 significantly improves T-cell infiltration into the tumor and reduces immunosuppression in the tumor microenvironment. These data follow top-line results of the COMBAT/KEYNOTE-202 study announced yesterday, October 19, 2018, showing encouraging disease control and extended overall survival, particularly in patients undergoing second-line treatment.

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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 additional data from in-depth analyses of biopsies taken at screening and following monotherapy or combination treatment of BL-8040 and KEYTRUDA demonstrate that in 75% of the available biopsies, BL-8040 treatment promotes an increase in the number of infiltrating CD4+, CD8+ and CD8+Granzyme B+ cytotoxic T-cells. The greatest improvement in T-cell infiltration was observed following combination treatment of BL-8040 and KEYTRUDA and was correlated with stable disease for 8 cycles of treatment. Furthermore, increased infiltration of activated CD4 and CD8 T-cells was accompanied by a pronounced decrease in the number of tumor cells, as well as by a decrease in myeloid-derived suppressor cells, a cell type known to impede the anti-tumor immune response.

Philip Serlin, Chief Executive Officer of BioLineRx, commented. "The data we disclosed today further support BL-8040 as a powerful immune modulating agent, which promotes infiltration of T-cells into the tumor and decreases immuno-suppressive cells in the tumor microenvironment, even more so when combined with KEYTRUDA. This, once again, attests to the potential of the combination treatment as an effective immunotherapy for pancreatic cancer. We look forward to commencing the triple combination arm through the addition of chemotherapy expected 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 20, 2018 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with a pipeline of immune checkpoint antibodies, cancer vaccines, and adoptive cell therapies2, reported its clinical data on its lead CTLA-4 and PD-1 programs today at the 2018 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, in Munich, Germany (Press release, Agenus, OCT 20, 2018, View Source;ctla-4-at-esmo-2018-300734715.html [SID1234530018]).

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"We have initiated expanded clinical trials designed for potential approval of our proprietary PD-1 and CTLA-4 antibodies in second line cervical cancer," said Garo Armen, Ph.D., Chairman and CEO of Agenus. "We are pursuing both monotherapy and combination trials as a dual track regulatory strategy with a planned BLA filing as early as 2020."

Data presented at ESMO (Free ESMO Whitepaper) is based on 76 patients treated with PD-1 (AGEN2034) as well as combination PD-1 and CTLA-4 (AGEN1884) regimens.

Agenus’ anti-PD-1 (AGEN2034) and CTLA-4 (AGEN1884) reveal clinical activity across multiple solid tumors, including breast and gynecologic cancers such as cervical and ovarian.
Patients treated with AGEN2034 reveal a clinical benefit rate of 68% in evaluable patients with metastatic and/or locally advanced solid tumors, and in 3 of 7 evaluable patients with refractory cervical cancer.
Data from combination AGEN2034 plus AGEN1884 show similar trends; early clinical benefit observed in 7 of 16 evaluable patients with ovarian, breast, and soft tissue sarcoma, including a durable response in a patient with ovarian cancer.
Since the ESMO (Free ESMO Whitepaper) data cut-off, early evidence of clinical benefit was observed in patients with cervical cancer treated with combination AGEN2034 and AGEN1884. ESMO (Free ESMO Whitepaper) posters are available at View Source

1Clinical benefit is defined as complete response, partial response and/or disease stabilization
2Through AgenTus Therapeutics, a subsidiary of Agenus