On October 21, 2018 Leap Therapeutics, Inc. (NASDAQ: LPTX) reported its clinical data from its ongoing Phase I/II study of DKN-01 in combination with Keytruda (pembrolizumab) in patients with advanced esophagogastric cancer at the European Society for Molecular Oncology (ESMO) (Free ESMO Whitepaper) 2018 Annual Congress (Press release, Leap Therapeutics, OCT 21, 2018, View Source [SID1234530017]).

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Leap will host a live conference call and webcast on Monday, October 22 at 8:00 AM US Eastern Time / 2:00 PM Central European Time, with Samuel Klempner, MD, Director, Precision Medicine Program, The Angeles Clinic and Research Institute, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center. Dr. Klempner will describe his experience with patients in the study.

Clinical Data Presented at ESMO (Free ESMO Whitepaper)

Midway through the study, the combination of DKN-01 and pembrolizumab has demonstrated promising clinical activity with a 23.5% overall response rate and 58.8% disease control rate in evaluable gastric or gastroesophageal junction cancer patients who have been heavily pretreated and have not had prior anti-PD-1/PD-L1 therapy (PD-1/PD-L1 naïve). The combination has generated durable responses in subgroups less likely to respond to pembrolizumab monotherapy, for example, patients whose tumors are microsatellite stable (MSS) and/or PD-L1 negative. The combination of DKN-01 and pembrolizumab may have additive clinical benefit through the targeting of both innate and adaptive immunity. Data to date suggest that elevated tumor expression of DKK1 may correlate with better patient outcomes. Biomarker analyses are underway to guide future clinical development in gastroesophageal malignancies.

Esophagogastric Cancer Clinical Trial (P102)

The esophagogastric cancer clinical trial (P102) is a multipart study of DKN-01 as a monotherapy and in combination with paclitaxel or pembrolizumab. The arm evaluating DKN- 01 plus pembrolizumab includes both dose escalation and dose confirmation cohorts and is designed to assess the safety, pharmacokinetics and efficacy of the combination. Data from the monotherapy and paclitaxel arms of the study have been presented previously and will be updated later in the year.

As of the September 26, 2018 cut-off date for the presentation, forty-five patients have been enrolled in the DKN-01 plus pembrolizumab study, thirty-eight PD-1/PD-L1 naïve and seven refractory to PD-1/PD-L1 therapy. Two of the patients were enrolled in the 150mg DKN-01 dose, and forty-three patients at the 300mg DKN-01 dose. Leap expects that the PD-1/PD-L1 naïve group will complete enrollment before the end of 2018.

DKN-01 plus Keytruda
Clinical Results as of September 26, 2018

300mg DKN-01
Anti-PD1/PD-L1 Naïve

Patients

Response Rate

Disease
Control
Rate

Partial Response

Stable Disease

Progressive Disease

All responding patients in the study had MSS tumors. The overall response rate for Keytruda monotherapy in gastric or gastroesophageal junction patients with non-microsatellite instability high tumors in the KN-059 (n = 167) and KN-061 (n = 281) studies was 9.0% and 9.3%, respectively.

When this study is complete, Leap expects to choose an indication for a larger, controlled clinical study.

DKN-01 Clinical Perspectives Conference Call and Webcast:

On Monday, October 22, 2018 at 8:00AM ET/2:00PM CET, Leap will be hosting a conference call and webcast for the investment community. To access the conference call, please dial (866) 589-0108 (US/Canada Toll-Free) or (409) 231-2048 (international) and refer to conference ID 1249999. The presentation will also be webcast live and will be available under "Events & Presentations" in the Investor section of Leap’s website, View Source A replay of the webcast will be available on Leap’s website approximately two hours after the event and will be available for a limited time.

On October 21, 2018 FUJIFILM Medical Systems U.S.A., Inc., a leading provider of diagnostic imaging and medical informatics solutions, today introduced the FCT Embrace (Press release, Fujifilm, OCT 21, 2018, View Source [SID1234530089]). Powered by Analogic, the FCT Embrace is the world’s first 85cm wide bore computed tomography (CT) imaging unit with 64 or 128 slice configurations. Optimized for both oncology and radiology applications, the FCT Embrace, combined with other market-leading oncology solutions, offers enhanced and efficient CT Simulation with radiotherapy treatment planning capabilities. The unveiling at booth #3063 during the 2018 American Society for Radiation Oncology (ASTRO) Annual Meeting marks Fujifilm’s entry into the CT market, expanding its end-to-end diagnostic imaging product portfolio which is recognized for exceptional imaging at low dose.

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"Fujifilm is a company of ‘firsts’ in diagnostic imaging. In 1936, we took our first steps in the development of X-ray film; and in 1983, we pioneered the first digitized radiography system in the world," said Johann Fernando, Ph.D., Chief Operating Officer of FUJIFILM Medical Systems U.S.A., Inc. "Once again we are innovating with the launch of the FCT Embrace, a solution that provides the most slices ever seen on an 85cm bore system. Designed to improve radiation oncology care, this advanced solution boosts patient comfort and security by offering the widest tabletop currently available at 49cm, and accommodating bariatric patients of up to 660lbs."

The new, state-of-the-art FCT Embrace provides exceptional imaging capabilities on an easy-to-use, standardized platform for both radiology and oncology. Designed to improve accuracy throughout the entire oncology care cycle, the 85cm bore optimally matches the rotational arc of the linear accelerator—offering easy and precise positioning options for simulation and treatment planning. This unique solution allows oncology patients to be imaged in their optimal treatment position at the full clinical image quality afforded by 64 slice or greater systems for the first time; maintaining the accuracy requirements radiation oncology demands without compromising diagnostic image quality.

With over 80 years of medical imaging experience, Fujifilm’s expertise in brilliant image quality, low dose, and patient comfort is now available to the CT market for oncology, interventional CT and radiology.

For more information on Fujifilm’s solutions, please visit: www.fujimed.com.

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