On June 6, 2017 Eleven Biotherapeutics, Inc. (NASDAQ:EBIO), a late-stage clinical oncology company advancing a broad pipeline of novel product candidates based on its Targeted Protein Therapeutics (TPTs) platform, reported the signing of a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) on the development of Eleven’s targeted therapeutic, ViciniumTM in combination with AstraZeneca’s immune checkpoint inhibitor, ImfinziTM (durvalumab), for the treatment of non-muscle invasive bladder cancer (NMIBC) (Press release, Eleven Biotherapeutics, JUN 6, 2017, View Source [SID1234519435]). Schedule your 30 min Free 1stOncology Demo! "Despite current therapies and surgical regimens, there remains a large unmet need for patients with recurring or progressing NMIBC that is no longer responding to Bacillus Calmette-Guérin (BCG)," said Stephen Hurly, President and Chief Executive Officer of Eleven Biotherapeutics. "While we remain internally focused on advancing our Phase 3 registration trial of Vicinium as a monotherapy, preclinical data suggests that Vicinium also has the ability to potentiate the activity of immuno-oncology agents. We are pleased to enter into this collaboration with the National Cancer Institute and AstraZeneca, which broadens the scope of our ongoing clinical program and enables us to evaluate Vicinium together with Imfinzi, a PD-L1 checkpoint inhibitor. We look forward to generating additional data, as we continue to advance Vicinium and work expeditiously to bring it forward as a new treatment option for patients with NMIBC."
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Vicinium, like Eleven’s other TPTs, is a single protein molecule composed of an antibody fragment genetically fused to a potent cytotoxic payload. Vicinium selectively binds to epithelial cell adhesion molecules (EpCAM), a cell surface marker that is highly expressed on many cancers, including high grade NMIBC, but that is present at minimal to no levels on healthy bladder tissue. After binding to EpCAM on the surface of the tumor cell, Vicinium is internalized into the cell where its potent cytotoxic cell killing payload, Pseudomonas Exotoxin A (ETA), is released, disrupting protein synthesis and leading to cell death.
At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2017, new preclinical data were presented demonstrating that cancer cells treated with VB4-845, the active pharmaceutical ingredient used to formulate Vicinium, undergo immunogenic cell death (ICD). ICD is known to stimulate host immune responses against cancer. This supports the hypothesis that Eleven’s TPTs not only directly kill tumor cells, but also induce a host immune cell-mediated anti-tumor response. This suggests that they are differentiated from existing treatments, and that they may have synergy with checkpoint inhibitors and other immuno-oncology compounds.
Under the terms of the CRADA, the NCI, led by principal investigator Dr. Piyush Agarwal of the NCI Center for Cancer Research, Urologic Oncology Branch, will conduct a Phase 1 clinical trial in patients with high-grade NMIBC to evaluate the safety, efficacy, and biological correlates of the Vicinium and durvalumab combination therapeutic strategy. Patients will be evaluated for response and recurrence throughout the study. For referrals, please contact Sonia Bellfield, Research Nurse, at 301-435-6255.
Vicinium is currently in a Phase 3 registration trial for the treatment of high-grade NMIBC. Eleven expects to complete patient enrollment in the second half of 2017, and to report topline 3-month data in the second quarter of 2018. Imfinzi, in development by AstraZeneca and its biologic research arm, MedImmune, is a human monoclonal antibody directed against programmed death ligand-1 (PD-L1), that has accelerated approval by the FDA for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, regardless of PD-L1 status.
About ViciniumTM
Vicinium is a single protein anti-epithelial cell adhesion molecule (anti-EpCAM) fusion protein fused with Pseudomonas Exotoxin A (ETA) designed to specifically target and deliver a potent anti-cancer payload directly into tumor cells. Vicinium is currently in a Phase 3 registration clinical trial for the treatment of high-grade non-muscle invasive bladder cancer (NMIBC) in subjects who have previously received two courses of Bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Eleven Biotherapeutics intends to enroll 134 subjects in the trial, including 77 subjects with carcinoma in situ (CIS), at over 70 centers in the United States and Canada. Primary and secondary endpoints include complete response (CR) rate in CIS subjects, time to disease recurrence and event free survival.
About Imfinzi (durvalumab)
Imfinzi (durvalumab, previously known as MEDI4736) is a human monoclonal antibody directed against PD-L1, which blocks the interaction of PD-L1 with PD-1 and CD80.
Durvalumab is also being tested in the 1st-line treatment of patients with unresectable and metastatic bladder cancer as a monotherapy and in combination with tremelimumab, a checkpoint inhibitor that targets CTLA-4, as part of the DANUBE Phase III trial, which had the last patient commenced dosing during the first quarter of 2017 (global trial, excluding China). Additional clinical trials are ongoing to investigate durvalumab as monotherapy or in combination in multiple solid tumours and blood cancers.
Affimed Presents Data on First-in-Class BCMA-Targeting Immune Cell Engager AFM26 at ASCO Annual Meeting 2017
On June 6, 2017 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, reported that the Company presented data on its preclinical AFM26 program to treat multiple myeloma (MM) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting being held in Chicago, IL, June 2-6, 2017 (Press release, Affimed, JUN 6, 2017, View Source [SID1234519434]). Schedule your 30 min Free 1stOncology Demo! "NK-cells have been described to play a major role in the control of multiple myeloma, however, the recognition and elimination of malignant cells remain challenging," said Dr. Martin Treder, CSO of Affimed. "Our bispecific tetravalent NK-cell engager AFM26, a targeted therapeutic specifically binding BCMA on tumor cells, promises to address this need by unlocking NK-cell cytotoxicity in myeloma."
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Affimed’s first-in-class tetravalent, bispecific antibody AFM26 binds to the tumor-specific B-cell maturation antigen (BCMA) on MM cells and to CD16A on NK-cells, thereby specifically directing NK-cell anti-tumor activity towards cells expressing BCMA.
In a poster presented June 5, 2017, the Company demonstrated that AFM26 induced NK-cellmediated lysis of primary myeloma cells and myeloma cell lines more potently than both daratumumab and elotuzumab, two monoclonal antibodies (mAbs) currently approved for myeloma treatment. AFM26 engages NK-cells with markedly higher avidity compared to classical mAbs. This translates into potent and efficacious target cell lysis and retained activity against cell lines that express very low BCMA levels (BCMA-low). Further differentiating Affimed’s NK-cell engager, the Company presented data showing that AFM26 potently induced lysis of BCMA-low cell lines that have been described as not sensitive to treatment with GSK2857916, a BCMA-targeting antibody drug conjugate currently in clinical development. Importantly, unlike daratumumab and elotuzumab, AFM26 did not elicit NK-cell depletion in vitro.
MM is characterized by high level production of monoclonal immunoglobulin (M-protein), which competes with classical mAbs for NK-cell binding. Affimed demonstrated that both NK-cell binding affinity and cell surface retention of AFM26 were largely unaffected by serum IgG, suggesting retained cytotoxic activity of the NK-cell engager in patients with high M-protein serum levels.
In addition, the Company presented data showing that AFM26, while effectively lysing target cells, elicited substantially lower cytokine release compared to a BCMA/CD3-specific T-cell engager (BiTE), indicating a potentially superior safety profile.
Addressing minimal residual disease (MRD) following high-dose therapy (HDT) and autologous stem cell transplant (ASCT) remains a significant unmet need in MM treatment as the majority of patients relapse. NK-cells are the first lymphocyte population to reappear after HDT/ASCT providing a specific treatment window for NK-cell-based immunotherapeutic approaches to target MRD shortly after transplant. Furthermore, adoptive transfer of NK-cells has recently been clinically investigated in the transplant setting suggesting a unique combination opportunity for AFM26 with this approach.
In summary, the data presented at ASCO (Free ASCO Whitepaper) highlight AFM26 as a promising first-in-class therapeutic with particular potential to address the unmet need in ASCT-eligible MM.
Data of Chugai’s Alecensa® Presented at the American Society of Clinical Oncology on Global Phase III ALEX Study
On June 6, 2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced today that the results of the global phase III study (the ALEX study) of Alecensa, conducted by F. Hoffmann-La Roche Ltd., in ALK fusion gene positive non-small cell lung cancer (NSCLC) patients, will be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) held in Chicago (Press release, Chugai, JUN 6, 2017, View Source [SID1234519433]). The presentation will be held on oral abstract sessions on 6th June (Tue) 12:09-12:21 (CDT) as a late breaking subject. Schedule your 30 min Free 1stOncology Demo! Abstract LBA9008
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Alectinib versus crizotinib in treatment-naive advanced ALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study.
"In the ALEX study comparing the efficacy and safety of first line therapy of Alecensa with crizotinib, Alecensa showed a significant prolongation of PFS and reduced the risk of disease progression or occurrence by 84% in patients with or without brain metastasis at baseline. The study also showed that Alecensa was well tolerated. These results will encourage the patients to fight cancer," said Dr. Yasushi Ito, Senior Vice President, Head of Project & Lifecycle Management Unit. "We believe that Alecensa will also contribute to improving the outcomes of many ALK fusion gene positive NSCLC patients not just in Japan but in overseas as well."
The ALEX study was an open-label, randomized global phase III study that compares the efficacy and safety between Alecensa and crizotinib in the first line therapy. The ALEX study enrolled treatment-naïve 303 patients with ALK fusion gene positive NSCLC. The subjects were allocated to either the Alecensa arm or the crizotinib arm in a one to one ratio. The primary endpoint of the ALEX study was PFS as assessed by the investigator. The secondary endpoints included independent review committee (IRC)-assessed PFS, IRC-assessed time to CNS progression, objective response rate, overall survival, safety and other endpoints.
Summaries of the ALEX study results
Efficacy:
– At the primary data cut-off, Alecensa arm demonstrated statistically significant improvement superiority vs crizotinib arm, reducing risk of progression or death by 53% (HR=0.47, 95%CI: 0.34-0.65, stratified log-rank test, p<0.0001) by investigators’ assessment. Median PFS was not reached (95%CI: 17.7-not reached) in the Alecensa arm while it was 11.1 months (95%CI: 9.1-13.1) in the crizotinib arm.
– According to independent review committee, Alecensa arm demonstrated statistically significant improvement superiority vs crizotinib arm, reducing risk of progression or death by 50% (HR=0.50, 95%CI: 0.36-0.70). Median PFS was 25.7 months (95%CI: 19.9-not reached) in the Alecensa arm while it was 10.4 months (95%CI: 7.7-14.6) in the crizotinib arm.
– Alecensa arm demonstrated improvement vs crizotinib arm, reducing risk of CNS progression or death by 84% (HR=0.16, 95% CI: 0.10-0.28).
– Overall survival data are currently considered immature with only about a quarter of events being reported.
Safety:
– Grade 3-5 adverse events (AEs) were less frequent with Alecensa arm, 41%, vs 50% with crizotinib arm.
– No new safety findings were observed in either arm.
About Alecensa
Alecensa is a highly selective oral ALK inhibitor created by Chugai. It has been reported that approximately five percent of patients with NSCLC express a chromosomal rearrangement which leads to fusion of the ALK gene with another gene.1) ALK kinase signalling is constantly active in cells with such fusion genes, resulting in uncontrolled growth of tumour cells and transforming the cells into tumour cells.2, 3) Alecensa exerts its anti-tumour effect by selectively inhibiting ALK kinase activity to inhibit tumour cell proliferation and induce cell death.4) In addition, Alecensa is not recognized by the active efflux system in the blood brain barrier which actively pumps molecules out of the brain. Thus, Alecensa is able to remain active in the central nervous system and has proven activity against brain metastases.
Alecensa is currently approved in the United States, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, the EU, Australia, Taiwan and Singapore for the treatment of adult patients with ALK-positive, metastatic (advanced) NSCLC who have progressed on or those intolerant to crizotinib." In Japan, "Alecensa capsule 150mg" is available to patients with "ALK fusion gene positive unresectable, recurrent/advanced NSCLC" and is marketed by Chugai.
The approved dosage and administration in Japan is "300mg alectinib is administered orally twice daily for adult patient."
1) Biomarker committee of The Japan Lung Cancer Society, Guidelines for ALK gene tests in lung cancer patients
2) Soda et al., Nature. 448: 561-566 (2007)
3) Takeuchi et al., Clin Cancer Res. 15: 3143-3149 (2009)
4) Sakamoto et al., Cancer Cell. 19: 679-690 (2011)
Intellia Therapeutics and San Raffaele University and Research Hospital to Combine CRISPR/Cas9 Genome Editing with Enhanced Cell Therapies to Fight Cancer
On June 6, 2017 Intellia Therapeutics (NASDAQ:NTLA), a leading genome editing company, and San Raffaele University and Research Hospital, a leading scientific institution, reported that they have entered into a three-year research collaboration, option and license agreement to engineer optimized T cell cancer therapies (Press release, Intellia Therapeutics, JUN 6, 2017, View Source [SID1234519419]). The goal of the collaboration is to discover innovative tools to target tough-to-treat cancers, while leveraging Intellia’s proprietary CRISPR/Cas9 platform to generate next-generation T cell therapies that will address unmet needs in both hematological and solid tumors. Professor Chiara Bonini, Head of San Raffaele’s Experimental Hematology Unit and Deputy Director of the Division of Immunology, Transplantation and Infectious Diseases, will lead the scientific work at San Raffaele. Schedule your 30 min Free 1stOncology Demo! The collaboration marks the first external partnership of Intellia’s eXtellia division. eXtellia’s long-term strategy is focused on advancing new generations of engineered cell therapies through the unique and proprietary applications of CRISPR genome editing. eXtellia was established in 2016, and has identified its initial areas of focus as immuno-oncology and auto-immunity, where genome-edited cell therapy offers a potentially powerful and differentiated therapeutic modality. The agreement also includes options and licenses to key technologies for production of engineered cell therapies developed at San Raffaele.
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"Through this collaboration, eXtellia aims to apply CRISPR/Cas9 genome editing in a multi-faceted way to modulate the fundamental properties of engineered immune cells and amplify their anti-cancer properties far beyond current applications," said Andrew Schiermeier, Ph.D., Senior Vice President, eXtellia. "San Raffaele and Dr. Bonini are recognized globally as leaders in cell therapy and immuno-oncology, with excellent track records in translating innovative research into approved therapies. We aspire to one day cure cancer in patients who are fighting every day with few or no treatment options."
"T cell therapy has recently produced impressive results in clinical trials in specific cancer types. However, to realize the full potential of T cell therapy, including in a broader set of cancer types, next generation cellular products are needed," said Professor Chiara Bonini. "Intellia’s leadership in genome editing will be critical to achieve this goal and shape this new class of ‘living drugs’."
Data of Chugai’s Alecensa Presented at the American Society of Clinical Oncology on Global Phase III ALEX Study – Alecensa Demonstrates Statistically Significant Improvement PFS and Reducing Risk of CNS Progression or Death –
On June 6, 2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the results of the global phase III study (the ALEX study) of Alecensa, conducted by F. Hoffmann-La Roche Ltd., in ALK fusion gene positive non-small cell lung cancer (NSCLC) patients, will be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) held in Chicago (Press release, Chugai, JUN 6, 2017, View Source [SID1234519410]). The presentation will be held on oral abstract sessions on 6th June (Tue) 12:09-12:21 (CDT) as a late breaking subject. Schedule your 30 min Free 1stOncology Demo! Abstract LBA9008
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Alectinib versus crizotinib in treatment-naive advanced ALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study.
"In the ALEX study comparing the efficacy and safety of first line therapy of Alecensa with crizotinib, Alecensa showed a significant prolongation of PFS and reduced the risk of disease progression by 84% in patients with brain metastasis. The study also showed that Alecensa was well tolerated. These results will encourage the patients to fight cancer," said Dr. Yasushi Ito, Senior Vice President, Head of Project & Lifecycle Management Unit. "We believe that Alecensa will also contribute to improving the outcomes of many ALK fusion gene positive NSCLC patients not just in Japanese but overseas."
The ALEX study was an open-label, randomized global phase III study that compares the efficacy and safety between Alecensa and crizotinib in the first line therapy. The ALEX study enrolled treatment-naïve 303 patients with ALK fusion gene positive NSCLC. The subjects were allocated to either the Alecensa arm or the crizotinib arm in a one to one ratio. The primary endpoint of the ALEX study was PFS as assessed by the investigator. The secondary endpoints included independent review committee (IRC)-assessed PFS, IRC-assessed time to CNS progression, objective response rate, overall survival, safety and other endpoints.
Summaries of the ALEX study results
Efficacy:
– At the primary data cut-off, Alecensa arm demonstrated statistically significant improvement superiority vs crizotinib arm, reducing risk of progression or death by 53% (HR=0.47, 95%CI: 0.34-0.65, stratified log-rank test, p<0.0001) by investigators’ assessment. Median PFS was not reached (95%CI: 17.7-not reached) in the Alecensa arm while it was 11.1 months (95%CI: 9.1-13.1) in the crizotinib arm.
– According to independent review committee, Alecensa arm demonstrated statistically significant improvement superiority vs crizotinib arm, reducing risk of progression or death by 50% (HR=0.50, 95%CI: 0.36-0.70). Median PFS was 25.7 months (95%CI: 19.9-not reached) in the Alecensa arm while it was 10.4 months (95%CI: 7.7-14.6) in the crizotinib arm.
– Alecensa arm demonstrated improvement vs crizotinib arm, reducing risk of CNS progression or death by 84% (HR=0.16, 95% CI: 0.10-0.28).
– Overall survival data are currently considered immature with only about a quarter of events being reported.
Safety:
– Grade 3-5 adverse events (AEs) were less frequent with Alecensa arm, 41%, vs 50% with crizotinib arm.
– No new safety findings were observed in either arm.
About Alecensa
Alecensa is a highly selective oral ALK inhibitor created by Chugai. It has been reported that approximately five percent of patients with NSCLC express a chromosomal rearrangement which leads to fusion of the ALK gene with another gene.1) ALK kinase signalling is constantly active in cells with such fusion genes, resulting in uncontrolled growth of tumour cells and transforming the cells into tumour cells.2, 3) Alecensa exerts its anti-tumour effect by selectively inhibiting ALK kinase activity to inhibit tumour cell proliferation and induce cell death.4) In addition, Alecensa is not recognized by the active efflux system in the blood brain barrier which actively pumps molecules out of the brain. Thus, Alecensa is able to remain active in the central nervous system and has proven activity against brain metastases.
Alecensa is currently approved in the United States, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, the EU, Australia, Taiwan and Singapore for the treatment of adult patients with ALK-positive, metastatic (advanced) NSCLC who have progressed on or those intolerant to crizotinib." In Japan, "Alecensa capsule 150mg" is available to patients with "ALK fusion gene positive unresectable, recurrent/advanced NSCLC" and is marketed by Chugai.
The approved dosage and administration in Japan is "300mg alectinib is administered orally twice daily for adult patient."
1) Biomarker committee of The Japan Lung Cancer Society, Guidelines for ALK gene tests in lung cancer patients
2) Soda et al., Nature. 448: 561-566 (2007)
3) Takeuchi et al., Clin Cancer Res. 15: 3143-3149 (2009)
4) Sakamoto et al., Cancer Cell. 19: 679-690 (2011)