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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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
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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)
Final results of the MIN-001-1203 study with 2OHOA in oncology presented at ASCO 2017 annual meeting in Chicago
On June 5, 2017 Laminar Pharma, a pioneering clinical stage biopharmaceutical company developing a new generation of products modulating metabolism of membrane lipids based on the groundbreaking MLT platform, reported that the final results of the of MIN-001-1203 clinical study with 2OHOA in patients with advanced solid tumours, including malignant glioma, have been presented at a poster session within the Developmental Therapeutics and Translational Research track at the 2017 ASCO (Free ASCO Whitepaper) meeting in Chicago (Press release, Laminar Pharma, JUN 5, 2017, View Source [SID1234562097]). 5 leading clinical investigational sites in Spain and in the UK have participated in this study.
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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
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2OHOA, administered as an oral suspension two (BID) or three (TID) times daily, has been generally well tolerated in monotherapy up to 12 g/day, while patients have had difficulties to handle the large volume of liquid intake required for 16g/day (8 g BID), experiencing frequent gastrointestinal effects. Overall 54 patients have received 2OHOA at different doses. One Dose Limiting Toxicity (DLT) was reported at the dose of 12g/day and 3 DLT at 16g/day. 12G/day (4g TID) was confirmed as the maximum Tolerated Dose (MTD) since there were no DLTs reported in the second part of the study conducted with this dose (expansion phase)
No drug-related serious adverse events or other relevant toxicity effects associated to the investigational product have been reported in any of the 54 patients treated, other than the tolerability issues experienced at the highest dose levels (gastrointestinal effects). Study drug related AE (≥10%) at any grade were diarrhoea (53 [26%]), vomiting (29[14%]), nausea (26 [13%]). No G3/G4 whether regardless of study drug relationship or suspected as being study drug related occurred over 10% of patients.
Pharmacokinetic (PK) profile was determined. 2OHOA was quantifiable in all dose levels and maximum concentration (Cmax) was reached at 1 hour after administration in the fasted state. When administered under fed conditions, 2OHOA had bioavailability comparable to that found in the fasted state, although food caused a non-clinically significant delay in the time needed to reach the CMax. Therefore, 2OHOA could be taken without regard to food. The half-life was between 1.4 and 4.6 hours up to 8g/day, increasing to more than 7h at the higher doses. Systemic exposure of 2OHOA increased in proportion to dose following single and repeat BID administration. After repeat BID dosing, systemic exposure of 2OHOA, increased between 1- and 1.7-fold from first dose on Day 1 to last dose on Day 21. PK data supports the planned twice-a-day oral administration of 2OHOA
Very encouraging anti-cancer activity of 2OHOA as single agent has been confirmed in several recurrent, heavily pre-treated patients, including 5 recurrent High Grade Glioma (rHGG) and 3 with other advanced solid tumours (AST). One recurrent glioblastoma (rGBM) pt had sustained partial response for more than 2.5 years (93% shrinkage of target lesion) and 4 rHGG patients (3 GBM) achieved stable disease (SD), by RANO, for at least 6 months. Other 3 AST patients had clinical benefit by RECIST: 1 with mesothelioma (SD for 10 months), 1 with colorectal cancer (SD for 3 months) and 1 with lung metastasis of biliary duct carcinoma (SD for 5 months)
Preliminary analysis of available biomarkers data confirms biological activity by 2OHOA in cancer patients. On the one hand, a reduction of GFAP levels in plasma from rHGG patients after 8 days of treatment was observed in more than 80% of patients analyzed. Average reduction in GFAP levels in the whole set of patients was 20% (n=15). On the other hand, initial analysis of plasma miRNA expression profiles in a subset of 22 patients, shows that at least 3 miRNA were differentially expressed in response to 2OHOA treatment. Target gene analysis of these miRNA is ongoing. These, and other potential plasmatic biomarkers currently being analyzed, are expected to be developed and eventually validated in future clinical studies with 2OHOA, providing valuable support for patient selection strategies and for clinical study design.
Further clinical studies with 2OHOA are currently under preparation, including a Phase IIb study to evaluate the potential clinical benefit of adding 2OHOA to the current Standard of Care (SoC) in patients with newly-diagnosed glioblastoma, given that "the preliminary antitumor activity including a sustained PR in heavy pretreated rHGG pt warrants further investigation in a Ph2 study", as concluded in the poster presented by Dr. A. Azaro, Principal investigator at Vall d’Hebron Institute of Oncology (VHIO), one of the 5 sites participating in this study, and the first author of the poster presented at ASCO (Free ASCO Whitepaper).
Laminar Pharma is also preparing a PI trial in children with malignant glioma and other advanced cancers is being prepared in the USA, with the collaboration of top clinical investigational institutions in New Jersey and Boston.