- |||||||||| Avastin (bevacizumab) / Roche, Opdivo (nivolumab) / Ono Pharma, BMS
[VIRTUAL] Venous thromboembolism (VTE) incidence and risk factors in patients (pts) with non-small cell lung cancer (NSCLC) receiving front-line therapy. () - Apr 29, 2020 - Abstract #ASCO2020ASCO_5002; Khorana risk score was significantly associated with VTE risk and may identify those likely to benefit from thromboprophylaxis. *HR: hazard ratio †Comorbidities included diabetes, central venous catheter, pacemaker, heart failure, atrial fibrillation, liver disease, kidney disease, nicotine dependence, prior VTE.
- |||||||||| [VIRTUAL] Trends in ALK inhibitors for non-small cell lung cancer. () - Apr 29, 2020 - Abstract #ASCO2020ASCO_3210;
Furthermore, the increased ER and in-patient costs may substantiate the findings of the ALEX trial, notably higher liver toxicity and more nausea, vomiting, and diarrhea for crizotinib. There is not yet sufficient data on the newer ALK inhibitors, brigatinib and lorlatinib in the real-world.
- |||||||||| Zykadia (ceritinib) / Novartis
Preclinical, Journal, Myeloid-derived suppressor cells: LDK378 inhibits the recruitment of myeloid derived suppressor cells to spleen via the p38/GRK2/CCR2 pathway in mice with sepsis. (Pubmed Central) - Apr 26, 2020 Furthermore, in vitro experiments also showed that lipopolysaccharide (LPS)-induced migration of MDSCs was similarly owing to the activation of GRK2 and up-regulation of CCR2 by LPS, whereas the treatment with LDK378 partially blocked the LPS-induced phosphorylation of p38 and GRK2 and decreased the expression of CCR2 on the cell surface, therefore leading to the suppression of MDSC migration. Together, these findings unravel a novel function of LDK378 in the host response to infection and suggest that LDK378 could be a potential therapeutic agent for sepsis.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Retrospective data, Journal: Comparative Efficacy of Targeted Therapies in Patients with Non-Small Cell Lung Cancer: A Network Meta-Analysis of Clinical Trials. (Pubmed Central) - Apr 15, 2020 Compared with chemotherapy, both ORR and PFS were significantly improved for afatinib, alectinib, and crizotinib, while only PFS was significantly improved for cabozantinib, ceritinib, gefitinib, and osimertinib...Cabozantinib and alectinib showed the highest probability for the first-line treatment ranking in ORR (62.5%) and PFS (87.5%), respectively. The current network meta-analysis showed the comprehensive evidence-based comparative efficacy of different types of targeted therapies, which would help clinicians use targeted therapies in clinical practice.
- |||||||||| Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene
Phase classification: Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma (clinicaltrials.gov) - Apr 8, 2020 P1, N=27, Suspended, The patients from Japanese cohorts had a higher incidence of ALK-inhibitor pneumonitis, which indicates the need for increased awareness and caution for pneumonitis in Japanese patients treated with ALK inhibitors. Phase classification: P2 --> P1
- |||||||||| Zykadia (ceritinib) / Novartis, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen, Sprycel (dasatinib) / BMS, Otsuka, Inhibikase
Clinical, Journal: Safety and Activity of the Combination of Ceritinib and Dasatinib in Osteosarcoma. (Pubmed Central) - Apr 1, 2020 The ceritinib/dasatinib combination was applied to the primary cells of a 16-year-old girl with a long history of lung metastases, and was more effective than cabozantinib and olaparib...After the cessation of the therapy, radiological analysis indicated a massive growth of the patient's liver metastases. In conclusion, these data indicate that the combination of ceritinib/dasatinib is safe and may be used to develop new therapy protocols.
- |||||||||| Zykadia (ceritinib) / Novartis
Clinical, Journal, Combination therapy: Interpretation of ceritinib clinical trial results and future combination therapy strategies for ALK-rearranged NSCLC. (Pubmed Central) - Mar 22, 2020 The ALK gene is rearranged in 3-7% of NSCLCs, and targeted inhibition of ALK is a viable therapy option.Areas covered: We discuss the available treatment options for ALK-positive NSCLC with an emphasis on the second-generation ALK inhibitor ceritinib. We also discuss practical treatment strategies and possible strategies to overcome or delay resistance to ALK inhibitors.Expert opinion: With a robust treatment armamentarium for patients with ALK-positive NSCLC, emphasis has shifted to optimizing individualized treatment strategies to further enhance outcomes for these patients.
- |||||||||| Zykadia (ceritinib) / Novartis, pictilisib (GDC-0941) / Roche
Journal: Codrug Approach for the Potential Treatment of EML4-ALK Positive Lung Cancer. (Pubmed Central) - Mar 19, 2020 We have joined the two drugs through a new, pH-sensitive linker where the resulting codrugs are hydrolytically stable at lower pH (pH 6.4) but rapidly cleaved at higher pH (pH 7.4). Compound (19), which was designed for optimal lung retention, demonstrated clean liberation of the drug payloads in vitro and represents a novel approach to targeted lung delivery.
- |||||||||| Zykadia (ceritinib) / Novartis, AZD1208 / AstraZeneca, Alunbrig (brigatinib) / Takeda
Journal: The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status. (Pubmed Central) - Mar 3, 2020 Knockdown of PIM1 sensitizes cells of differing MYCN status to ALK inhibitors, and in patient-derived xenografts of high-risk NB harboring ALK mutations, the combination of the ALK inhibitor ceritinib and PIM1 inhibitor AZD1208 shows significantly enhanced anti-tumor efficacy relative to single agents. These data confirm that PIM1 overexpression decreases sensitivity to ALK inhibitors in NB, and suggests that combined front-line inhibition of ALK and PIM1 is a viable strategy for the treatment of ALK-positive NB independent of MYCN status.
- |||||||||| Zykadia (ceritinib) / Novartis
Biomarker, Journal: IRS2 Amplification as a Predictive Biomarker in Response to Ceritinib in Small Cell Lung Cancer. (Pubmed Central) - Feb 27, 2020 In this study, we present that IRS2 amplification and/or expression serve as preclinical implications for a novel therapeutic target in SCLC progression. Furthermore, we suggest that insulin-like growth factor-1 (IGF-1) receptor inhibitor-based therapy could be used for treating SCLC with IRS2 amplification.
- |||||||||| Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis
Journal: Structural basis for drug resistance mechanisms against anaplastic lymphoma kinase. (Pubmed Central) - Feb 26, 2020 This study will be beneficial for designing drugs with better proficiency against ALK and the issues of drug resistance. This study can be taken as a pipeline for investigating drug-resistant mutations in other diseases as well.
- |||||||||| Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis
Ceritinib +/- Trametinib (STARLIGHT BALLROOM) - Feb 21, 2020 - Abstract #IASLCLCTT2020IASLC_LCTT_236;
- |||||||||| Lorbrena (lorlatinib) / Pfizer
Clinical, Journal: Sarcoid-like reaction mimicking disease progression in an ALK-positive lung cancer patient receiving lorlatinib. (Pubmed Central) - Feb 7, 2020 This invasive approach, besides documenting for the first time a sarcoid-like reaction to ALK inhibitors, allowed to revert the radiological diagnosis and maintain lorlatinib, for the best patient outcome. The pragmatic relevance of these findings suggests a careful attitude towards the interpretation of radiologic patterns of disease progression in patients under TKI.
- |||||||||| Zykadia (ceritinib) / Novartis, Kisqali (ribociclib) / Novartis
Trial primary completion date: NEPENTHE: Next Generation Personalized Neuroblastoma Therapy (clinicaltrials.gov) - Jan 30, 2020 P1, N=131, Recruiting, Active, not recruiting --> Completed Trial primary completion date: Jul 2020 --> Jul 2021
- |||||||||| Piqray (alpelisib) / Novartis, Zykadia (ceritinib) / Novartis, Tabrecta (capmatinib) / Incyte, Novartis
Trial completion, Metastases: A Phase II, Open Label, Multiple Arm Study of AUY922, BYL719, INC280, LDK378 and MEK162 in Chinese Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - Jan 21, 2020 P2, N=66, Completed, Trial completion date: Nov 2021 --> Jul 2022 Recruiting --> Completed
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