- |||||||||| Zykadia (ceritinib) / Novartis
Trial termination, Metastases: Ceritinib Rare Indications Study in ALK+ Tumors (clinicaltrials.gov) - Dec 26, 2019 P2, N=22, Terminated, These findings indicate that HDAC inhibitor pre-treatment followed by a new ALK inhibitors may be useful to circumvent resistance constituted by coexistence of resistance mutations and EMT in the heterogeneous tumor. Completed --> Terminated
- |||||||||| Review, Journal: New generation anaplastic lymphoma kinase inhibitors. (Pubmed Central) - Dec 22, 2019
Some of them were approved after the failure of crizotinib (ceritinib, alectinib, brigatinib and lorlatinib) and in first line setting (ceritinib, alectinib and brigatinib) while others are still under evaluation for TKI-naive patients such as lorlatinib, ensartinib and entrectinib. In this review we will discuss the most recent results of new TKIs in order to describe a fast growing therapeutic landscape in this setting.
- |||||||||| Clinical, Journal: IGF1R Is a Potential New Therapeutic Target for HGNET-BCOR Brain Tumor Patients. (Pubmed Central) - Dec 20, 2019
Ceritinib was able to abrogate the proliferation of PhKh1 cells and blocked the phosphorylation of IGF1R and AKT. (4) IGF1R is as an attractive target for the development of new therapy protocols for HGNET-BCOR patients, which may include ceritinib and vinblastine.
- |||||||||| Zykadia (ceritinib) / Novartis, Focus V (anlotinib) / Advenchen, Sino Biopharmaceutical, Imbruvica (ibrutinib) / AbbVie, J&J
PK/PD data, Preclinical, Journal: A selective and robust UPLC-MS/MS method for the simultaneous quantitative determination of anlotinib, ceritinib and ibrutinib in rat plasma and its application to a pharmacokinetic study. (Pubmed Central) - Dec 19, 2019 ANL, CER and IBR were sufficiently stable under most investigated conditions. The optimized method was successfully applied for a pharmacokinetic study after single oral gavage administration of mixture (ANL, CER and IBR) at dose of 6 mg kg-1, 25 mg kg-1 and 10 mg kg-1.
- |||||||||| Alunbrig (brigatinib) / Takeda
Journal: An evaluation of brigatinib as a promising treatment option for non-small cell lung cancer. (Pubmed Central) - Nov 27, 2019 Besides this TKI, the second-line ALK inhibitors alectinib and ceritinib, as well as the third-line lorlatinib are approved for the treatment of ALK-positive NSCLC patients. The main challenge is to find sequences and combinations of ALK inhibitors which provide the best benefit for the patients.
- |||||||||| Review, Journal: Targeted therapies for ROS1-rearranged non-small cell lung cancer. (Pubmed Central) - Nov 27, 2019
Additionally, appreciation of novel resistance mechanisms to crizotinib has led to the development of newer tyrosine kinase inhibitors (TKIs). In this review, we highlight known and emerging TKIs for the management of ROS1+ NSCLC.
- |||||||||| Zykadia (ceritinib) / Novartis
Journal: HFIP Promoted Low Temperature SNAr of ChloroHeteroarenes Using Thiols and Amines. (Pubmed Central) - Nov 20, 2019 A highly efficient and an unprecedented HFIP promoted low temperature aromatic nucleophilic substitutions of chlorohete-roarenes has been performed using thiols and (secondary) amines under base-free and metal-free conditions. The developed protocol also provides excellent regio-control for the selective functionalisation of dichloroheteroarenes, while the utility of the protocol was demonstrated by the modification of a commercially available drug Ceritinib.
- |||||||||| Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene
Trial completion date, Trial primary completion date, Metastases: Ceritinib + Trametinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - Nov 15, 2019 P1/2, N=69, Recruiting, Trial completion date: Jun 2020 --> Jun 2021 | Trial primary completion date: Jun 2020 --> Jun 2021 Trial completion date: Mar 2021 --> Jun 2021 | Trial primary completion date: Mar 2020 --> Jun 2020
- |||||||||| Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene
Trial suspension: Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma (clinicaltrials.gov) - Nov 13, 2019 P2, N=27, Suspended, Trial completion date: Mar 2021 --> Jun 2021 | Trial primary completion date: Mar 2020 --> Jun 2020 Recruiting --> Suspended
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis
Journal: Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma. (Pubmed Central) - Nov 11, 2019 Furthermore, siRNA-mediated depletion of ALK or IRS2 decreased the phosphorylation of the survival-promoting kinase Akt and of a downstream target, the transcription factor FoxO3, and reduced the viability of three ALK-driven neuroblastoma cell lines. Collectively, our IPP analysis provides insight into the proximal architecture of oncogenic ALK signaling by revealing IRS2 as an adaptor protein that links ALK to neuroblastoma cell survival through the Akt-FoxO3 signaling axis.
- |||||||||| Enrollment open, Trial completion date, Trial initiation date, Trial primary completion date, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker, Metastases: MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) - Nov 5, 2019
P3, N=960, Recruiting, The Jab1/CSN5-mediated stabilization of PD-L1 can be efficiently inhibited by Ceritinib in preclinical animal models of ALK+ ALCL. Not yet recruiting --> Recruiting | Trial completion date: Mar 2024 --> Oct 2024 | Initiation date: Mar 2019 --> Oct 2019 | Trial primary completion date: Mar 2022 --> Oct 2022
- |||||||||| Zykadia (ceritinib) / Novartis
Clinical, Journal: Enteral administration of TKIs: report of a response to ceritinib in an ALK-positive NSCLC patient and literature review. (Pubmed Central) - Oct 31, 2019 In our case, the cerebral and extra-cranial response obtained with enteral ceritinib intake suggests the proposition of novel inhibitors in these circumstances may take place after first-generation compounds failure or even upfront. Indeed, their grater potency and activity against brain metastases point out the role of their enteral administration in the first-line setting too, when a rapid systemic and intra-cerebral disease response is required.
- |||||||||| Zykadia (ceritinib) / Novartis
Phase 0 Trial of Ceritinib in Brain Metastases and Recurrent Glioblastoma (Ballroom Lawn) - Oct 29, 2019 - Abstract #SNO2019SNO_329; Unbound drug concentrations in brain metastasis and glioblastoma appear insufficient for target modulation. Despite recent reports of clinical response, our findings suggest no role for ceritinib in treating glioblastoma and an unfavorable profile for brain metastases.
- |||||||||| Clinical, Review, Journal: ALK inhibitors, resistance development, clinical trials. (Pubmed Central) - Oct 18, 2019
The inevitable emergence of resistance to alk-directed therapy is central to ongoing research and daily clinical practice for affected patients. In the present review, we highlight the current treatment landscape, the available and emerging clinical trials, and the evolving clinical decision-making in ALK-positive nsclc, with a focus on Canadian practice.
- |||||||||| Zykadia (ceritinib) / Novartis, Adcetris (brentuximab vedotin) / Takeda, Pfizer
Enrollment change, Trial withdrawal: Ceritinib With Brentuximab Vedotin in Treating Patients With ALK-Positive Anaplastic Large Cell Lymphoma (clinicaltrials.gov) - Oct 10, 2019 P1/2, N=0, Withdrawn, Here, we review the role of ALK as a therapeutic target in NSCLC, the testing methods for identifying ALK-rearranged NSCLC, and the various TKIs currently being used or explored for treatment in this setting, with a focus on alectinib from a Chinese perspective. N=30 --> 0 | Recruiting --> Withdrawn
- |||||||||| A rare case of large cell neuroendocrine bronchial carcinoma with therapeutic response to ALK inhibitors (A6) - Sep 30, 2019 - Abstract #DGHO2019DGHO_1141;
However, TKI sensitivity was generally lower and the disease course more aggressive, including atypical metastatic sites, than in case of ALK + lung adenocarcinoma, despite presence of the relatively favourable EML4-ALK V2 and wild-type TP53. Moreover, TKI efficacy did not correlate with detection of ALK mutations, since second-line alectinib showed the longest duration of response despite unremarkable ALK sequencing results, while later TKI lines did not confer clinical benefit, despite presence of putatively sensitive ALK mutations based on in vitro results.
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