- |||||||||| Xalkori (crizotinib) / Pfizer, Cabometyx (cabozantinib tablet) / Exelixis, Orpathys (savolitinib) / AstraZeneca, Hutchmed
P2 data, Journal, Metastases: Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma. (Pubmed Central) - Nov 16, 2024 P2 In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease.
- |||||||||| Xalkori (crizotinib) / Pfizer, Rozlytrek (entrectinib) / Roche, Augtyro (repotrectinib) / BMS
Journal: Advances and future directions in ROS1 fusion-positive lung cancer. (Pubmed Central) - Nov 13, 2024 Herein, we describe a practical approach for the selection of initial and subsequent therapies for metastatic ROS1+ NSCLC based on these clinical considerations. Additionally, we explore the evolving evidence for the optimal treatment of earlier-stage, non-metastatic ROS1+ NSCLC, while, in parallel, highlighting future research directions with the goal of continuing to build on the tremendous progress in the management of ROS1+ NSCLC and ultimately improving the longevity and well-being of people living with this disease.
- |||||||||| darovasertib (IDE196) / Ideaya Biosci
Trial completion date, Trial primary completion date: MUM: Study of IDE196 in Patients with Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions (clinicaltrials.gov) - Nov 13, 2024 P1/2, N=341, Recruiting, MD simulation of the complexes revealed that MAC is more stable and exhibits more favourable hydrogen bonding with the ALK receptor's active site than Crizotinib.Communicated by Ramaswamy H. Sarma. Trial completion date: May 2025 --> Mar 2027 | Trial primary completion date: Oct 2024 --> Dec 2026
- |||||||||| Xalkori (crizotinib) / Pfizer
Differential Requirements for the RON Ligand Binding and Kinase Domains in Myeloproliferative Neoplasms (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_5874; Consistent with these results, pharmacological inhibition of RON with the MET/RON inhibitor crizotinib significantly decreased disease burden in MPLW515L mice...This work highlights an important role for RON activity in MPN disease progression, which appears to be specifically related to ligand-independent signaling in the setting of PMF driven by MPLW515L. The promising survival benefits and minimal hematopoietic toxicity associated with genetic inactivation of RON kinase activity in vivo support further investigation of RON inhibitors in PMF.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis
The TFG-ROS1 Fusion Is an Oncogenic Driver of Human Myeloid Leukemia (Room 6A (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_2220; He failed to respond to induction chemotherapy based on Cladribine and Cytarabine and then received salvage hematopoietic stem cell transplantation (HSCT), but relapsed only half a month after a transient remission post-HSCT...Our in vitro drug toxicity assays demonstrated that ALK/ROS1 inhibitors Ceritinib and Crizotinib were the most effective in treating primary samples of the patient comparing to chemotherapy and VA...In summary, to our knowledge, this is the first characterization of TFG-ROS1 fusion as a novel oncogenic driver of myeloid leukemia. Our analysis elucidate that TFG-ROS1 fusion is a rare but recurrent oncogenic driver of human leukemia through the MEK/ERK signaling axis, and this fusion protein can be effectively targeted by ALK/ROS1 inhibitors.
- |||||||||| Precision Medicine Decision-Making in Metastatic Non-Small Cell Lung Cancer at Portuguese Hospitals () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_3338;
First-line decision for ROS1 translocation, BRAF V600 mutation and RET translocation is crizotinib (91%), dabrafenib+trametinib (64%) and selpercatinib (64%), respectively. At most of the Portuguese hospitals, the search for genetic variants and respective technique and timing of the test, as well as the therapeutic options used, generally follows ESMO
- |||||||||| Cost of Managing Brain Metastases in Patients With ALK+ aNSCLC First-Line Tyrosine Kinase Inhibitors (TKIS) in Sweden () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_1195;
Consistent with the data from phase 3 trials where the cumulative incidence of BM progression with 1L lorlatinib is lower than other TKIs, these longitudinal cost data demonstrate that 1L lorlatinib leads to lower management cost of BM in ALK+ aNSCLC patients compared to other 1L TKIs. Cost savings increase significantly over time and are biggest in patients without baseline BM, reflecting the protective effect of lorlatinib on brain metastases.
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Alecensa (alectinib) / Roche
Cost of Managing Brain Metastases in Patients With ALK-Positive Advanced NSCLC With First-Line ALK Tyrosine Kinase Inhibitors (TKIs) in China () - Nov 4, 2024 - Abstract #ISPOREU2024ISPOR_EU_800; OBJECTIVES: This study estimates the costs of managing brain metastases (BM) in patients with ALK-positive advanced non-small-cell lung cancer (aNSCLC) receiving lorlatinib, crizotinib, and alectinib as first-line treatment in China. Due to the lower CIR of BM progression with lorlatinib, significant savings in annual BM management costs were observed from year 1 to 4 in patients who received first-line lorlatinib in China, and are biggest in patients without BM, consistent with the known BM protective effect of lorlatinib.
- |||||||||| Xalkori (crizotinib) / Pfizer, imifoplatin (PT-112) / Promontory Therap
Journal: Pleiotrophin Activates cMet- and mTORC1-Dependent Protein Synthesis through PTPRZ1-The Role of ???3 Integrin. (Pubmed Central) - Oct 16, 2024 The ?v?3 integrin blocking antibody LM609 and the peptide PTN112-136, both known to bind to ???3 and inhibit PTN-induced endothelial cell migration, increase cMet phosphorylation and activate mTORC1, suggesting that cMet and mTORC1 activation are required but are not sufficient to stimulate cell migration. Overall, our data highlight novel aspects of the signaling pathway downstream of the PTN/PTPRZ1 axis that regulates endothelial cell functions.
- |||||||||| Xalkori (crizotinib) / Pfizer, Tabrecta (capmatinib) / Novartis, Tepmetko (tepotinib) / EMD Serono
OUTCOME AND TRANSCRIPTOMIC FEATURES OF DUAL EGFR AND MET BLOCKADE IN NSCLC (BALLROOM 2) - Oct 11, 2024 - Abstract #ASCOMOS2024ASCOMOS_176; CONCLUSION Our data suggests a potential benefit of adding MET inhibitor while continuing EGFR-TKI. Possible predictive factors are MET polysomy, high tumor content, and TRU subtype.
- |||||||||| Xalkori (crizotinib) / Pfizer
Journal: Radiologic findings of an adolescent epithelioid inflammatory myofibroblastic sarcoma. (Pubmed Central) - Oct 8, 2024 In addition to the imaging features, we describe the surgical findings, the pathologic features of the tumor, and the oncologic treatment of this patient. This case highlights the importance of including rare tumors such as epithelioid inflammatory myofibroblastic sarcoma as a potential differential consideration of an avidly enhancing homogenous abdominal mass in an adolescent.
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer
P3 data, Journal, Metastases: Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. (Pubmed Central) - Oct 7, 2024 After 5 years of follow-up, median PFS has yet to be reached in the lorlatinib group, corresponding to the longest PFS ever reported with any single-agent molecular targeted treatment in advanced NSCLC and across all metastatic solid tumors. These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced ALK-positive NSCLC and set a new benchmark for targeted therapies in cancer.
- |||||||||| Xalkori (crizotinib) / Pfizer, Rozlytrek (entrectinib) / Roche
Journal: Response to Crizotinib After Entrectinib Resistance in ROS1-Rearranged, MET-Amplified Lung Adenocarcinoma. (Pubmed Central) - Oct 7, 2024 These results coupled with prolonged intracranial efficacy and absence of new safety signals represent an unprecedented outcome for patients with advanced ALK-positive NSCLC and set a new benchmark for targeted therapies in cancer. Crizotinib successfully overcomes MET amplification in ROS1-rearranged NSCLC after entrectinib failure.
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer
Journal: Discovery of Oral Degraders of the ROS1 Fusion Protein with Potent Activity against Secondary Resistance Mutations. (Pubmed Central) - Oct 3, 2024 The degrader can effectively inhibit ROS1-dependent cell proliferation and tumor growth by degrading the ROS1 kinase, thereby eliminating the active phospho-ROS1. More importantly, the degradation-based therapeutic modality can overcome on-target mutation resistance to tyrosine kinase inhibitors by efficient degradation of the mutated kinase to achieve greater potency than inhibition.
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