- |||||||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer
Trial termination, Combination therapy, IO biomarker, Metastases: Study to Evaluate Safety, Efficacy, Pharmacokinetics And Pharmacodynamics Of Avelumab In Combination With Either Crizotinib Or PF-06463922 In Patients With NSCLC. (Javelin Lung 101) (clinicaltrials.gov) - Apr 6, 2023 P1b/2, N=43, Terminated, Completed --> Terminated; The study was terminated since there was no need for further safety or efficacy data to be collected. The participants having benefit from the Investigational treatments have been moved to a continuation study (NCT05059522)
- |||||||||| Lorbrena (lorlatinib) / Pfizer
P1 data, Journal: Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results. (Pubmed Central) - Apr 4, 2023 P1 Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib...The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12?months to <18?years); lorlatinib as a single agent in adults (?18?years); and lorlatinib in combination with topotecan/cyclophosphamide in children (<18?years)...The single-agent response rate (complete/partial/minor) for <18?years was 30%; for ?18?years, 67%; and for chemotherapy combination in <18?years, 63%; and 13 of 27 (48%) responders achieved MIBG complete responses, supporting lorlatinib's rapid translation into active phase 3 trials for patients with newly diagnosed high-risk, ALK-driven neuroblastoma. ClinicalTrials.gov registration: NCT03107988 .
- |||||||||| alkotinib (ZG0418) / Suzhou Zelgen
Trial completion date, Trial primary completion date, Metastases: Study of Alkotinib in Patients With Advanced Non Small Cell Lung Cancer (clinicaltrials.gov) - Apr 3, 2023 P1, N=18, Recruiting, ClinicalTrials.gov registration: NCT03107988 . Trial completion date: May 2023 --> May 2024 | Trial primary completion date: Feb 2023 --> Feb 2024
- |||||||||| Xalkori (crizotinib) / Pfizer
A Case of a Rare Benign Myofibroblastic Tumor of the Lung (Walter E. Washington Convention Center, Area L, Hall C (Lower Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_5836; Our case will add to the current literature. This was a challenging case given that she had a diagnosis of sarcoidosis, and the lesion was very significant PET-avid.
- |||||||||| Lorbrena (lorlatinib) / Pfizer
Trial completion date, Metastases: A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations (clinicaltrials.gov) - Mar 20, 2023 P2, N=334, Active, not recruiting, Additional studies could confirm these results for dasatinib, everolimus, pazopanib and ruxolitinib, and particularly for the two medicinal products with results slightly above the significance threshold, namely, crizotinib and vemurafenib, in our sensitivity analyses. Trial completion date: Feb 2023 --> May 2023
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer
Identification of the novel TENM3-ALK fusion in an AYA case with ALK rearranged neuroblastoma (Section 41; Poster Board #22) - Mar 14, 2023 - Abstract #AACR2023AACR_8256; We determined whether TENM3-ALK affects transformation and proliferation using a soft agar colony formation assay. As expected, the cells that expressed an empty vector and wild type ALK line did not produce a considerable number of colonies, whereas TENM3-ALK transfected cells showed anchorage-independent growth, resulting in the production of a higher number of colonies .The evidence for the role of ALK receptor signaling in stimulating neuroblastoma tumor cell growth and the demonstrated in vitro and in vivo efficacy of the ALK selective inhibitors in this study provide biological and clinical justification for the further exploration of this combination and testing in patients with recurrent or refractory neuroblastoma.
- |||||||||| JQ-1 / Roche, Xalkori (crizotinib) / Pfizer
Combined inhibition of BRD4 and FAK1 as a novel therapeutic strategy for neurofibromatosis type 2 related schwannomas (Section 35; Poster Board #17) - Mar 14, 2023 - Abstract #AACR2023AACR_8013; Moreover, this combination resulted in selective inhibition of NF2-null Schwann cell proliferation when compared to wild-type Schwann cells in vitro, when compared to either drug alone. Our preliminary data suggest that combined targeting of BET and FAK1 may offer a potential therapeutic option for the treatment of NF2-related schwannomas.
- |||||||||| Xalkori (crizotinib) / Pfizer, Avastin (bevacizumab) / Roche, Stivarga (regorafenib) / Bayer
Expanding the 3D ex vivo patient tissue platform toolbox for (immuno)-oncology drug testing (Section 2; Poster Board #21) - Mar 14, 2023 - Abstract #AACR2023AACR_7712; Despite tissue quality remaining a challenge for many primary ex vivo assays, the gentle processing and short-term 3D culturing in our EVPT platform preserves the rich TME in a wide range of tumors. This makes our EVPT platform an innovative and translational tool for complex (immuno)-oncology drug testing in multiple cancer indications.
- |||||||||| Xalkori (crizotinib) / Pfizer
Crizotinib (C) in patients (pts) with solid tumors with MET amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study (Section 47; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_6043; Our findings suggest that targeting TWIST1 may be an effective therapeutic strategy to overcome HGF-MET-driven resistance in MET-driven NSCLC. C did not meet prespecified criteria to declare a signal of activity in pts with solid tumors with MET amp or mut.Table: Baseline Characteristics (N=31); Efficacy Outcomes (n=28); Toxicity Outcomes (N=31)Median (Med) age, years (range)61 (30, 82)Female, %16 (52)ECOG PS, %015 (48)112 (39)24 (13)Prior systemic regimens, %13 (10)25 (16)?323 (74)DC rate, % (OR and SD16+) (1-sided 90% CI)21 (12, 100)Objective response rate, % (95% CI)7 (1, 24)Med PFS, wks (95% CI)8 (8, 13)Med OS, wks (95% CI)37 (26, 68)Duration of response, wks (n=2)14 and 20Med duration SD, wks (n=4)27 (26, 28)Number of pts1 with tx-related grade 3 adverse or any grade serious adverse eventAE25 (16)SAE33 (10)1Pts may have experienced one or more events2ALT increase, diarrhea and all SAEs3Acute kidney injury, ALT increase, AST increase, blood bilirubin increase, creatinine increase, dehydration, fatigue, GGT increase, hyperkalemia, nausea, sinus bradycardia
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Overcoming cetuximab resistance in colorectal cancer through inhibition of HGF processing (Section 9; Poster Board #12) - Mar 14, 2023 - Abstract #AACR2023AACR_5256; We are currently testing if upstream inhibition with recombinant human HAI-1 addition can suppress HGF cleavage and overcome cetuximab resistance induced by HGF overexpression. Collectively, our findings suggest that inhibiting HGF cleavage and processing may be a unique strategy for overcoming EGFR-targeted therapy resistance in colorectal cancer.
- |||||||||| TY-2136b / TYK Medicines, Livzon Pharma
TY-2136b, a next generation ROS1/TRK/ALK inhibitor, potently inhibits kinase and cell proliferation activities of tumor cells bearing drug-dependent acquired mutations (Section 44; Poster Board #10) - Mar 14, 2023 - Abstract #AACR2023AACR_4725; In vivo studies, TY-2136b showed dose-dependent anti-tumor effect at the dose of 5, 10, and 20 mg/kg, bid, in xenograft tumor models carrying ROS1 G2032R and TRKA G595R mutation, and was more effective than Crizotinib and LOXO-101 at testing dose, and showed better efficacy than TPX-0005 in higher dose...Currently, TY-2136b is under first-in-human clinical investigations in the US and China. * To Whom Correspondence should be addressed to: Jun Li, Chengshan Niu and Yusheng Wu
- |||||||||| Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis
Treatment-free remission after discontinuation of ALK tyrosine kinase inhibitors (TKIs) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) (Section 40; Poster Board #23) - Mar 14, 2023 - Abstract #AACR2023AACR_3476; MRD-guideddiscontinuation decision may be considered for ALK-positive ALCL patients treated with ALK inhibitors who had undetectable MRD.Table 1. Summary of patient characteristics and outcomes of ALK TKI discontinuationNo.SexAge at diagnosisAnn Arbor stageALK TKILines of prior therapyTreatment duration of ALK TKI (months)Reason for cessationDuration of ALK TKI cessation (months)Best response to ALK TKITime of MRD assessment after TKI cessationMRD after TKI cessation1M22IIBCrizotinib393.9Fertility27.8CR5.6Negative2F20IVBCrizotinib190.9Fertility25.9CR0.0Negative3M23IVCeritinib142.7Adverse event61.9CR61.9Negative4F58IVCrizotinib31.7Cost86.6CR72.1Negative5F64IVBCrizotinib113.6Cost31.0CR14.4Negative6M75IVCrizotinib211.7Cost80.2CR62.0Negative
- |||||||||| Xalkori (crizotinib) / Pfizer, Orpathys (savolitinib) / AstraZeneca, Hutchmed
Comprehensive characterization of MET exon 14 skipping mutations in non-small cell lung cancer (Section 38; Poster Board #23) - Mar 14, 2023 - Abstract #AACR2023AACR_2370; MET focal amplification by NGS tests might be a feasible and powerful biomarker to identify LC patients who benefit from MET inhibitors. In this study, we characterized MET?ex14 in a large cohort of NSCLC patients and explored potential primary and secondary resistance mechanisms to savolitinib and crizotinib, which may facilitate drug development and help inform clinical actions.
- |||||||||| Xalkori (crizotinib) / Pfizer
Functional enrichment analysis of somatic mutations identifies novel risk factors for pediatric neuroblastoma (Section 32; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_2120; Gene sets defined by the function of their products in ALK signaling, as well as alteration in cells treated with Crizotinib, an inhibitor of receptor tyrosine kinases including ALK, both displayed highly significant association with altered survival...Of these, eight showed a more significant association with altered survival than the ALK signaling pathway itself. These results identify novel risk factors associated with reduced survival in pediatric neuroblastoma patientsand illustrate the potential of systems-level analysis to generate insight into the biology of heterogeneous cancers.
- |||||||||| Xalkori (crizotinib) / Pfizer
Emergency Steroid Treatment of Superior Vena Cava Syndrome Secondary to Malignant Mediastinal Mass Resulting In Diagnostic Uncertainty Due to Pre-Biopsy Administration () - Mar 14, 2023 - Abstract #PAS2023PAS_3255; He started a second cycle of chemotherapy with bleomycin, etoposide, and cisplatin (BEP) per AGCT1532 however, again, had poor response...He received triple intrathecal chemotherapy once followed by treatment per ANHL12P1 with crizotinib, dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide with good response... A 17 year old boy
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