المؤلفون: Piha-Paul, Sarina A., Tseng, Chieh, Tran, Hai T., Gao, Meng, Karp, Daniel D., Subbiah, Vivek, Tsimberidou, Apostolia Maria, Kawedia, Jitesh D., Fu, Siqing, Pant, Shubham, Yap, Timothy A., Morris, Van K., Kee, Bryan K., Blum Murphy, Mariela, Lim, JoAnn, Meric-Bernstam, Funda

المساهمون: Puma Biotechnology

المصدر: Cancer Chemotherapy and Pharmacology ; volume 92, issue 2, page 107-118 ; ISSN 0344-5704 1432-0843

مصطلحات موضوعية: Pharmacology (medical), Cancer Research, Pharmacology, Toxicology, Oncology

الوصف: Purpose Aberrant alterations of ERBB receptor tyrosine kinases lead to tumorigenesis. Single agent therapy targeting EGFR or HER2 has shown clinical successes, but drug resistance often develops due to aberrant or compensatory mechanisms. Herein, we sought to determine the feasibility and safety of neratinib and trametinib in patients with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation and KRAS mutation. Methods Patients with actionable somatic mutations or amplifications in ERBB genes or actionable KRAS mutations were enrolled to receive neratinib and trametinib in this phase I dose escalation trial. The primary endpoint was determination of the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Secondary endpoints included pharmacokinetic analysis and preliminary anti-tumor efficacy. Results Twenty patients were enrolled with a median age of 50.5 years and a median of 3 lines of prior therapy. Grade 3 treatment-related toxicities included: diarrhea (25%), vomiting (10%), nausea (5%), fatigue (5%) and malaise (5%). The MTD was dose level (DL) minus 1 (neratinib 160 mg daily with trametinib 1 mg, 5 days on and 2 days off) given 2 DLTs of grade 3 diarrhea in DL1 (neratinib 160 mg daily with trametinib 1 mg daily). The treatment-related toxicities of DL1 included: diarrhea (100%), nausea (55.6%) and rash (55.6%). Pharmacokinetic data showed trametinib clearance was significantly reduced leading to high drug exposures of trametinib. Two patients achieved stable disease (SD) ≥ 4 months. Conclusion Neratinib and trametinib combination was toxic and had limited clinical efficacy. This may be due to suboptimal drug dosing given drug–drug interactions. Trial registration ID: NCT03065387.

الإتاحة: https://doi.org/10.1007/s00280-023-04545-4Test

المؤلفون: Popat, Uday R., Saliba, Rima M., Mehta, Rohtesh S., Alousi, Amin M., Al-Atrash, Gheath, Bashir, Qaiser, Chen, Julianne, Gulbis, Alison M., Hosing, Chitra M., Im, Jin S., Kebriaei, Partow, Khouri, Issa F., Kawedia, Jitesh D., Marin, David, Nieto, Yago, Olson, Amanda, Oran, Betul, Ramdial, Jeremy, Saini, Neeraj Y., Srour, Samer A., Rezvani, Katayoun, Qazilbash, Muzaffar H., Kantarjian, Hagop, Andersson, Borje S., Champlin, Richard E., Shpall, Elizabeth J.

المصدر: Transplantation and Cellular Therapy ; volume 29, issue 2, page S164-S165 ; ISSN 2666-6367

مصطلحات موضوعية: Transplantation, Cell Biology, Hematology, Molecular Medicine, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/s2666-6367Test(23)00281-6
https://api.elsevier.com/content/article/PII:S2666636723002816?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666636723002816?httpAccept=text/plainTest

المؤلفون: Kawedia, Jitesh D., Liu, Xiaoqian, Ramdial, Jeremy, Srour, Samer A., Mehta, Rohtesh S., Popat, Uday R., Nieto, Yago, Saini, Neeraj Y., Kebriaei, Partow, Knape, Cristina, Gulbis, Alison M., Champlin, Richard E., Shpall, Elizabeth J., Qazilbash, Muzaffar H., Bashir, Qaiser

المصدر: Transplantation and Cellular Therapy ; volume 29, issue 2, page S438-S439 ; ISSN 2666-6367

مصطلحات موضوعية: Transplantation, Cell Biology, Hematology, Molecular Medicine, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/s2666-6367Test(23)00660-7
https://api.elsevier.com/content/article/PII:S2666636723006607?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666636723006607?httpAccept=text/plainTest

المؤلفون: Popat, Uday R., Saliba, Rima M., Mehta, Rohtesh S., Alousi, Amin M., Al-Atrash, Gheath, Bashir, Qaiser, Hosing, Chitra M., Gulbis, Alison M., Im, Jin S., Kebriaei, Partow, Khouri, Issa F., Kawedia, Jitesh D., Marin, David, Nieto, Yago, Olson, Amanda, Oran, Betul, Ramdial, Jeremy, Saini, Neeraj Y., Shigle, Terri Lynn, Srour, Samer A., Rezvani, Katayoun, Qazilbash, Muzaffar H., Andersson, Borje S., Shpall, Elizabeth J., Champlin, Richard E.

المصدر: Transplantation and Cellular Therapy ; volume 29, issue 2, page S167 ; ISSN 2666-6367

مصطلحات موضوعية: Transplantation, Cell Biology, Hematology, Molecular Medicine, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/s2666-6367Test(23)00284-1
https://api.elsevier.com/content/article/PII:S2666636723002841?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666636723002841?httpAccept=text/plainTest

المؤلفون: Kawedia, Jitesh D., Liu, Xiaoqian, Sui, Dawen, Gulbis, Alison M., Ramdial, Jeremy, Srour, Samer A., Popat, Uday R., Nieto, Yago, Kebriaei, Partow, Saini, Neeraj Y., Lin, Paul, Aljawai, Yosra, Pasvolsky, Oren, Lee, Hans C., Orlowski, Robert Z., Thomas, Sheeba K., Patel, Krina K., Knape, Cristina, Delgado, Ruby, Champlin, Richard E., Shpall, Elizabeth J., Qazilbash, Muzaffar H., Thall, Peter, Bashir, Qaiser

المصدر: Transplantation and Cellular Therapy ; volume 30, issue 2, page S96 ; ISSN 2666-6367

مصطلحات موضوعية: Transplantation, Cell Biology, Hematology, Molecular Medicine, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/j.jtct.2023.12.153Test
https://api.elsevier.com/content/article/PII:S2666636723018882?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666636723018882?httpAccept=text/plainTest

المؤلفون: Johnson, Faye M, Janku, Filip, Gouda, Mohamed A, Tran, Hai T, Kawedia, Jitesh D, Schmitz, Debora, Streefkerk, Hendrik, Lee, J Jack, Andersen, Clark R, Deng, Defeng, Rawal, Seema, Shah, Pooja A, El-Naggar, Adel K, Johnson, Jason M, Frederick, Mitchell J

المصدر: The Oncologist ; volume 27, issue 12, page 1004-e926 ; ISSN 1083-7159 1549-490X

الوصف: Background PI3K/mTOR inhibition leads to apoptosis of NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC) cells. We tested the efficacy of the PI3K/mTOR inhibitor bimiralisib in patients with NOTCH1-mutant HNSCC. Methods Patients with recurrent/metastatic NOTCH1-mutant HNSCC who had progressed during chemotherapy and immunotherapy received bimiralisib until unacceptable toxicity or progression. To assess whether NOTCH1 mutations can be detected in blood, we measured circulating tumor DNA (ctDNA). To assess activated NOTCH1 protein levels, we quantitated cleaved NOTCH1 (cl-NOTCH) by immunohistochemistry. Results Eight patients were treated, and 6 were evaluable for response. The objective response rate was 17%. For all 8 patients, median progression-free and overall survival was 5 and 7 months, respectively. Bimiralisib was well tolerated, with expected hyperglycemia. Pharmacokinetic values were consistent with published studies. NOTCH1 mutations were detected in 83.3% of ctDNA. Staining for tumor cl-NOTCH1 was negative. The trial closed early due to sponsor insolvency. Conclusion Although the trial was small, outcomes with bimiralisib were better than the historical standard of care; Results will need to be confirmed in a larger trial. The lack of cl-NOTCH1 was consistent with loss-of-function mutations and validated our mutation function algorithm. The ability to detect NOTCH1 mutations in blood will help future studies. (ClinicalTrials.gov Identifier: NCT03740100).

الإتاحة: https://doi.org/10.1093/oncolo/oyac185Test
https://academic.oup.com/oncolo/article-pdf/27/12/1004/47751518/oyac185.pdfTest

المؤلفون: Popat, Uday R, Mehta, Rohtesh S., Bassett, Roland, Alousi, Amin M., Al-Atrash, Gheath, Bashir, Qaiser, Hosing, Chitra, Im, Jin Seon, Kebriaei, Partow, Kawedia, Jitesh D, Khouri, Issa F., Marin, David, Nieto, Yago, Olson, Amanda, Oran, Betul, Ramdial, Jeremy, Saini, Neeraj Y, Srour, Samer A, Rezvani, Katayoun, Qazilbash, Muzaffar H., Shpall, Elizabeth J, Andersson, Borje S., Champlin, Richard E

المصدر: Transplantation and Cellular Therapy ; volume 28, issue 3, page S83-S84 ; ISSN 2666-6367

مصطلحات موضوعية: Transplantation, Cell Biology, Hematology, Molecular Medicine, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/s2666-6367Test(22)00257-3
https://api.elsevier.com/content/article/PII:S2666636722002573?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666636722002573?httpAccept=text/plainTest

المؤلفون: Kawedia, Jitesh D, Anderson, Telyssa, Popat, Uday R, Andersson, Borje S., Champlin, Richard E, Kebriaei, Partow

المصدر: Transplantation and Cellular Therapy ; volume 28, issue 3, page S461 ; ISSN 2666-6367

مصطلحات موضوعية: Transplantation, Cell Biology, Hematology, Molecular Medicine, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/s2666-6367Test(22)00756-4
https://api.elsevier.com/content/article/PII:S2666636722007564?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666636722007564?httpAccept=text/plainTest

المؤلفون: Popat, Uday R, Mehta, Rohtesh S., Bassett, Roland, Alousi, Amin M., Al-Atrash, Gheath, Bashir, Qaiser, Hosing, Chitra, Im, Jin Seon, Kebriaei, Partow, Kawedia, Jitesh D, Khouri, Issa F., Marin, David, Nieto, Yago, Olson, Amanda, Oran, Betul, Ramdial, Jeremy, Saini, Neeraj Y, Srour, Samer A, Valdez, Ben C., Rezvani, Katayoun, Qazilbash, Muzaffar H., Kadia, Tapan M, Kantarjian, Hagop, Shpall, Elizabeth J, Champlin, Richard E, Andersson, Borje S.

المصدر: Transplantation and Cellular Therapy ; volume 28, issue 3, page S293 ; ISSN 2666-6367

مصطلحات موضوعية: Transplantation, Cell Biology, Hematology, Molecular Medicine, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/s2666-6367Test(22)00539-5
https://api.elsevier.com/content/article/PII:S2666636722005395?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666636722005395?httpAccept=text/plainTest

المؤلفون: Lin, Steven H, Lin, Heather Y, Verma, Vivek, Xu-Welliver, Meng, Thall, Peter F, Yao, Luyang, Kim, Peter Y, Gombos, Dan S, Kawedia, Jitesh D, Komaki, Ritsuko, Gomez, Daniel R, Nguyen, Quynh-Nhu, O'Reilly, Michael S, Lu, Charles, Fossella, Frank V, Skoulidis, Ferdinandos, Zhang, Jianjun, Tsao, Anne S, Heymach, John V, Blumenschein, George R

المساهمون: National Cancer Institute, University of Texas MD Anderson Cancer Center

المصدر: Cancer Treatment and Research Communications ; volume 30, page 100514 ; ISSN 2468-2942

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.ctarc.2022.100514Test
https://api.elsevier.com/content/article/PII:S2468294222000065?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2468294222000065?httpAccept=text/plainTest