Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of SAR245408 (XL147), an Oral Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors

Shapiro, Geoffrey I.; Rodon, Jordi; Bedell, Cynthia; Kwak, Eunice L.; Baselga, Jose; Braña, Irene; Pandya, Shuchi S.; Scheffold, Christian; Laird, A. Douglas; Nguyen, Linh T.; Xu, Yi; Egile, Coumaran; Edelman, Gerald

doi:10.1158/1078-0432.ccr-13-1777

Cited by 154PI3K/AKT/mTOR signaling in cancerAdvanced Breast Cancer TherapiesMetabolism, Diabetes, and Cancer

Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of SAR245408 (XL147), an Oral Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors

Shapiro, Geoffrey I., Rodon, Jordi, Bedell, Cynthia, Kwak, Eunice L., Baselga, Jose, Braña, Irene, Pandya, Shuchi S., Scheffold, Christian +5 more·2014·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-13-1777

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Abstract

Purpose: SAR245408 is a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor. This phase I study determined the maximum tolerated dose (MTD) of two dosing schedules [first 21 days of a 28-day period (21/7) and continuous once-daily dosing (CDD)], pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy. Experimental Design: Patients with refractory advanced solid malignancies were treated with SAR245408 using a 3 + 3 design. Pharmacokinetic parameters were determined after single and repeated doses. Pharmacodynamic effects were evaluated in plasma, hair sheath cells, and skin and tumor biopsies. Results: Sixty-nine patients were enrolled. The MTD of both schedules was 600 mg; dose-limiting toxicities were maculopapular rash and hypersensitivity reaction. The most frequent drug-related adverse events included dermatologic toxicities, diarrhea, nausea, and decreased appetite. Plasma pharmacokinetics showed a median time to maximum concentration of 8 to 22 hours, mean terminal elimination half-life of 70 to 88 hours, and 5- to 13-fold accumulation after daily dosing (first cycle). Steady-state concentration was reached between days 15 and 21, and exposure was dose-proportional with doses up to 400 mg. SAR245408 inhibited the PI3K pathway (∼40%–80% reduction in phosphorylation of AKT, PRAS40, 4EBP1, and S6 in tumor and surrogate tissues) and, unexpectedly, also inhibited the MEK/ERK pathway. A partial response was seen in one patient with advanced non–small cell lung cancer. Eight patients were progression-free at 6 months. Pharmacodynamic and clinical activity were observed irrespective of tumor PI3K pathway molecular alterations. Conclusions: SAR245408 was tolerable at doses associated with PI3K pathway inhibition. The recommended phase II dose of the capsule formulation is 600 mg administered orally with CDD. Clin Cancer Res; 20(1); 233–45. ©2013 AACR.

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The PI3K inhibitor XL147 inhibited the PI3K pathway with a 40-80% reduction in phosphorylation of AKT and 4EBP1 in tumours and unexpectedly inhibited the MEK/ERK pathway in a phase I trial.
“For example, the PI3K inhibitor XL147 was reported to inhibit the PI3K pathway with a 40–80% reduction in the phosphorylation of AKT and 4EBP1 in tumours and unexpectedly inhibited the MEK/ERK pathway in a phase I trial [111].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [111]

New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660 · see citing works
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621 · see citing works
High Frequency of Mutations of the PIK3CA Gene in Human Cancers
Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A. F., Powell, S. M., Riggins, G. J., et al. (2004) · Science · doi:10.1126/science.1096502 · Cited by 3,448 · see citing works
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330 · see citing works
Targeting the phosphoinositide 3-kinase pathway in cancer
Liu, P., Cheng, H.-L. M., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,722 · see citing works
Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954 · see citing works
Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
Carracedo, A., Ma, L., Teruya-Feldstein, J., Rojo, F., Salmena, L., Alimonti, A., Egia, A., Sasaki, A. T., Thomas, G., Kozma, S. C., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34739 · Cited by 1,381 · see citing works
Self-citation
The PI3K Pathway As Drug Target in Human Cancer
Courtney, K. D., Corcoran, R. B., & Engelman, J. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.3641 · Cited by 1,235 · see citing works
Role of Phosphoinositide 3-OH Kinase in Cell Transformation and Control of the Actin Cytoskeleton by Ras
Rodriguez‐Viciana, P., Warne, P. H., Khwaja, A., Marte, B. M., Pappin, D., Das, P., Waterfield, M. D., Ridley, A. J., & Downward, J. (1997) · Cell · doi:10.1016/s0092-8674(00)80226-3 · Cited by 1,063 · see citing works
PTEN loss in the continuum of common cancers, rare syndromes and mouse models
Hollander, M. C., Blumenthal, G. M., & Dennis, P. A. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3037 · Cited by 793 · see citing works
Phase I, Dose-Escalation Study of BKM120, an Oral Pan-Class I PI3K Inhibitor, in Patients With Advanced Solid Tumors
Bendell, J. C., Rodon, J. A., Burris, H. A., de Jonge, M. J. A., Verweij, J., Birle, D. C., Demanse, D., Buck, S. S. D., Ru, Q. C., Peters, M., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.36.1360 · Cited by 687 · see citing works
Self-citation
Class I PI3K in oncogenic cellular transformation
Zhao, L., & Vogt, P. K. (2008) · Oncogene · doi:10.1038/onc.2008.244 · Cited by 598 · see citing works
First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors
Yap, T. A., Li, Y., Patnaik, A., Fearen, I., Olmos, D., Papadopoulos, K. P., Baird, R. D., Delgado, L., Taylor, A. B., Lupinacci, L. C., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.5263 · Cited by 540 · see citing works
Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor
Maira, S.-M., Pecchi, S., Huang, A., Burger, M. T., Knapp, M. S., Sterker, D., Schnell, C., Guthy, D. A., Nagel, T., Wiesmann, M., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0474 · Cited by 533 · see citing works
The p110β isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110γ
Guillermet‐Guibert, J., Björklöf, K., Salpekar, A., Gonella, C., Ramadani, F., Bilancio, A., Meek, S. E., Smith, A. J. H., Okkenhaug, K., & Vanhaesebroeck, B. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707761105 · Cited by 345 · see citing works
Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.
McCubrey, J. A., Steelman, L. S., Chappell, W. H., Abrams, S. L., Montalto, G., Cervello, M., Nicoletti, F., Fagone, P., Malaponte, G., Mazzarino, M. C., et al. (2012) · Oncotarget · doi:10.18632/oncotarget.652 · Cited by 310 · see citing works
Multiple Mutations and Bypass Mechanisms Can Contribute to Development of Acquired Resistance to MET Inhibitors
Qi, J., McTigue, M. A., Rogers, A. M., Lifshits, E., Christensen, J. G., Janne, P. A., & Engelman, J. A. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-1623 · Cited by 218 · see citing works
A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Hong, D. S., Bowles, D. W., Falchook, G. S., Messersmith, W. A., George, G. C., O’Bryant, C. L., Vo, A. C. H., Klucher, K. M., Herbst, R. S., Eckhardt, S., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0714 · Cited by 169 · see citing works
Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia
Brown, J. R., Hanna, M., Tesar, B. M., Werner, L. L., Pochet, N. L. M. M., Asara, J. M., Wang, Y. E., Cin, P. D., Fernandes, S. M., Thompson, C., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2342 · Cited by 85 · see citing works
PIK3CA Genotype and a PIK3CA Mutation-Related Gene Signature and Response to Everolimus and Letrozole in Estrogen Receptor Positive Breast Cancer
Loi, S., Michiels, S., Baselga, J. M., Bartlett, J. M. S., Singhal, S. K., Sabine, V. S., Sims, A. H., Sahmoud, T., Dixon, J. M., Piccart, M. J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053292 · Cited by 84 · see citing works
Self-citation
A phase I dose-escalation study of XL147 (SAR245408), a PI3K inhibitor administered orally to patients (pts) with advanced malignancies.
Edelman, G. M., Bedell, C., Shapiro, G. I., Pandya, S. S., Kwak, E. L., Scheffold, C., Nguyen, L. T., Laird, A., Baselga, J. M., & Rodon, J. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.3004 · Cited by 77 · see citing works
Self-citation
Targeting the EGFR and the PKB pathway in cancer
Klein, S., & Levitzki, A. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.12.006 · Cited by 70 · see citing works
Safety, pharmacokinetics, and preliminary activity of the α-specific PI3K inhibitor BYL719: Results from the first-in-human study.
Gonzalez-Angulo, A. M., Juric, D., Argilés, G., Schellens, J. H. M., Burris, H. A., Berlin, J. D., Middleton, M. R., Schüler, M., van Geel, R. M. J. M., Helgason, T., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.2531 · Cited by 52 · see citing works
Self-citation
Preferential chemosensitization of PTEN‐mutated prostate cells by silencing the Akt kinase
Priulla, M., Calastretti, A., Bruno, P., Azzariti, A., Paradiso, A., Canti, G. L., & Nicolin, A. (2007) · The Prostate · doi:10.1002/pros.20566 · Cited by 50 · see citing works
PI3K keeps the balance between metabolism and cancer
Braccini, L., Ciraolo, E., Martini, M., Pirali, T., Germena, G., Rolfo, K., & Hirsch, E. (2012) · Advances in Biological Regulation · doi:10.1016/j.jbior.2012.04.002 · Cited by 46 · see citing works
Abstract LB-64: GDC-0032, a beta isoform-sparing PI3K inhibitor: Results of a first-in-human phase Ia dose escalation study.
Juric, D., Krop, I. E., Ramanathan, R. K., Xiao, J. J., Sanabria, S., Wilson, T. R., Choi, Y., Parmar, H. R., Hsu, J. Y., Baselga, J. M., et al. (2013) · Cancer Research · doi:10.1158/1538-7445.am2013-lb-64 · Cited by 43 · see citing works
Self-citation
Development of a robust flow cytometry-based pharmacodynamic assay to detect phospho-protein signals for phosphatidylinositol 3-kinase inhibitors in multiple myeloma
Li, C., Takahashi, C., Zhang, L., Huseni, M. A., Stankovich, B. L., Mashhedi, H., Lee, J., French, D. M., Anderson, J. E., Kim, D. S., et al. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-76 · Cited by 9 · see citing works

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PI3K/AKT signaling pathway and cancer: an updated review
Martini, M., Santis, M. C. D., Braccini, L., Gulluni, F., & Hirsch, E. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.912836 · Cited by 1,176 · see citing works
Targeting the PI3K pathway in cancer: are we making headway?
Janku, F., Yap, T. A., & Meric-Bernstam, F. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.28 · Cited by 1,033 · see citing works
The relation between PI3K/AKT signalling pathway and cancer
Noorolyai, S., Shajari, N., Baghbani, E., Sadreddini, S., & Baradaran, B. (2019) · Gene · doi:10.1016/j.gene.2019.02.076 · Cited by 661 · see citing works
Targeting the PI3K/Akt/mTOR pathway in non‐small cell lung cancer (NSCLC)
Tan, A. C. (2020) · Thoracic Cancer · doi:10.1111/1759-7714.13328 · Cited by 538 · see citing works
Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors
LoRusso, P. M. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.0018 · Cited by 467 · see citing works
Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer
Fumarola, C., Bonelli, M. A., Petronini, P. G., & Alfieri, R. R. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.05.011 · Cited by 463 · see citing works
Phosphatidylinositol 3-Kinase α–Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study
Juric, D., Rodon, J. A., Tabernero, J. M., Jankú, F., Burris, H. A., Schellens, J. H. M., Middleton, M. R., Berlin, J. D., Schüler, M., Gil-Martín, M., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.72.7107 · Cited by 434 · see citing works
Self-citation
Targeting RTK Signaling Pathways in Cancer
Regad, T. (2015) · Cancers · doi:10.3390/cancers7030860 · Cited by 385 · see citing works
PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux
O’Donnell, J. S., Massi, D., Teng, M. W. L., & Mandalà, M. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.04.015 · Cited by 382 · see citing works
First-in-Human Phase I Study of Pictilisib (GDC-0941), a Potent Pan–Class I Phosphatidylinositol-3-Kinase (PI3K) Inhibitor, in Patients with Advanced Solid Tumors
Sarker, D., Ang, J. E., Baird, R. D., Kristeleit, R. S., Shah, K. J., Moreno, V., Clarke, P. A., Raynaud, F. I., Levy, G. G., Ware, J. A., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0947 · Cited by 361 · see citing works
Quantitative Optical Imaging of Primary Tumor Organoid Metabolism Predicts Drug Response in Breast Cancer
Walsh, A. J., Cook, R. S., Sanders, M. E., Aurisicchio, L., Ciliberto, G., Arteaga, C. L., & Skala, M. C. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0663 · Cited by 313 · see citing works
Current State of Breast Cancer Diagnosis, Treatment, and Theranostics
Bhushan, A., Gonsalves, A., & Menon, J. U. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050723 · Cited by 316 · see citing works
PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects
Mishra, R., Patel, H. M., Alanazi, S., Kilroy, M. K., & Garrett, J. T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073464 · Cited by 293 · see citing works
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Phosphoinositide 3-kinase (PI3K) pathway inhibitors in solid tumors: From laboratory to patients
Jankú, F. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.07.005 · Cited by 245 · see citing works
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PI3K-AKT-mTOR inhibitors in breast cancers: From tumor cell signaling to clinical trials
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“Another PI3K inhibitor, SAR245408, has shown promising clinical activity in NSCLC [167].”
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Jimeno, A., Shirai, K., Choi, M., Laskin, J. J., Kochenderfer, M. D., Spira, A. I., Cline-Burkhardt, V. J. M., Winquist, E., Hausman, D. F., Walker, L. N., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu574 · Cited by 99 · see citing works
TAK ‐228 (formerly MLN 0128), an investigational oral dual TORC 1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non‐Hodgkin lymphoma, or Waldenström's macroglobulinemia
Ghobrial, I. M., Siegel, D. S. D., Vij, R., Berdeja, J. G., Richardson, P. G. G., Neuwirth, R. B., Patel, C. G., Zohren, F., & Wolf, J. L. (2016) · American Journal of Hematology · doi:10.1002/ajh.24300 · Cited by 99 · see citing works
Drug response in organoids generated from frozen primary tumor tissues
Walsh, A. J., Cook, R. S., Sanders, M. E., Arteaga, C. L., & Skala, M. C. (2016) · Scientific Reports · doi:10.1038/srep18889 · Cited by 98 · see citing works
Safety and Tolerability of Phosphatidylinositol-3-Kinase (PI3K) Inhibitors in Oncology
Curigliano, G., & Shah, R. R. (2019) · Drug Safety · doi:10.1007/s40264-018-0778-4 · Cited by 102 · see citing works
Targeting the genetic alterations of the PI3K–AKT–mTOR pathway: Its potential use in the treatment of bladder cancers
Houédé, N., & Pourquier, P. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.06.004 · Cited by 94 · see citing works
A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours.
Fazio, N., Buzzoni, R., Baudin, É., Antonuzzo, L., Hubner, R. A., Lahner, H., de Herder, W. W., Raderer, M., Teulé, À., Capdevila, J., et al. (2016) · PubMed · Cited by 85 · see citing works
Computer-Aided Targeting of the PI3K/Akt/mTOR Pathway: Toxicity Reduction and Therapeutic Opportunities
Li, T., & Wang, G. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151018856 · Cited by 84 · see citing works
Hyperglycemia Associated With Targeted Oncologic Treatment: Mechanisms and Management
Goldman, J. W., Mendenhall, M. A., & Rettinger, S. R. (2016) · The Oncologist · doi:10.1634/theoncologist.2015-0519 · Cited by 83 · see citing works
Targeted therapies for ER+/HER2- metastatic breast cancer
Yamamoto‐Ibusuki, M., Arnedos, M., & André, F. (2015) · BMC Medicine · doi:10.1186/s12916-015-0369-5 · Cited by 82 · see citing works
Novel drugs that target the metabolic reprogramming in renal cell cancer
van der Mijn, J. C., Panka, D. J., Geissler, A. K., Verheul, H. M. W., & Mier, J. W. (2016) · Cancer & Metabolism · doi:10.1186/s40170-016-0154-8 · Cited by 81 · see citing works
VPS34 stimulation of p62 phosphorylation for cancer progression
Jiang, X., Bao, Y., Liu, H., Kou, X., Zhang, Z., Sun, F., Qian, Z., Lin, Z., Li, X., Liu, X., et al. (2017) · Oncogene · doi:10.1038/onc.2017.295 · Cited by 82 · see citing works
A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer
Jimeno, A., Bauman, J. E., Weissman, C., Adkins, D. R., Schnadig, I. D., Beauregard, P., Bowles, D. W., Spira, A. I., Levy, B. P., Seetharamu, N., et al. (2015) · Oral Oncology · doi:10.1016/j.oraloncology.2014.12.013 · Cited by 78 · see citing works
PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation
Hou, X., Liu, Y., Liu, H., Chen, X., Liu, M., Che, H., Guo, F., Wang, C., Zhang, D., Wu, J., et al. (2015) · Scientific Reports · doi:10.1038/srep09065 · Cited by 75 · see citing works
KRAS-Mutant Non-Small Cell Lung Cancer: An Emerging Promisingly Treatable Subgroup
Xie, M., Xu, X., & Fan, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.672612 · Cited by 76 · see citing works
Prevalence of driver mutations in non-small-cell lung cancers in the People’s Republic of China
Wu, Y.-L. L. C., & Gou, L.-Y. (2014) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s40817 · Cited by 62 · see citing works
Dual PI3K/mTOR Inhibition in Colorectal Cancers with APC and PIK3CA Mutations
Foley, T. M., Payne, S. N., Pasch, C. A., Yueh, A. E., Hey, D. R. V. D., Korkos, D. P., Clipson, L. J., Maher, M. E., Matkowskyj, K. A., Newton, M. A., et al. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0256 · Cited by 62 · see citing works
Novel Emerging Molecular Targets in Non-Small Cell Lung Cancer
Rebuzzi, S. E., Zullo, L., Rossi, G., Grassi, M., Murianni, V., Tagliamento, M., Prelaj, A., Coco, S., Longo, L., Bello, M. G. D., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052625 · Cited by 61 · see citing works
Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer
Tolaney, S. M., Burris, H. A., Gartner, E. M., Mayer, I. A., Saura, C., Maurer, M., Ciruelos, E., García, A. A., Campana, F., Wu, B., et al. (2014) · Breast Cancer Research and Treatment · doi:10.1007/s10549-014-3248-4 · Cited by 59 · see citing works
Self-citation
New Insights into the Role of Exercise in Inhibiting mTOR Signaling in Triple‐Negative Breast Cancer
Agostini, D., Natalucci, V., Baldelli, G., Santi, M. D., Zeppa, S. D., Vallorani, L., Annibalini, G., Lucertini, F., Federici, A., Izzo, R., et al. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/5896786 · Cited by 60 · see citing works
The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models
Foster, P., Yamaguchi, K., Hsu, P. P., Qian, F., Du, X., Wu, J., Won, K.-A., Yu, P., Jaeger, C. T., Zhang, W., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0833 · Cited by 58 · see citing works
Self-citation
A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors
Aghajanian, C. A., Bell‐McGuinn, K. M., Burris, H. A., Siu, L. L., Stayner, L.-A., Wheler, J. J., Hong, D. S., Kurkjian, C. D., Pant, S., Santiago-Walker, A., et al. (2018) · Investigational New Drugs · doi:10.1007/s10637-018-0591-z · Cited by 58 · see citing works
Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma
Brown, J. R., Davids, M. S., Rodon, J. A., Abrisqueta, P., Kasar, S. N., Lager, J. J., Jiang, J., Égile, C., & Awan, F. T. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3262 · Cited by 55 · see citing works
Self-citation
New development of inhibitors targeting the PI3K/AKT/mTOR pathway in personalized treatment of non-small-cell lung cancer
Sun, Z., Wang, Z., Liu, X., & Wang, D. (2014) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000000172 · Cited by 52 · see citing works
Phosphatidylinositol 3-kinase (PI3K) inhibitors: a recent update on inhibitor design and clinical trials (2016–2020)
Sabbah, D. A., Hajjo, R., Bardaweel, S. K., & Zhong, H. A. (2021) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1924150 · Cited by 52 · see citing works
Developing biomarker-specific end points in lung cancer clinical trials
Neal, J. W., Gainor, J. F., & Shaw, A. T. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.222 · Cited by 51 · see citing works
Pharmacodynamic Biomarkers: Falling Short of the Mark?
Gainor, J. F., Longo, D. L., & Chabner, B. A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3132 · Cited by 49 · see citing works
PI3K/AKT/mTOR pathway inhibitors: the ideal combination partners for breast cancer therapies?
Abraham, J. (2014) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.2015.961429 · Cited by 46 · see citing works
Improving chemoradiation efficacy by PI3-K/AKT inhibition
Stegeman, H., Span, P. N., Kaanders, J. H. A. M., & Bussink, J. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.09.005 · Cited by 46 · see citing works
Pharmacodynamic Biomarker Development for PI3K Pathway Therapeutics
Josephs, D. H., & Sarker, D. (2015) · Translational Oncogenomics · doi:10.4137/tog.s30529 · Cited by 46 · see citing works
PI3K inhibition to overcome endocrine resistance in breast cancer
Keegan, N. M., Gleeson, J. P., Hennessy, B. T., & Morris, P. G. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1417384 · Cited by 46 · see citing works
Proline-rich AKT substrate of 40-kDa (PRAS40) in the pathophysiology of cancer
Malla, R., Ashby, C. R., Narayanan, N. K., Narayanan, B. A., Faridi, J. S., & Tiwari, A. K. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.05.041 · Cited by 46 · see citing works
Targeting the RAS upstream and downstream signaling pathway for cancer treatment
Hossain, M. A. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176727 · Cited by 47 · see citing works
TAK-228 (formerly MLN0128), an investigational dual TORC1/2 inhibitor plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies
Burris, H. A., Kurkjian, C. D., Hart, L., Pant, S., Murphy, P. B., Jones, S. F., Neuwirth, R. B., Patel, C. G., Zohren, F., & Infante, J. R. (2017) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-017-3343-4 · Cited by 45 · see citing works
Structure-Based Drug Design and Synthesis of PI3Kα-Selective Inhibitor (PF-06843195)
Cheng, H., Orr, S. T. M., Bailey, S., Brooun, A., Chen, P., Deal, J. G., Deng, Y., Edwards, M. P., Gallego, G. M., Grodsky, N. B., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01652 · Cited by 45 · see citing works
Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component
Thibault, B., Ramos‐Delgado, F., Tostivint, E. P., Therville, N., Cintas, C., Arcucci, S., Cassant‐Sourdy, S., Reyes‐Castellanos, G., Tosolini, M., Villard, A. V., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013502 · Cited by 44 · see citing works
Update on the Treatment of Metastatic Squamous Non-Small Cell Lung Cancer in New Era of Personalized Medicine
Soldera, S. V., & Leighl, N. B. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00050 · Cited by 44 · see citing works
Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)
Huang, X., You, L., Nepovimová, E., Psotka, M., Maliňák, D., Valko, M., Sivák, L., Korábečný, J., Heger, Z., Adam, V., et al. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2023.2237209 · Cited by 42 · see citing works
A Randomized, Phase II Trial of Cetuximab With or Without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients With Metastatic Colorectal Carcinoma.
Bowles, D. W., Kochenderfer, M., Cohn, A., Sideris, L., Nguyen, N., Cline-Burkhardt, V., Schnadig, I., Choi, M., Nabell, L., Chaudhry, A., et al. (2016) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2016.03.004 · Cited by 42 · see citing works
PI3K-targeting strategy using alpelisib to enhance the antitumor effect of paclitaxel in human gastric cancer
Kim, K., Kim, J., Sung, J. H., Suh, K. J., Lee, J. Y., Kim, S. H., Lee, J., Kim, J. W., Kim, Y. J., Kim, J. H., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-68998-w · Cited by 40 · see citing works
Phase I/II dose-escalation study of PI3K inhibitors pilaralisib or voxtalisib in combination with letrozole in patients with hormone-receptor-positive and HER2-negative metastatic breast cancer refractory to a non-steroidal aromatase inhibitor
Blackwell, K., Burris, H. A., Gómez, P., Henry, N. L., Isakoff, S. J., Campana, F., Gao, L., Jiang, J., Macé, S., & Tolaney, S. M. (2015) · Breast Cancer Research and Treatment · doi:10.1007/s10549-015-3615-9 · Cited by 37 · see citing works
First‐in‐human trial of the PI3Kβ‐selective inhibitor SAR260301 in patients with advanced solid tumors
Bedard, P. L., Davies, M. A., Kopetz, S., Juric, D., Shapiro, G. I., Luke, J. J., Spreafico, A., Wu, B., Castell, C., Gomez, C., et al. (2017) · Cancer · doi:10.1002/cncr.31044 · Cited by 37 · see citing works
Self-citation
La voie de signalisation PI3K-AKT-mTOR : description, développement thérapeutique, résistances, marqueurs prédictifs/pronostiques et applications thérapeutiques en cancérologie
Brotelle, T., & Bay, J. (2015) · Bulletin du Cancer · doi:10.1016/j.bulcan.2015.09.011 · Cited by 36 · see citing works
Discovery of a Novel Series of 7-Azaindole Scaffold Derivatives as PI3K Inhibitors with Potent Activity
Yang, C., Zhang, X., Wang, Y., Yang, Y., Liu, X., Deng, M., Yu, J., Ling, Y., Meng, L., & Zhou, Y. (2017) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.7b00222 · Cited by 35 · see citing works
ERK-dependent IL-6 autocrine signaling mediates adaptive resistance to pan-PI3K inhibitor BKM120 in head and neck squamous cell carcinoma
Yun, M. R., Choi, H., Kang, H., Lee, Y., Joo, H., Kim, D. H., Kim, H. R., Hong, M. H., Yoon, S. O., & Cho, B. C. (2017) · Oncogene · doi:10.1038/onc.2017.339 · Cited by 35 · see citing works
Complications of hyperglycaemia with PI3K–AKT–mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials
Geuna, E., Roda, D., Rafii, S., Jiménez, B., Capelán, M., Rihawi, K., Montemurro, F., Yap, T. A., Kaye, S. B., Bono, J. S. D., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.373 · Cited by 33 · see citing works
Novel PI3K/Akt/mTOR pathway inhibitors plus radiotherapy: Strategy for non-small cell lung cancer with mutant RAS gene
Chen, K., Shang, Z., Dai, A.-L., & Dai, P.-L. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117816 · Cited by 33 · see citing works
The Role of Genomics and Proteomics in Lung Cancer Early Detection and Treatment
Abbasian, M. H., Ardekani, A. M., Sobhani, N., & Roudi, R. (2022) · Cancers · doi:10.3390/cancers14205144 · Cited by 33 · see citing works
Medication-induced hyperglycemia and diabetes mellitus: a review of current literature and practical management strategies
Jain, A. B., & Lai, V. (2024) · Diabetes Therapy · doi:10.1007/s13300-024-01628-0 · Cited by 32 · see citing works
Phase Ia/Ib study of the pan-class I PI3K inhibitor pictilisib (GDC-0941) administered as a single agent in Japanese patients with solid tumors and in combination in Japanese patients with non-squamous non-small cell lung cancer
Yamamoto, N., Fujiwara, Y., Tamura, K., Kondo, S., Iwasa, S., Tanabe, Y., Horiike, A., Yanagitani, N., Kitazono, S., Inatani, M., et al. (2016) · Investigational New Drugs · doi:10.1007/s10637-016-0382-3 · Cited by 30 · see citing works
Phase I Dose-Escalation Study of Pilaralisib (SAR245408, XL147) in Combination with Paclitaxel and Carboplatin in Patients with Solid Tumors
Wheler, J. J., Mutch, D. G., Lager, J. J., Castell, C., Liu, L., Jiang, J., & Traynor, A. M. (2017) · The Oncologist · doi:10.1634/theoncologist.2016-0257 · Cited by 30 · see citing works
Prediction of active human dose: learnings from 20 years of Merck KGaA experience, illustrated by case studies
Peters, S. A., Petersson, C., Blaukat, A., Halle, J.-P., & Dolgos, H. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.01.002 · Cited by 28 · see citing works
Phase Ib Study of Safety and Pharmacokinetics of the PI3K Inhibitor SAR245408 with the HER3-Neutralizing Human Antibody SAR256212 in Patients with Solid Tumors
Abramson, V. G., Supko, J. G., Ballinger, T. J., Cleary, J. M., Hilton, J. F., Tolaney, S. M., Chau, N. G., Cho, D. C., Pearlberg, J., Lager, J. J., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1764 · Cited by 29 · see citing works
Self-citation
Nanomicellar TGX221 blocks xenograft tumor growth of prostate cancer in nude mice
Chen, R., Zhao, Y., Huang, Y., Yang, Q., Zeng, X., Jiang, W., Liu, J., Thrasher, J. B., Forrest, M. L., & Li, B. (2015) · The Prostate · doi:10.1002/pros.22941 · Cited by 28 · see citing works
Cross Talk Networks of Mammalian Target of Rapamycin Signaling With the Ubiquitin Proteasome System and Their Clinical Implications in Multiple Myeloma
Eichner, R., Fernández‐Sáiz, V., Targosz, B., & Bassermann, F. C. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.06.001 · Cited by 27 · see citing works
Driver mutation characteristics of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in advanced non-small cell lung cancer
Daher, S., Zer, A., Tschernichovsky, R., Yacobi, R., Barshack, I., Tsabari, S., Rottenberg, Y., Zick, A., Gottfried, T., Lobachov, A., et al. (2023) · Lung Cancer · doi:10.1016/j.lungcan.2023.02.023 · Cited by 27 · see citing works
Design and Synthesis of 1,3,5-Triazines or Pyrimidines Containing Dithiocarbamate Moiety as PI3Kα Selective Inhibitors
Tang, J., Liu, J., He, X., Fu, S., Wang, K., Li, C., Li, Y., Zhu, Y., Gong, P., Zhao, Y., et al. (2023) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.3c00287 · Cited by 26 · see citing works
Targeting PIK3CA Alterations in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2–Negative Advanced Breast Cancer: New Therapeutic Approaches and Practical Considerations
Schwartzberg, L. S., & Vidal, G. A. (2020) · Clinical Breast Cancer · doi:10.1016/j.clbc.2020.02.002 · Cited by 26 · see citing works
IQGAP3 Overexpression Correlates With Poor Prognosis and Radiation Therapy Resistance in Breast Cancer
Hua, X., Long, Z., Zhang, W.-W., Lin, C., Sun, X., Wen, W., Lu, Z.-J., Guo, N., He, Z.-Y., Bing-Song, L., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.584450 · Cited by 26 · see citing works
Novel 2-(2-alkylthiobenzenesulfonyl)-3-(phenylprop-2-ynylideneamino)guanidine derivatives as potent anticancer agents – Synthesis, molecular structure, QSAR studies and metabolic stability
Pogorzelska, A., Slawinski, J. J., Żołnowska, B., Szafrański, K., Kawiak, A., Chojnacki, J., Ulenberg, S., Zielińska, J., & Bączek, T. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.06.059 · Cited by 22 · see citing works
For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors
Buchanan, C. M., Lee, K., & Shepherd, P. R. (2019) · Biomolecules · doi:10.3390/biom9090402 · Cited by 22 · see citing works
Suppression of mTOR pathway in solid tumors: lessons learned from clinical experience in renal cell carcinoma and neuroendocrine tumors and new perspectives
Ortolani, S., Ciccarese, C., Cingarlini, S., Tortora, G., & Massari, F. (2015) · Future Oncology · doi:10.2217/fon.15.81 · Cited by 22 · see citing works

Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of SAR245409 (XL765), a Novel, Orally Administered PI3K/mTOR Inhibitor in Patients with Advanced Solid Tumors
Papadopoulos, K. P., Tabernero, J. M., Markman, B., Patnaik, A., Tolcher, A. W., Baselga, J. M., Shi, W., Égile, C., Ruiz-Soto, R., Laird, A., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2403 · Cited by 96 · see citing works
Self-citation
Phase I Safety and Pharmacokinetic Study of the PI3K/mTOR Inhibitor SAR245409 (XL765) in Combination with Erlotinib in Patients with Advanced Solid Tumors
Janne, P. A., Cohen, R. B., Laird, A., Macé, S., Engelman, J. A., Ruiz-Soto, R., Rockich, K. T., Xu, J., Shapiro, G. I., Martínez, P., et al. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000088 · Cited by 48 · see citing works
Self-citation
A phase I dose-escalation study of XL147 (SAR245408), a PI3K inhibitor administered orally to patients (pts) with advanced malignancies.
Edelman, G. M., Bedell, C., Shapiro, G. I., Pandya, S. S., Kwak, E. L., Scheffold, C., Nguyen, L. T., Laird, A., Baselga, J. M., & Rodon, J. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.3004 · Cited by 77 · see citing works
Self-citation
Phase I Trial of SAR245408 (S08), a Pan-Phosphatidylinositol 3 Kinase (PI3K) Inhibitor, in Patients with Chronic Lymphocytic Leukemia (CLL) and Lymphoma
Brown, J. R., Davids, M. S., Rodon, J. A., Abrisqueta, P., DeCillis, A. P., Rockich, K. T., Égile, C., Kelly, A., Xu, Y., Lager, J. J., et al. (2011) · Blood · doi:10.1182/blood.v118.21.2683.2683 · Cited by 11 · see citing works
Self-citation
First-in-human phase I trial of the PI3Kb-selective inhibitor SAR260301 in patients with advanced solid tumors (NCT01673737).
Bedard, P. L., Davies, M. A., Kopetz, S., Flaherty, K. T., Shapiro, G. I., Luke, J. J., Spreafico, A., Wu, B., Gomez, C., Cartot‐Cotton, S., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.2564 · Cited by 8 · see citing works
Self-citation

Authors: Shapiro, G. I., Rodon, J., Bedell, C., Kwak, E. L., Baselga, J., Braña, I., Pandya, S. S., Scheffold, C., Laird, A. D., Nguyen, L. T., Xu, Y., Egile, C., & Edelman, G.
Affiliations: Beth Israel Deaconess Medical Center (US)
Authors' Affiliations: 1Dana-Farber Cancer Institute; 2Massachusetts General Hospital; 3Beth Israel Deaconess Medical Center, Boston, Massachusetts; 4Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; 5Mary Crowley Cancer Research Centers, Dallas, Texas; 6Exelixis Inc., South San Francisco, California; and 7Sanofi, Cambridge, Massachusetts, and Vitry-sur-Seine, France
ORCID: Shapiro, Geoffrey I.
Rodon, Jordi
Baselga, Jose
Braña, Irene
Laird, A. Douglas
Nguyen, Linh T.
Xu, Yi
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2014-01-01
Volume: 20
Issue: 1
Pages: 233-245
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-13-1777
OpenAlex: W1979937839
Cited by: 152
References: 28
Citations by year: 2025: 1 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 24 · 2016: 21 · 2015: 28 · 2014: 24
FWCI: 10.89
Type: journal article
Language: en
Open access: closed
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: phosphatidylinositol 3-kinase, maximum tolerated dose, dose-limiting toxicity, maculopapular rash, pharmacokinetics, pharmacodynamics, Akt phosphorylation, advanced solid tumors, non-small cell lung cancer, dose proportionality, tumor biopsy
MeSH terms: Phosphoinositide-3 Kinase Inhibitors, Administration, Oral, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Dose-Response Relationship, Drug, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Quinoxalines, Skin Diseases, Sulfonamides, Signal Transduction, Treatment Outcome, Area Under Curve, Maximum Tolerated Dose, Phosphatidylinositol 3-Kinase

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Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of SAR245408 (XL147), an Oral Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors

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