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35 results on '"Aronchik, Ida"'

1. BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas

Author

Moreno, Victor, Vieito, Maria, Sepulveda, Juan Manuel, Galvao, Vladimir, Hernández-Guerrero, Tatiana, Doger, Bernard, Saavedra, Omar, Carlo-Stella, Carmelo, Michot, Jean-Marie, Italiano, Antoine, Magagnoli, Massimo, Carpio, Cecilia, Pinto, Antonio, Sarmiento, Rafael, Amoroso, Barbara, Aronchik, Ida, Filvaroff, Ellen, Hanna, Bishoy, Wei, Xin, Nikolova, Zariana, and Braña, Irene

Published
2023
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3. Supplementary Table S8 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Author

Jiang, Jingjing, primary, Jiang, Lingyan, primary, Maldonato, Benjamin J., primary, Wang, Yingyun, primary, Holderfield, Matthew, primary, Aronchik, Ida, primary, Winters, Ian P., primary, Salman, Zeena, primary, Blaj, Cristina, primary, Menard, Marie, primary, Brodbeck, Jens, primary, Chen, Zhe, primary, Wei, Xing, primary, Rosen, Michael J., primary, Gindin, Yevgeniy, primary, Lee, Bianca J., primary, Evans, James W., primary, Chang, Stephanie, primary, Wang, Zhican, primary, Seamon, Kyle J., primary, Parsons, Dylan, primary, Cregg, James, primary, Marquez, Abby, primary, Tomlinson, Aidan C.A., primary, Yano, Jason K., primary, Knox, John E., primary, Quintana, Elsa, primary, Aguirre, Andrew J., primary, Arbour, Kathryn C., primary, Reed, Abby, primary, Gustafson, W. Clay, primary, Gill, Adrian L., primary, Koltun, Elena S., primary, Wildes, David, primary, Smith, Jacqueline A.M., primary, Wang, Zhengping, primary, and Singh, Mallika, primary

Published
2024
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4. Supplementary Figure S1-S6 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Author

Jiang, Jingjing, primary, Jiang, Lingyan, primary, Maldonato, Benjamin J., primary, Wang, Yingyun, primary, Holderfield, Matthew, primary, Aronchik, Ida, primary, Winters, Ian P., primary, Salman, Zeena, primary, Blaj, Cristina, primary, Menard, Marie, primary, Brodbeck, Jens, primary, Chen, Zhe, primary, Wei, Xing, primary, Rosen, Michael J., primary, Gindin, Yevgeniy, primary, Lee, Bianca J., primary, Evans, James W., primary, Chang, Stephanie, primary, Wang, Zhican, primary, Seamon, Kyle J., primary, Parsons, Dylan, primary, Cregg, James, primary, Marquez, Abby, primary, Tomlinson, Aidan C.A., primary, Yano, Jason K., primary, Knox, John E., primary, Quintana, Elsa, primary, Aguirre, Andrew J., primary, Arbour, Kathryn C., primary, Reed, Abby, primary, Gustafson, W. Clay, primary, Gill, Adrian L., primary, Koltun, Elena S., primary, Wildes, David, primary, Smith, Jacqueline A.M., primary, Wang, Zhengping, primary, and Singh, Mallika, primary

Published
2024
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5. Supplementary Method from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Author

Jiang, Jingjing, primary, Jiang, Lingyan, primary, Maldonato, Benjamin J., primary, Wang, Yingyun, primary, Holderfield, Matthew, primary, Aronchik, Ida, primary, Winters, Ian P., primary, Salman, Zeena, primary, Blaj, Cristina, primary, Menard, Marie, primary, Brodbeck, Jens, primary, Chen, Zhe, primary, Wei, Xing, primary, Rosen, Michael J., primary, Gindin, Yevgeniy, primary, Lee, Bianca J., primary, Evans, James W., primary, Chang, Stephanie, primary, Wang, Zhican, primary, Seamon, Kyle J., primary, Parsons, Dylan, primary, Cregg, James, primary, Marquez, Abby, primary, Tomlinson, Aidan C.A., primary, Yano, Jason K., primary, Knox, John E., primary, Quintana, Elsa, primary, Aguirre, Andrew J., primary, Arbour, Kathryn C., primary, Reed, Abby, primary, Gustafson, W. Clay, primary, Gill, Adrian L., primary, Koltun, Elena S., primary, Wildes, David, primary, Smith, Jacqueline A.M., primary, Wang, Zhengping, primary, and Singh, Mallika, primary

Published
2024
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6. Data from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Author

Jiang, Jingjing, primary, Jiang, Lingyan, primary, Maldonato, Benjamin J., primary, Wang, Yingyun, primary, Holderfield, Matthew, primary, Aronchik, Ida, primary, Winters, Ian P., primary, Salman, Zeena, primary, Blaj, Cristina, primary, Menard, Marie, primary, Brodbeck, Jens, primary, Chen, Zhe, primary, Wei, Xing, primary, Rosen, Michael J., primary, Gindin, Yevgeniy, primary, Lee, Bianca J., primary, Evans, James W., primary, Chang, Stephanie, primary, Wang, Zhican, primary, Seamon, Kyle J., primary, Parsons, Dylan, primary, Cregg, James, primary, Marquez, Abby, primary, Tomlinson, Aidan C.A., primary, Yano, Jason K., primary, Knox, John E., primary, Quintana, Elsa, primary, Aguirre, Andrew J., primary, Arbour, Kathryn C., primary, Reed, Abby, primary, Gustafson, W. Clay, primary, Gill, Adrian L., primary, Koltun, Elena S., primary, Wildes, David, primary, Smith, Jacqueline A.M., primary, Wang, Zhengping, primary, and Singh, Mallika, primary

Published
2024
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7. Abstract B080: Mutant-selective KRASG12D(ON) inhibitor suppresses proliferation in vitro and tumor growth in vivo of KrasG12D GEMM-derived PDAC organoids

Author

Labrecque, Mark P., primary, Jiang, Lingyan, additional, Nasholm, Nicole, additional, Nayak, Biswadeep, additional, Yu, Xinxing, additional, Song, Avian, additional, Weller, Caroline, additional, Evans, James W., additional, Zafra, Maria Paz, additional, Parsons, Marie, additional, Menard, Marie, additional, Dow, Lukas E., additional, Jiang, Jingjing, additional, Aronchik, Ida, additional, and Singh, Mallika, additional

Published
2024
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8. Cooperative antiproliferative signaling by aspirin and indole-3-carbinol targets microphthalmia-associated transcription factor gene expression and promoter activity in human melanoma cells

Author

Poindexter, Kevin M, Matthew, Susanne, Aronchik, Ida, and Firestone, Gary L

Subjects
Biochemistry and Cell Biology, Biological Sciences, Human Genome, Genetics, Cancer, Aetiology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Aspirin, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Down-Regulation, Drug Synergism, Gene Expression, Humans, Indoles, Melanoma, Microphthalmia-Associated Transcription Factor, Promoter Regions, Genetic, Signal Transduction, Wnt Signaling Pathway, Indole-3-carbinol, LEF1, Melanoma cells, Microphthalmia-associated transcription factor, Wnt signaling, Toxicology, Biochemistry and cell biology
Abstract

Antiproliferative signaling of combinations of the nonsteroidal anti-inflammatory drug acetylsalicylic acid (aspirin) and indole-3-carbinol (I3C), a natural indolecarbinol compound derived from cruciferous vegetables, was investigated in human melanoma cells. Melanoma cell lines with distinct mutational profiles were sensitive to different extents to the antiproliferative response of aspirin, with oncogenic BRAF-expressing G361 cells and wild-type BRAF-expressing SK-MEL-30 cells being the most responsive. I3C triggered a strong proliferative arrest of G361 melanoma cells and caused only a modest decrease in the proliferation of SK-MEL-30 cells. In both cell lines, combinations of aspirin and I3C cooperatively arrested cell proliferation and induced a G1 cell cycle arrest, and nearly ablated protein and transcript levels of the melanocyte master regulator microphthalmia-associated transcription factor isoform M (MITF-M). In melanoma cells transfected with a -333/+120-bp MITF-M promoter-luciferase reporter plasmid, treatment with aspirin and I3C cooperatively disrupted MITF-M promoter activity, which accounted for the loss of MITF-M gene products. Mutational analysis revealed that the aspirin required the LEF1 binding site, whereas I3C required the BRN2 binding site to mediate their combined and individual effects on MITF-M promoter activity. Consistent with LEF1 being a downstream effector of Wnt signaling, aspirin, but not I3C, downregulated protein levels of the Wnt co-receptor LDL receptor-related protein-6 and β-catenin and upregulated the β-catenin destruction complex component Axin. Taken together, our results demonstrate that aspirin-regulated Wnt signaling and I3C-targeted signaling pathways converge at distinct DNA elements in the MITF-M promoter to cooperatively disrupt MITF-M expression and melanoma cell proliferation.

Published
2016

10. Abstract 526: RMC-9805, a first-in-class, mutant-selective, covalent and oral KRASG12D(ON) inhibitor that induces apoptosis and drives tumor regression in preclinical models of KRASG12D cancers

Author

Jiang, Lingyan, primary, Menard, Marie, additional, Weller, Caroline, additional, Wang, Zhican, additional, Burnett, Les, additional, Aronchik, Ida, additional, Steele, Shelby, additional, Flagella, Mike, additional, Zhao, Ruiping, additional, Evans, James W W., additional, Chin, Shook, additional, Chou, Kang-Jye, additional, Mu, Yunming, additional, Longhi, Michael, additional, McDowell, Laura, additional, Knox, John E., additional, Gill, Adrian, additional, Smith, Jacqueline A., additional, Singh, Mallika, additional, Quintana, Elsa, additional, and Jiang, Jingjing, additional

Published
2023
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11. Supplementary Tables and Figures from Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance

Author

Aronchik, Ida, primary, Dai, Yumin, primary, Labenski, Matt, primary, Barnes, Carmen, primary, Jones, Terri, primary, Qiao, Lixin, primary, Beebe, Lisa, primary, Malek, Mehnaz, primary, Elis, Winfried, primary, Shi, Tao, primary, Mavrommatis, Konstantinos, primary, Bray, Gordon L., primary, and Filvaroff, Ellen H., primary

Published
2023
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12. Supplementary figure legends and supplementary methods from Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance

Author

Aronchik, Ida, primary, Dai, Yumin, primary, Labenski, Matt, primary, Barnes, Carmen, primary, Jones, Terri, primary, Qiao, Lixin, primary, Beebe, Lisa, primary, Malek, Mehnaz, primary, Elis, Winfried, primary, Shi, Tao, primary, Mavrommatis, Konstantinos, primary, Bray, Gordon L., primary, and Filvaroff, Ellen H., primary

Published
2023
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13. Supplementary Figures 1 - 4 from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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14. Data from Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance

Author

Aronchik, Ida, primary, Dai, Yumin, primary, Labenski, Matt, primary, Barnes, Carmen, primary, Jones, Terri, primary, Qiao, Lixin, primary, Beebe, Lisa, primary, Malek, Mehnaz, primary, Elis, Winfried, primary, Shi, Tao, primary, Mavrommatis, Konstantinos, primary, Bray, Gordon L., primary, and Filvaroff, Ellen H., primary

Published
2023
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15. Supplementary Methods from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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16. Supplementary Table 2 from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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17. Supplementary Table 1 from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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18. Supplementary Figure Legends from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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19. Supplementary Data from Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

Author

Hollebecque, Antoine, primary, Salvagni, Stefania, primary, Plummer, Ruth, primary, Isambert, Nicolas, primary, Niccoli, Patricia, primary, Capdevila, Jaume, primary, Curigliano, Giuseppe, primary, Moreno, Victor, primary, Martin-Romano, Patricia, primary, Baudin, Eric, primary, Arias, Marina, primary, Mora, Sheila, primary, de Alvaro, Juan, primary, Di Martino, Jorge, primary, Parra-Palau, Josep L., primary, Sánchez-Pérez, Tania, primary, Aronchik, Ida, primary, Filvaroff, Ellen H., primary, Lamba, Manisha, primary, Nikolova, Zariana, primary, and de Bono, Johann S., primary

Published
2023
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20. Supplementary Figure S1 from Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

Author

Hollebecque, Antoine, primary, Salvagni, Stefania, primary, Plummer, Ruth, primary, Isambert, Nicolas, primary, Niccoli, Patricia, primary, Capdevila, Jaume, primary, Curigliano, Giuseppe, primary, Moreno, Victor, primary, Martin-Romano, Patricia, primary, Baudin, Eric, primary, Arias, Marina, primary, Mora, Sheila, primary, de Alvaro, Juan, primary, Di Martino, Jorge, primary, Parra-Palau, Josep L., primary, Sánchez-Pérez, Tania, primary, Aronchik, Ida, primary, Filvaroff, Ellen H., primary, Lamba, Manisha, primary, Nikolova, Zariana, primary, and de Bono, Johann S., primary

Published
2023
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23. Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, “window-of-opportunity” study

Author

Moreno, Victor, primary, Manuel Sepúlveda, Juan, additional, Reardon, David A, additional, Pérez-Núñez, Ángel, additional, González León, Pedro, additional, Hanna, Bishoy, additional, Filvaroff, Ellen, additional, Aronchik, Ida, additional, Chang, Henry, additional, Amoroso, Barbara, additional, Zuraek, Marlene, additional, Sanchez-Perez, Tania, additional, Mendez, Cristina, additional, Stephens, Daniel, additional, Nikolova, Zariana, additional, and Vogelbaum, Michael A, additional

Published
2022
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24. Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma

Author

Vieito, Maria, Simonelli, Matteo, De Vos, Filip, Moreno, Victor, Geurts, Marjolein, Lorenzi, Elena, Macchini, Marina, Van Den Bent, Martin J., Del Conte, Gianluca, De Jonge, Maja, Martín-Soberón, Maria Cruz, Amoroso, Barbara, Sanchez-Perez, Tania, Zuraek, Marlene, Hanna, Bishoy, Aronchik, Ida, Filvaroff, Ellen, Chang, Henry, Mendez, Cristina, Arias Parro, Marina, Wei, Xin, Nikolova, Zariana, Sepulveda, Juan Manuel, Vieito, Maria, Simonelli, Matteo, De Vos, Filip, Moreno, Victor, Geurts, Marjolein, Lorenzi, Elena, Macchini, Marina, Van Den Bent, Martin J., Del Conte, Gianluca, De Jonge, Maja, Martín-Soberón, Maria Cruz, Amoroso, Barbara, Sanchez-Perez, Tania, Zuraek, Marlene, Hanna, Bishoy, Aronchik, Ida, Filvaroff, Ellen, Chang, Henry, Mendez, Cristina, Arias Parro, Marina, Wei, Xin, Nikolova, Zariana, and Sepulveda, Juan Manuel

Abstract

Background: Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas. Methods: In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint. Results: The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate. Trotabresib pharmacokinetics and pharmacodynamics in both settings were consistent with previous data for trotabresib monotherapy. The RP2D of trotabresib was selected as 30 mg 4 days on/24 days off in both settings. At last follow-up, 5 (28%) and 6 (43%) patients remain on treatment in the adjuvant and concomitant settings, respectively, with 1 patient in the adjuvant cohort achieving complete response. Conclusions: Trotabresib combined with TMZ in the adjuvant setting and with TMZ+RT in the concomitant setting was safe and well tolerated in patients with ndGBM, with encouraging treatment durations. Trotabresib 30 mg was established as the RP2D in both settings.

Published
2022

25. Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma

Author

MS Medische Oncologie, Cancer, Vieito, Maria, Simonelli, Matteo, de Vos, Filip, Moreno, Victor, Geurts, Marjolein, Lorenzi, Elena, Macchini, Marina, van den Bent, Martin J, Del Conte, Gianluca, de Jonge, Maja, Martín-Soberón, Maria Cruz, Amoroso, Barbara, Sanchez-Perez, Tania, Zuraek, Marlene, Hanna, Bishoy, Aronchik, Ida, Filvaroff, Ellen, Chang, Henry, Mendez, Cristina, Arias Parro, Marina, Wei, Xin, Nikolova, Zariana, Sepulveda, Juan Manuel, MS Medische Oncologie, Cancer, Vieito, Maria, Simonelli, Matteo, de Vos, Filip, Moreno, Victor, Geurts, Marjolein, Lorenzi, Elena, Macchini, Marina, van den Bent, Martin J, Del Conte, Gianluca, de Jonge, Maja, Martín-Soberón, Maria Cruz, Amoroso, Barbara, Sanchez-Perez, Tania, Zuraek, Marlene, Hanna, Bishoy, Aronchik, Ida, Filvaroff, Ellen, Chang, Henry, Mendez, Cristina, Arias Parro, Marina, Wei, Xin, Nikolova, Zariana, and Sepulveda, Juan Manuel

Published
2022

26. Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, "window-of-opportunity" study.

Author

Moreno, Victor, Sepúlveda, Juan Manuel, Reardon, David A, Pérez-Núñez, Ángel, León, Pedro González, Hanna, Bishoy, Filvaroff, Ellen, Aronchik, Ida, Chang, Henry, Amoroso, Barbara, Zuraek, Marlene, Sanchez-Perez, Tania, Mendez, Cristina, Stephens, Daniel, Nikolova, Zariana, and Vogelbaum, Michael A

Published
2023
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27. Clinical activity of CC‐90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies

Author

Hollebecque, Antoine, primary, Salvagni, Stefania, additional, Plummer, Ruth, additional, Niccoli, Patricia, additional, Capdevila, Jaume, additional, Curigliano, Giuseppe, additional, Moreno, Victor, additional, de Braud, Filippo, additional, de Villambrosia, Sonia Gonzalez, additional, Martin‐Romano, Patricia, additional, Baudin, Eric, additional, Arias, Marina, additional, de Alvaro, Juan, additional, Parra‐Palau, Josep L., additional, Sánchez‐Pérez, Tania, additional, Aronchik, Ida, additional, Filvaroff, Ellen H., additional, Lamba, Manisha, additional, Nikolova, Zariana, additional, and de Bono, Johann S., additional

Published
2022
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28. Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma

Author

Vieito, Maria, primary, Simonelli, Matteo, additional, de Vos, Filip, additional, Moreno, Victor, additional, Geurts, Marjolein, additional, Lorenzi, Elena, additional, Macchini, Marina, additional, van den Bent, Martin J, additional, Del Conte, Gianluca, additional, de Jonge, Maja, additional, Martín-Soberón, Maria Cruz, additional, Amoroso, Barbara, additional, Sanchez-Perez, Tania, additional, Zuraek, Marlene, additional, Hanna, Bishoy, additional, Aronchik, Ida, additional, Filvaroff, Ellen, additional, Chang, Henry, additional, Mendez, Cristina, additional, Arias Parro, Marina, additional, Wei, Xin, additional, Nikolova, Zariana, additional, and Sepulveda, Juan Manuel, additional

Published
2022
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29. CTNI-16. TROTABRESIB (CC-90010, BMS-986378), A REVERSIBLE, POTENT ORAL BROMODOMAIN AND EXTRATERMINAL INHIBITOR (BETi) IN PATIENTS WITH HIGH-GRADE GLIOMAS: A PHASE 1 OPEN-LABEL ‘WINDOW OF OPPORTUNITY’ STUDY

Author

Vogelbaum, Michael, primary, Sepulveda, Juan Manuel, additional, Reardon, David, additional, Hanna, Bishoy, additional, Filvaroff, Ellen, additional, Aronchik, Ida, additional, Amoroso, Barbara, additional, Zuraek, Marlene, additional, Sanchez-Perez, Tania, additional, Mendez, Cristina, additional, Nikolova, Zariana, additional, and Moreno, Victor, additional

Published
2021
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30. CTNI-51. ADJUVANT TROTABRESIB, A REVERSIBLE POTENT BROMODOMAIN AND EXTRATERMINAL INHIBITOR, PLUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: INTERIM RESULTS FROM A PHASE 1B DOSE-FINDING STUDY

Author

Vieito, Maria, primary, Simonelli, Matteo, additional, de Vos, Filip, additional, Moreno, Victor, additional, Geurts, Marjolein, additional, Lorenzi, Elena, additional, Macchini, Marina, additional, van den Bent, Martin, additional, Del Conte, Gianluca, additional, de Jonge, Maja, additional, Amoroso, Barbara, additional, Sanchez-Perez, Tania, additional, Zuraek, Marlene, additional, Hanna, Bishoy, additional, Aronchik, Ida, additional, Filvaroff, Ellen, additional, Mendez, Cristina, additional, Wei, Xin, additional, Nikolova, Zariana, additional, and Sepulveda, Juan Manuel, additional

Published
2021
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31. Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

Author

Hollebecque, Antoine, primary, Salvagni, Stefania, additional, Plummer, Ruth, additional, Isambert, Nicolas, additional, Niccoli, Patricia, additional, Capdevila, Jaume, additional, Curigliano, Giuseppe, additional, Moreno, Victor, additional, Martin-Romano, Patricia, additional, Baudin, Eric, additional, Arias, Marina, additional, Mora, Sheila, additional, de Alvaro, Juan, additional, Di Martino, Jorge, additional, Parra-Palau, Josep L., additional, Sánchez-Pérez, Tania, additional, Aronchik, Ida, additional, Filvaroff, Ellen H., additional, Lamba, Manisha, additional, Nikolova, Zariana, additional, and de Bono, Johann S., additional

Published
2021
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32. Phase I study of CC-90010 in patients with advanced solid tumors and relapsed/refractory non-Hodgkin lymphoma (R/R NHL).

Author

Moreno, Victor, primary, Braña, Irene, additional, Sepulveda Sanchez, Juan Manuel Manuel, additional, Villar, Maria Vieito, additional, Hernandez-Guerrero, Tatiana, additional, Doger, Bernard, additional, Saavedra, Omar, additional, Ferrero, Olga, additional, Sarmiento, Rafael, additional, Arias, Marina, additional, De Alvaro, Juan, additional, DiMartino, Jorge F., additional, Zuraek, Marlene, additional, Sánchez Pérez, Tania, additional, Filvaroff, Ellen, additional, Aronchik, Ida, additional, Lamba, Manisha, additional, Hanna, Bishoy, additional, and Nikolova, Zariana G., additional

Published
2019
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33. Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance

Author

Aronchik, Ida, primary, Dai, Yumin, additional, Labenski, Matt, additional, Barnes, Carmen, additional, Jones, Terri, additional, Qiao, Lixin, additional, Beebe, Lisa, additional, Malek, Mehnaz, additional, Elis, Winfried, additional, Shi, Tao, additional, Mavrommatis, Konstantinos, additional, Bray, Gordon L., additional, and Filvaroff, Ellen H., additional

Published
2019
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34. A phase Ia study of CC-90003, a selective extracellular signal-regulated kinase (ERK) inhibitor, in patients with relapsed or refractory BRAF or RAS-mutant tumors.

Author

Mita, Monica M., primary, LoRusso, Patricia, additional, McArthur, Grant A., additional, Kim, Edward S., additional, Bray, Gordon L., additional, Hock, Nanette H, additional, Laille, Eric J., additional, Aronchik, Ida, additional, Filvaroff, Ellen, additional, Wu, Xiaoling, additional, and Bendell, Johanna C., additional

Published
2017
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35. Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers.

Author

Jiang J, Jiang L, Maldonato BJ, Wang Y, Holderfield M, Aronchik I, Winters IP, Salman Z, Blaj C, Menard M, Brodbeck J, Chen Z, Wei X, Rosen MJ, Gindin Y, Lee BJ, Evans JW, Chang S, Wang Z, Seamon KJ, Parsons D, Cregg J, Marquez A, Tomlinson ACA, Yano JK, Knox JE, Quintana E, Aguirre AJ, Arbour KC, Reed A, Gustafson WC, Gill AL, Koltun ES, Wildes D, Smith JAM, Wang Z, and Singh M

Subjects
Humans, Animals, Mice, Cell Line, Tumor, Proto-Oncogene Proteins p21(ras) genetics, Female, Antineoplastic Agents therapeutic use, Antineoplastic Agents pharmacology, Guanosine Triphosphate metabolism, Neoplasms drug therapy, Neoplasms genetics, Neoplasms metabolism, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms metabolism, Mutation, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Pancreatic Neoplasms metabolism, Male, Xenograft Model Antitumor Assays
Abstract

RAS-driven cancers comprise up to 30% of human cancers. RMC-6236 is a RAS(ON) multi-selective noncovalent inhibitor of the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms with broad therapeutic potential for the aforementioned unmet medical need. RMC-6236 exhibited potent anticancer activity across RAS-addicted cell lines, particularly those harboring mutations at codon 12 of KRAS. Notably, oral administration of RMC-6236 was tolerated in vivo and drove profound tumor regressions across multiple tumor types in a mouse clinical trial with KRASG12X xenograft models. Translational PK/efficacy and PK/PD modeling predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses, respectively, in patients with RAS-driven tumors. Consistent with this, we describe here objective responses in two patients (at 300 mg daily) with advanced KRASG12X lung and pancreatic adenocarcinoma, respectively, demonstrating the initial activity of RMC-6236 in an ongoing phase I/Ib clinical trial (NCT05379985)., Significance: The discovery of RMC-6236 enables the first-ever therapeutic evaluation of targeted and concurrent inhibition of canonical mutant and wild-type RAS-GTP in RAS-driven cancers. We demonstrate that broad-spectrum RAS-GTP inhibition is tolerable at exposures that induce profound tumor regressions in preclinical models of, and in patients with, such tumors. This article is featured in Selected Articles from This Issue, p. 897., (©2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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