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Start Over Author "Takebe A" Publisher american association for cancer research (aacr)
185 results on '"Takebe A"'

1. Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT

Author

Ahluwalia, Manmeet S., primary, Ozair, Ahmad, additional, Drappatz, Jan, additional, Ye, Xiaobu, additional, Peng, Sen, additional, Lee, Matthew, additional, Rath, Sanhita, additional, Dhruv, Harshil, additional, Hao, Yue, additional, Berens, Michael E., additional, Walbert, Tobias, additional, Holdhoff, Matthias, additional, Lesser, Glenn J., additional, Cloughesy, Timothy F., additional, Sloan, Andrew E., additional, Takebe, Naoko, additional, Couce, Marta, additional, Peereboom, David M., additional, Nabors, Burt, additional, Wen, Patrick Y., additional, Grossman, Stuart A., additional, and Rogers, Lisa R., additional

Published
2024
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2. Supplementary Material 1 from Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors

Author

Corcoran, Ryan B., primary, Do, Khanh T., primary, Kim, Jeong E., primary, Cleary, James M., primary, Parikh, Aparna R., primary, Yeku, Oladapo O., primary, Xiong, Niya, primary, Weekes, Colin D., primary, Veneris, Jennifer, primary, Ahronian, Leanne G., primary, Mauri, Gianluca, primary, Tian, Jun, primary, Norden, Bryanna L., primary, Michel, Alexa G., primary, Van Seventer, Emily E., primary, Siravegna, Giulia, primary, Camphausen, Kyle, primary, Chi, Gary, primary, Fetter, Isobel J., primary, Brugge, Joan S., primary, Chen, Helen, primary, Takebe, Naoko, primary, Penson, Richard T., primary, Juric, Dejan, primary, Flaherty, Keith T., primary, Sullivan, Ryan J., primary, Clark, Jeffrey W., primary, Heist, Rebecca S., primary, Matulonis, Ursula A., primary, Liu, Joyce F., primary, and Shapiro, Geoffrey I., primary

Published
2024
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3. FIGURE 3 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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4. Supplementary Table S1 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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5. Supplementary Figure S6 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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6. Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, additional, Kumar, Suresh, additional, Sun, Nai-Yun, additional, Elloumi, Fathi, additional, Thomas, Anish, additional, Roper, Nitin, additional, Varghese, Diana Grace, additional, Takebe, Naoko, additional, Zhang, Xiaohu, additional, Ceribelli, Michele, additional, Holland, David O., additional, Beck, Erin, additional, Itkin, Zina, additional, McKnight, Crystal, additional, Wilson, Kelli M., additional, Travers, Jameson, additional, Klumpp-Thomas, Carleen, additional, Thomas, Craig J., additional, Hoang, Chuong D., additional, Hernandez, Jonathan M., additional, Del Rivero, Jaydira, additional, and Pommier, Yves, additional

Published
2024
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7. FIGURE 6 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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8. FIGURE 5 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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9. FIGURE 4 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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10. FIGURE 8 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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11. FIGURE 7 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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12. FIGURE 2 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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13. FIGURE 1 from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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14. Data from Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts

Author

Arakawa, Yasuhiro, primary, Jo, Ukhyun, primary, Kumar, Suresh, primary, Sun, Nai-Yun, primary, Elloumi, Fathi, primary, Thomas, Anish, primary, Roper, Nitin, primary, Varghese, Diana Grace, primary, Takebe, Naoko, primary, Zhang, Xiaohu, primary, Ceribelli, Michele, primary, Holland, David O., primary, Beck, Erin, primary, Itkin, Zina, primary, McKnight, Crystal, primary, Wilson, Kelli M., primary, Travers, Jameson, primary, Klumpp-Thomas, Carleen, primary, Thomas, Craig J., primary, Hoang, Chuong D., primary, Hernandez, Jonathan M., primary, Del Rivero, Jaydira, primary, and Pommier, Yves, primary

Published
2024
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15. Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors

Author

Corcoran, Ryan B., primary, Do, Khanh T., additional, Kim, Jeong E., additional, Cleary, James M., additional, Parikh, Aparna R., additional, Yeku, Oladapo O., additional, Xiong, Niya, additional, Weekes, Colin D., additional, Veneris, Jennifer, additional, Ahronian, Leanne G., additional, Mauri, Gianluca, additional, Tian, Jun, additional, Norden, Bryanna L., additional, Michel, Alexa G., additional, Van Seventer, Emily E., additional, Siravegna, Giulia, additional, Camphausen, Kyle, additional, Chi, Gary, additional, Fetter, Isobel J., additional, Brugge, Joan S., additional, Chen, Helen, additional, Takebe, Naoko, additional, Penson, Richard T., additional, Juric, Dejan, additional, Flaherty, Keith T., additional, Sullivan, Ryan J., additional, Clark, Jeffrey W., additional, Heist, Rebecca S., additional, Matulonis, Ursula A., additional, Liu, Joyce F., additional, and Shapiro, Geoffrey I., additional

Published
2024
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16. Randomized Phase II Trial of Sunitinib or Cediranib in Alveolar Soft Part Sarcoma

Author

James Nguyen, Naoko Takebe, Shivaani Kummar, Albiruni Razak, Sant P. Chawla, Suzanne George, Shreyaskumar R. Patel, Mary Louise Keohan, Sujana Movva, Geraldine O'Sullivan Coyne, Khanh Do, Lamin Juwara, Brooke Augustine, Seth M. Steinberg, Laura Kuhlmann, S. Percy Ivy, James H. Doroshow, and Alice P. Chen

Subjects
Cancer Research, Oncology
Abstract

Purpose: Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor with few treatment options. We designed a phase II randomized trial to determine the activity and tolerability of single-agent cediranib or sunitinib in patients with advanced metastatic ASPS. Patients and Methods: Patients 16 years of age and older were randomized to receive cediranib (30 mg) or sunitinib (37.5 mg) in 28-day cycles. Patients could cross over to the other treatment arm at disease progression. The primary endpoint was to measure the objective response rate (ORR) for each agent. Median progression-free survival (mPFS) for the two arms was also determined. Results: Twenty-nine of 34 enrolled patients were evaluable for response. One patient on each of the initial two treatment arms had a partial response (ORR: 6.7% and 7.1% for cediranib and sunitinib, respectively). Twenty-four patients had a best response of stable disease (86.7% and 78.6% for cediranib and sunitinib, respectively). There were no significant differences in mPFS for the two treatment arms. Clinical benefit (i.e., objective response or stable disease for a minimum of four or six cycles of therapy) on the first-line tyrosine kinase inhibitor (TKI) therapy did not predict benefit on the second-line TKI. Both drugs were well tolerated. As of August 2021, 1 patient (unevaluable for ORR) remains on study. Conclusions: The study did not meet its endpoints for ORR. Although both TKIs provided clinical benefit, the outcomes may have been attenuated in patients who had progressed ≤6 months before enrollment, potentially accounting for the low response rates. See related commentary by Wilky and Maleddu, p. 1163

Published
2022
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17. Supplemental Figure S2 from Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use

Author

Srivastava, Apurva K., primary, Jaganathan, Soumya, primary, Stephen, Laurie, primary, Hollingshead, Melinda G., primary, Layhee, Adam, primary, Damour, Eric, primary, Govindharajulu, Jeevan Prasaad, primary, Donohue, Jennifer, primary, Esposito, Dominic, primary, Mapes, James P., primary, Kinders, Robert J., primary, Takebe, Naoko, primary, Tomaszewski, Joseph E., primary, Kummar, Shivaani, primary, Doroshow, James H., primary, and Parchment, Ralph E., primary

Published
2023
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18. Supplemental Table S2 from Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use

Author

Srivastava, Apurva K., primary, Jaganathan, Soumya, primary, Stephen, Laurie, primary, Hollingshead, Melinda G., primary, Layhee, Adam, primary, Damour, Eric, primary, Govindharajulu, Jeevan Prasaad, primary, Donohue, Jennifer, primary, Esposito, Dominic, primary, Mapes, James P., primary, Kinders, Robert J., primary, Takebe, Naoko, primary, Tomaszewski, Joseph E., primary, Kummar, Shivaani, primary, Doroshow, James H., primary, and Parchment, Ralph E., primary

Published
2023
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19. Supplemental Materials and Methods from Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use

Author

Srivastava, Apurva K., primary, Jaganathan, Soumya, primary, Stephen, Laurie, primary, Hollingshead, Melinda G., primary, Layhee, Adam, primary, Damour, Eric, primary, Govindharajulu, Jeevan Prasaad, primary, Donohue, Jennifer, primary, Esposito, Dominic, primary, Mapes, James P., primary, Kinders, Robert J., primary, Takebe, Naoko, primary, Tomaszewski, Joseph E., primary, Kummar, Shivaani, primary, Doroshow, James H., primary, and Parchment, Ralph E., primary

Published
2023
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20. Supplementary Tables 1 - 3 from Phase I Study of Vismodegib in Children with Recurrent or Refractory Medulloblastoma: A Pediatric Brain Tumor Consortium Study

Author

Gajjar, Amar, primary, Stewart, Clinton F., primary, Ellison, David W., primary, Kaste, Sue, primary, Kun, Larry E., primary, Packer, Roger J., primary, Goldman, Stewart, primary, Chintagumpala, Murali, primary, Wallace, Dana, primary, Takebe, Naoko, primary, Boyett, James M., primary, Gilbertson, Richard J., primary, and Curran, Tom, primary

Published
2023
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21. Data from Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors

Author

Takebe, Naoko, primary, Naqash, Abdul Rafeh, primary, O'Sullivan Coyne, Geraldine, primary, Kummar, Shivaani, primary, Do, Khanh, primary, Bruns, Ashley, primary, Juwara, Lamin, primary, Zlott, Jennifer, primary, Rubinstein, Larry, primary, Piekarz, Richard, primary, Sharon, Elad, primary, Streicher, Howard, primary, Mittra, Arjun, primary, Miller, Sarah B., primary, Ji, Jiuping, primary, Wilsker, Deborah, primary, Kinders, Robert J., primary, Parchment, Ralph E., primary, Chen, Li, primary, Chang, Ting-Chia, primary, Das, Biswajit, primary, Mugundu, Ganesh, primary, Doroshow, James H., primary, and Chen, Alice P., primary

Published
2023
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23. Supplementary Data from A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma

Author

Gounder, Mrinal M., primary, Rosenbaum, Evan, primary, Wu, Nian, primary, Dickson, Mark A., primary, Sheikh, Tahir N., primary, D'Angelo, Sandra P., primary, Chi, Ping, primary, Keohan, Mary Lou, primary, Erinjeri, Joseph P., primary, Antonescu, Cristina R., primary, Agaram, Narasimhan, primary, Hameed, Meera R., primary, Martindale, Moriah, primary, Lefkowitz, Robert A., primary, Crago, Aimee M., primary, Singer, Sam, primary, Tap, William D., primary, Takebe, Naoko, primary, Qin, Li-Xuan, primary, and Schwartz, Gary K., primary

Published
2023
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24. Supplementary Figures 1 - 2 from Phase I Study of Vismodegib in Children with Recurrent or Refractory Medulloblastoma: A Pediatric Brain Tumor Consortium Study

Author

Gajjar, Amar, primary, Stewart, Clinton F., primary, Ellison, David W., primary, Kaste, Sue, primary, Kun, Larry E., primary, Packer, Roger J., primary, Goldman, Stewart, primary, Chintagumpala, Murali, primary, Wallace, Dana, primary, Takebe, Naoko, primary, Boyett, James M., primary, Gilbertson, Richard J., primary, and Curran, Tom, primary

Published
2023
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25. Supplementary Data from Clinical Activity of Single-Agent Cabozantinib (XL184), a Multi-receptor Tyrosine Kinase Inhibitor, in Patients with Refractory Soft-Tissue Sarcomas

Author

O'Sullivan Coyne, Geraldine, primary, Kummar, Shivaani, primary, Hu, James, primary, Ganjoo, Kristen, primary, Chow, Warren A., primary, Do, Khanh T., primary, Zlott, Jennifer, primary, Bruns, Ashley, primary, Rubinstein, Lawrence, primary, Foster, Jared C., primary, Juwara, Lamin, primary, Meehan, Robert, primary, Piekarz, Richard, primary, Streicher, Howard, primary, Sharon, Elad, primary, Takebe, Naoko, primary, Voth, Andrea Regier, primary, Bottaro, Donald, primary, Costello, Rene, primary, Wright, John J., primary, Doroshow, James H., primary, and Chen, Alice P., primary

Published
2023
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26. Supplementary Data from Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors

Author

Takebe, Naoko, primary, Naqash, Abdul Rafeh, primary, O'Sullivan Coyne, Geraldine, primary, Kummar, Shivaani, primary, Do, Khanh, primary, Bruns, Ashley, primary, Juwara, Lamin, primary, Zlott, Jennifer, primary, Rubinstein, Larry, primary, Piekarz, Richard, primary, Sharon, Elad, primary, Streicher, Howard, primary, Mittra, Arjun, primary, Miller, Sarah B., primary, Ji, Jiuping, primary, Wilsker, Deborah, primary, Kinders, Robert J., primary, Parchment, Ralph E., primary, Chen, Li, primary, Chang, Ting-Chia, primary, Das, Biswajit, primary, Mugundu, Ganesh, primary, Doroshow, James H., primary, and Chen, Alice P., primary

Published
2023
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27. Supplemental Fig.1-4;Supplemental Tables 1-3; Suipplemental Methods from Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial

Author

Xu, Ran, primary, Shimizu, Fumiko, primary, Hovinga, Koos, primary, Beal, Kathryn, primary, Karimi, Sasan, primary, Droms, Leif, primary, Peck, Kyung K., primary, Gutin, Philip, primary, Iorgulescu, J. Bryan, primary, Kaley, Thomas, primary, DeAngelis, Lisa, primary, Pentsova, Elena, primary, Nolan, Craig, primary, Grommes, Christian, primary, Chan, Timothy, primary, Bobrow, Dylan, primary, Hormigo, Adilia, primary, Cross, Justin R., primary, Wu, Nian, primary, Takebe, Naoko, primary, Panageas, Katherine, primary, Ivy, Percy, primary, Supko, Jeffrey G., primary, Tabar, Viviane, primary, and Omuro, Antonio, primary

Published
2023
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29. Data from A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma

Author

Gounder, Mrinal M., primary, Rosenbaum, Evan, primary, Wu, Nian, primary, Dickson, Mark A., primary, Sheikh, Tahir N., primary, D'Angelo, Sandra P., primary, Chi, Ping, primary, Keohan, Mary Lou, primary, Erinjeri, Joseph P., primary, Antonescu, Cristina R., primary, Agaram, Narasimhan, primary, Hameed, Meera R., primary, Martindale, Moriah, primary, Lefkowitz, Robert A., primary, Crago, Aimee M., primary, Singer, Sam, primary, Tap, William D., primary, Takebe, Naoko, primary, Qin, Li-Xuan, primary, and Schwartz, Gary K., primary

Published
2023
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30. Supplementary Table 1 from Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Author

Kim, Edward J., primary, Sahai, Vaibhav, primary, Abel, Ethan V., primary, Griffith, Kent A., primary, Greenson, Joel K., primary, Takebe, Naoko, primary, Khan, Gazala N., primary, Blau, John L., primary, Craig, Ronald, primary, Balis, Ulysses G., primary, Zalupski, Mark M., primary, and Simeone, Diane M., primary

Published
2023
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32. Supplementary Figure 1 Legend from Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Author

Kim, Edward J., primary, Sahai, Vaibhav, primary, Abel, Ethan V., primary, Griffith, Kent A., primary, Greenson, Joel K., primary, Takebe, Naoko, primary, Khan, Gazala N., primary, Blau, John L., primary, Craig, Ronald, primary, Balis, Ulysses G., primary, Zalupski, Mark M., primary, and Simeone, Diane M., primary

Published
2023
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33. Supplementary Figure 1 from Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Author

Kim, Edward J., primary, Sahai, Vaibhav, primary, Abel, Ethan V., primary, Griffith, Kent A., primary, Greenson, Joel K., primary, Takebe, Naoko, primary, Khan, Gazala N., primary, Blau, John L., primary, Craig, Ronald, primary, Balis, Ulysses G., primary, Zalupski, Mark M., primary, and Simeone, Diane M., primary

Published
2023
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35. Supplementary Figures 1 - 2 from Phase I Study of Vismodegib in Children with Recurrent or Refractory Medulloblastoma: A Pediatric Brain Tumor Consortium Study

Author

Tom Curran, Richard J. Gilbertson, James M. Boyett, Naoko Takebe, Dana Wallace, Murali Chintagumpala, Stewart Goldman, Roger J. Packer, Larry E. Kun, Sue Kaste, David W. Ellison, Clinton F. Stewart, and Amar Gajjar

Abstract

PDF file - 156K, Supplementary Fig. S1. Concentration-time plots of the first 72 hours after administration of the first vismodegib dose during Course 1 to the patients in the initial cohort: 6 received 85 mg/m2 (Figure A & B), and 7 received 170 mg/m2 (Figure C &D). Plasma concentrations of total vismodegib (A, C) and unbound vismodegib (B, D) were measured. Supplementary Fig S2. The relation between total vismodegib plasma concentrations and alpha-1-acid glycoprotein (AAGP) plasma concentrations in pediatric patients. The scatter plot includes all data from patients treated in this study. The solid line represents the best-fit line from linear regression analysis (R2= 0.38).

Published
2023
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36. Supplemental Materials and Methods from Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use

Author

Ralph E. Parchment, James H. Doroshow, Shivaani Kummar, Joseph E. Tomaszewski, Naoko Takebe, Robert J. Kinders, James P. Mapes, Dominic Esposito, Jennifer Donohue, Jeevan Prasaad Govindharajulu, Eric Damour, Adam Layhee, Melinda G. Hollingshead, Laurie Stephen, Soumya Jaganathan, and Apurva K. Srivastava

Abstract

This file contains supplemental materials and methods describing protein calibrator preparation and pre-analytical variability

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2023
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37. Supplemental Fig.1-4;Supplemental Tables 1-3; Suipplemental Methods from Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial

Author

Antonio Omuro, Viviane Tabar, Jeffrey G. Supko, Percy Ivy, Katherine Panageas, Naoko Takebe, Nian Wu, Justin R. Cross, Adilia Hormigo, Dylan Bobrow, Timothy Chan, Christian Grommes, Craig Nolan, Elena Pentsova, Lisa DeAngelis, Thomas Kaley, J. Bryan Iorgulescu, Philip Gutin, Kyung K. Peck, Leif Droms, Sasan Karimi, Kathryn Beal, Koos Hovinga, Fumiko Shimizu, and Ran Xu

Abstract

Supp. Fig.1. CONSORT Flow Diagram Supp. Fig.2. MRI Perfusion Parameters Supp. Fig. 3. Immunohistochemistry Supp. Fig. 4. Gene Expression Profile Supp. Table 1. Adverse Events Supp. Table 2. Pharmacokinetic Data Supp. Table 3. Molar Drug Levels Supplemental Methods

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2023
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38. Data from Phase I Study of Vismodegib in Children with Recurrent or Refractory Medulloblastoma: A Pediatric Brain Tumor Consortium Study

Author

Tom Curran, Richard J. Gilbertson, James M. Boyett, Naoko Takebe, Dana Wallace, Murali Chintagumpala, Stewart Goldman, Roger J. Packer, Larry E. Kun, Sue Kaste, David W. Ellison, Clinton F. Stewart, and Amar Gajjar

Abstract

Purpose: To investigate the safety, dose-limiting toxicities, and pharmacokinetics of the smoothened inhibitor vismodegib in children with refractory or relapsed medulloblastoma.Experimental design: Initially, vismodegib was administered daily at 85 mg/m2 and escalated to 170 mg/m2. The study was then revised to investigate a flat-dosing schedule of 150 mg for patients with small body surface area (BSA, 0.67–1.32 m2) or 300 mg for those who were larger (BSA, 1.33–2.20 m2). Pharmacokinetics were performed during the first course of therapy, and the right knees of all patients were imaged to monitor bone toxicity. Immunohistochemical analysis was done to identify patients with Sonic Hedgehog (SHH)-subtype medulloblastoma.Results: Thirteen eligible patients were enrolled in the initial study: 6 received 85 mg/m2 vismodegib, and 7 received 170 mg/m2. Twenty eligible patients were enrolled in the flat-dosing part of the study: 10 at each dosage level. Three dose-limiting toxicities were observed, but no drug-related bone toxicity was documented. The median (range) vismodegib penetration in the cerebrospinal fluid (CSF) was 0.53 (0.26–0.78), when expressed as a ratio of the concentration of vismodegib in the CSF to that of the unbound drug in plasma. Antitumor activity was seen in 1 of 3 patients with SHH-subtype disease whose tumors were evaluable, and in none of the patients in the other subgroups.Conclusions: Vismodegib was well tolerated in children with recurrent or refractory medulloblastoma; only two dose-limiting toxicities were observed with flat dosing. The recommended phase II study dose is 150 or 300 mg, depending on the patient's BSA. Clin Cancer Res; 19(22); 6305–12. ©2013 AACR.

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2023
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39. Supplemental Figure S2 from Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use

Author

Ralph E. Parchment, James H. Doroshow, Shivaani Kummar, Joseph E. Tomaszewski, Naoko Takebe, Robert J. Kinders, James P. Mapes, Dominic Esposito, Jennifer Donohue, Jeevan Prasaad Govindharajulu, Eric Damour, Adam Layhee, Melinda G. Hollingshead, Laurie Stephen, Soumya Jaganathan, and Apurva K. Srivastava

Abstract

This file contains supplemental Figure S2: Temperature stability of analytes

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2023
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40. Supplementary Figure 1 Legend from Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Author

Diane M. Simeone, Mark M. Zalupski, Ulysses G. Balis, Ronald Craig, John L. Blau, Gazala N. Khan, Naoko Takebe, Joel K. Greenson, Kent A. Griffith, Ethan V. Abel, Vaibhav Sahai, and Edward J. Kim

Abstract

Supplementary Figure 1 Legend. Median overall survival correlated with change in CA 19-9 (>50% decrease, versus {less than or equal to}50% decrease, or primary increase)

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2023
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41. Supplementary Figure 1 from Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Author

Diane M. Simeone, Mark M. Zalupski, Ulysses G. Balis, Ronald Craig, John L. Blau, Gazala N. Khan, Naoko Takebe, Joel K. Greenson, Kent A. Griffith, Ethan V. Abel, Vaibhav Sahai, and Edward J. Kim

Abstract

Supplementary Figure 1. Median overall survival correlated with change in CA 19-9 (>50% decrease, versus {less than or equal to}50% decrease, or primary increase) compared to baseline.

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2023
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42. Data from A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma

Author

Gary K. Schwartz, Li-Xuan Qin, Naoko Takebe, William D. Tap, Sam Singer, Aimee M. Crago, Robert A. Lefkowitz, Moriah Martindale, Meera R. Hameed, Narasimhan Agaram, Cristina R. Antonescu, Joseph P. Erinjeri, Mary Lou Keohan, Ping Chi, Sandra P. D'Angelo, Tahir N. Sheikh, Mark A. Dickson, Nian Wu, Evan Rosenbaum, and Mrinal M. Gounder

Abstract

Purpose:Because the Hedgehog and Notch pathways are often overexpressed in mesenchymal malignancies, we evaluated the efficacy of concurrent inhibition of Notch and Hedgehog signaling using the gamma-secretase inhibitor (GSI) RO4929097 and the smoothened antagonist vismodegib in unresectable or metastatic sarcoma.Patients and Methods:In this investigator-initiated trial, phase Ib used standard 3+3 dose escalation in which patients first received vismodegib once daily for 21 days, followed by the combination of RO4929097 concurrently with vismodegib in 21-day cycles. In phase II, patients were randomized to RO4929097 alone or in combination with vismodegib.Results:Nine patients were treated in phase Ib with no dose-limiting toxicities. RO4929097 at 15 mg daily in combination with 150 mg daily of vismodegib was declared the recommended phase II dose. Most adverse events were grade ≤ 2. In phase II (closed early due to discontinuation of RO4929097 evaluation), 34 patients were randomized to RO4929097 alone and 33 to RO4929097 plus vismodegib. RO4929097 did not interfere with the steady-state concentration of vismodegib, while vismodegib reduced the plasma concentration of RO492909. No patients had an objective response. Neither progression-free nor overall survival differed significantly between treatment arms. Paired tumor biopsies from a subset of patients demonstrated inhibition of cleaved Notch.Conclusions:The combination of RO4929097 plus vismodegib was generally well tolerated. Although accrual to this study was not completed, vismodegib did not meaningfully enhance the clinical efficacy of RO4929097 in an unplanned analysis. GSIs and GSIs plus vismodegib can inhibit intratumoral Notch and downstream phosphorylated Akt signaling.

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2023
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43. Data from Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays Fit for Clinical Use

Author

Ralph E. Parchment, James H. Doroshow, Shivaani Kummar, Joseph E. Tomaszewski, Naoko Takebe, Robert J. Kinders, James P. Mapes, Dominic Esposito, Jennifer Donohue, Jeevan Prasaad Govindharajulu, Eric Damour, Adam Layhee, Melinda G. Hollingshead, Laurie Stephen, Soumya Jaganathan, and Apurva K. Srivastava

Abstract

Purpose: To support clinical pharmacodynamic evaluation of the Smac mimetic TL32711 (birinapant) and other apoptosis-targeting drugs, we describe the development, validation, and application of novel immunoassays for 15 cytosolic and membrane-associated proteins indicative of the induction, onset, and commitment to apoptosis in human tumors.Experimental Design: The multiplex immunoassays were constructed on the Luminex platform with apoptosis biomarkers grouped into three panels. Panel 1 contains Bak, Bax, total caspase-3, total lamin-B (intact and 45 kDa fragment), and Smac; panel 2 contains Bad, Bax–Bcl-2 heterodimer, Bcl-xL, Bim, and Mcl1; and panel 3 contains active (cleaved) caspase-3, Bcl-xL–Bak heterodimer, Mcl1–Bak heterodimer, pS99-Bad, and survivin. Antibody specificity was confirmed by immunoprecipitation and Western blot analysis.Results: Two laboratories analytically validated the multiplex immunoassays for application with core-needle biopsy samples processed to control preanalytical variables; the biologic variability for each biomarker was estimated from xenograft measurements. Studies of TL32711 in xenograft models confirmed a dose-dependent increase in activated caspase-3 6 hours after dosing and provided assay fit-for-purpose confirmation. Coincident changes in cytosolic lamin-B and subsequent changes in Bcl-xL provided correlative evidence of caspase-3 activation. The validated assay is suitable for use with clinical specimens; 14 of 15 biomarkers were quantifiable in patient core-needle biopsies.Conclusions: The validated multiplex immunoassays developed for this study provided proof of mechanism data for TL32711 and are suitable for quantifying apoptotic biomarkers in clinical trials. Clin Cancer Res; 22(4); 1000–10. ©2015 AACR.

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2023
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44. Supplementary Figures S1-S5 from SLFN11 Inactivation Induces Proteotoxic Stress and Sensitizes Cancer Cells to Ubiquitin Activating Enzyme Inhibitor TAK-243

Author

Yves Pommier, Naoko Takebe, Shinsaku Fukuda, Ken Cheng, Lu Chen, Sirisha Chakka, Shar-Yin N. Huang, Lisa M. Jenkins, Junko Murai, Ukhyun Jo, and Yasuhisa Murai

Abstract

FigureS1(A) Cell viability to TAK-243 in our drug screening. (B) SLFN11-KO cell lines in Li-7 by Western blotting. (C) CPT cytotoxicity in Li-7 SLFN11-WT and -KO cell lines. (D) The intensity of colony forming. (E) Cellular apoptosis by flow cytometry (F) Cleaved-PARP and cleaved-Caspase 3 by Western blotting. FigureS2(A, B) EdU incorporation in DU145 treated by TAK-243 for 24h or 48h. (C, D) Fork elongation speed. The length of red or green-colored part. FigureS3 (A) DNA damage response (DDR) proteins after long-term TAK-243 treatment. (B) CHK1 activation by CPT is reduced by the ATR inhibitor. FigureS4(A) UPR Activation by TAK-243 in CCRF-CEM cells. (B, C) UPR Activation by long-term TAK-243 treatment in DU145 and DMS114. (D) Accumulation of short-lived proteins. (E-F) Cell viability with p97 inhibitors in DU145. (G-H) Ubiquitin conjugates in CCRF-CEM with TAK-243 (1 hour). (I-J) Ubiquitin conjugates changes in DU145 cells with TAK-243(24 hours). FigureS5 (A-C) Newly synthesized protein detection by L-HPG in Li-7. Representative image and quantitation (D) Gene ontology (GO) analysis of molecular network associated with SLFN11. (E-F) Validation of SLFN11 interactions with the indicated translation initiation (EIF3B and EIF3L) and protein folding (CCT2) factors. (G) Relative cell viability with gene depletion of the TRiC/CCT chaperonin complex in RNAi screening. (H) Cell viability after transfection with siCCT2.

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2023
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45. Data from Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial

Author

Antonio Omuro, Viviane Tabar, Jeffrey G. Supko, Percy Ivy, Katherine Panageas, Naoko Takebe, Nian Wu, Justin R. Cross, Adilia Hormigo, Dylan Bobrow, Timothy Chan, Christian Grommes, Craig Nolan, Elena Pentsova, Lisa DeAngelis, Thomas Kaley, J. Bryan Iorgulescu, Philip Gutin, Kyung K. Peck, Leif Droms, Sasan Karimi, Kathryn Beal, Koos Hovinga, Fumiko Shimizu, and Ran Xu

Abstract

Purpose: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role.Experimental Design: In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood–brain barrier disruption. Finally, recurrent tumors were also sampled and assessed for Notch pathway responses while on treatment.Results: Treatment was well tolerated and no dose-limiting toxicities were observed. IHC of treated tumors showed a significant decrease in proliferation and in the expression of the Notch intracellular domain (NICD) by tumor cells and blood vessels. Patient-specific organotypic tumor explants cultures revealed a specific decrease in the CD133+ CIS population upon treatment. Perfusion MRI demonstrated a significant decrease in relative plasma volume after drug exposure. Gene expression data in recurrent tumors suggested low Notch signaling activity, the upregulation of key mesenchymal genes, and an increase in VEGF-dependent angiogenic factors.Conclusions: The addition of RO4929097 to temozolomide and radiotherapy was well tolerated; the drug has a variable blood–brain barrier penetration. Evidence of target modulation was observed, but recurrence occurred, associated with alterations in angiogenesis signaling pathways. Clin Cancer Res; 22(19); 4786–96. ©2016 AACR.

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2023
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46. Data from Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Author

Diane M. Simeone, Mark M. Zalupski, Ulysses G. Balis, Ronald Craig, John L. Blau, Gazala N. Khan, Naoko Takebe, Joel K. Greenson, Kent A. Griffith, Ethan V. Abel, Vaibhav Sahai, and Edward J. Kim

Abstract

Purpose: The hedgehog (HH) signaling pathway is a key regulator in tumorigenesis of pancreatic adenocarcinoma and is upregulated in pancreatic adenocarcinoma cancer stem cells (CSCs). GDC-0449 is an oral small-molecule inhibitor of the HH pathway. This study assessed the effect of GDC-0449–mediated HH inhibition in paired biopsies, followed by combined treatment with gemcitabine, in patients with metastatic pancreatic adenocarcinoma.Experimental Design: Twenty-five patients were enrolled of which 23 underwent core biopsies at baseline and following 3 weeks of GDC-0449. On day 29, 23 patients started weekly gemcitabine while continuing GDC-0449. We evaluated GLI1 and PTCH1 inhibition, change in CSCs, Ki-67, fibrosis, and assessed tumor response, survival and toxicity.Results: On pretreatment biopsy, 75% of patients had elevated sonic hedgehog (SHH) expression. On posttreatment biopsy, GLI1 and PTCH1 decreased in 95.6% and 82.6% of 23 patients, fibrosis decreased in 45.4% of 22, and Ki-67 in 52.9% of 17 evaluable patients. No significant changes were detected in CSCs pre- and postbiopsy. The median progression-free and overall survival for all treated patients were 2.8 and 5.3 months. The response and disease control rate was 21.7% and 65.2%. No significant correlation was noted between CSCs, fibrosis, SHH, Ki-67, GLI1, PTCH1 (baseline values or relative change on posttreatment biopsy), and survival. Grade ≥3 adverse events were noted in 56% of patients.Conclusion: We show that GDC-0449 for 3 weeks leads to downmodulation of GLI1 and PTCH1, without significant changes in CSCs compared with baseline. GDC-0449 and gemcitabine were not superior to gemcitabine alone in the treatment of metastatic pancreatic cancer. Clin Cancer Res; 20(23); 5937–45. ©2014 AACR.

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2023
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47. Data from Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors

Author

Alice P. Chen, James H. Doroshow, Ganesh Mugundu, Biswajit Das, Ting-Chia Chang, Li Chen, Ralph E. Parchment, Robert J. Kinders, Deborah Wilsker, Jiuping Ji, Sarah B. Miller, Arjun Mittra, Howard Streicher, Elad Sharon, Richard Piekarz, Larry Rubinstein, Jennifer Zlott, Lamin Juwara, Ashley Bruns, Khanh Do, Shivaani Kummar, Geraldine O'Sullivan Coyne, Abdul Rafeh Naqash, and Naoko Takebe

Abstract

Purpose:The Wee1 kinase inhibitor adavosertib abrogates cell-cycle arrest, leading to cell death. Prior testing of twice-daily adavosertib in patients with advanced solid tumors determined the recommended phase II dose (RPh2D). Here, we report results for once-daily adavosertib.Patients and Methods:A 3 + 3 dose-escalation design was used, with adavosertib given once daily on days 1 to 5 and 8 to 12 in 21-day cycles. Molecular biomarkers of Wee1 activity, including tyrosine 15–phosphorylated Cdk1/2 (pY15-Cdk), were assessed in paired tumor biopsies. Whole-exome sequencing and RNA sequencing of remaining tumor tissue identified potential predictive biomarkers.Results:Among the 42 patients enrolled, the most common toxicities were gastrointestinal and hematologic; dose-limiting toxicities were grade 4 hematologic toxicity and grade 3 fatigue. The once-daily RPh2D was 300 mg. Six patients (14%) had confirmed partial responses: four ovarian, two endometrial. Adavosertib plasma exposures were similar to those from twice-daily dosing. On cycle 1 day 8 (pre-dose), tumor pY15-Cdk levels were higher than baseline in four of eight patients, suggesting target rebound during the day 5 to 8 dosing break. One patient who progressed rapidly had a tumor WEE1 mutation and potentially compensatory PKMYT1 overexpression. Baseline CCNE1 overexpression occurred in both of two responding patients, only one of whom had CCNE1 amplification, and in zero of three nonresponding patients.Conclusions:We determined the once-daily adavosertib RPh2D and observed activity in patients with ovarian or endometrial carcinoma, including two with baseline CCNE1 mRNA overexpression. Future studies will determine whether CCNE1 overexpression is a predictive biomarker for adavosertib.

Published
2023
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48. Supplemental Figure 1 from Combined KIT and CTLA-4 Blockade in Patients with Refractory GIST and Other Advanced Sarcomas: A Phase Ib Study of Dasatinib plus Ipilimumab

Author

William D. Tap, Richard D. Carvajal, Ronald P. DeMatteo, Cristina Antonescu, Li-Xuan Qin, Naoko Takebe, Howard Streicher, Ana Sjoberg, Mark J. Bluth, Joseph Patrick Erinjeri, Zarine Patel, Lee Schneider, Leigh Gaffney, Jennifer K. Loo, Ping Chi, Mrinal M. Gounder, Mark A. Dickson, Mary Louise Keohan, Alexander N. Shoushtari, and Sandra P. D'Angelo

Abstract

Synergy of dasatinib and anti-CTLA-4. Using murine GIST mouse, it was observed that treatment with the KIT-targeted dasatinib for 7 days alone or with chronic anti-CTLA-4 alone decreased tumor volume initially; however tumors rapidly re-grew. Mice treated with KIT-targeted TKI for 7 days and chronic anti-CTLA-4 blockade showed augmentation and durability of the initial response. KITV5880+ mice received dasatinib 15mg/kg i.p. bid (Bristol Myers Squibb) on days 1 through 7, with or without anti-CTLA-5 (BioXcell.) Mice were imaged at baseline and serially during therapy using MRI and volumetric analysis was done using Image K software. Anti-CTLA-4 dosing regimen 200 microgram of clone 9H10 i.p. on day 3, then 100 microgram on day 6, 9 and 12, followed by clone 9D (100 micrograms i.p. every 3 days thereafter.)

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2023
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49. Supplementary Data from Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors

Author

Alice P. Chen, James H. Doroshow, Ganesh Mugundu, Biswajit Das, Ting-Chia Chang, Li Chen, Ralph E. Parchment, Robert J. Kinders, Deborah Wilsker, Jiuping Ji, Sarah B. Miller, Arjun Mittra, Howard Streicher, Elad Sharon, Richard Piekarz, Larry Rubinstein, Jennifer Zlott, Lamin Juwara, Ashley Bruns, Khanh Do, Shivaani Kummar, Geraldine O'Sullivan Coyne, Abdul Rafeh Naqash, and Naoko Takebe

Abstract

Supplementary Methods, Supplementary Fig. S1 (Mean adavosertib plasma concentrations for QD vs. BID schedules), Supplementary Fig. S2 (Example PD biomarker immunofluorescence images), Supplementary Fig. S3 (CCNE1 tumor alteration frequency IMPACT data), Supplementary Fig. S4 (Independence of tumor CCNE1 mRNA expression and CCNE1 CNA in TCGA ovarian and endometrial cohorts), Supplementary Table S1 (DLTs), Supplementary Table S2 (Non-DLT dose reductions), Supplementary Table S3 (Responses and baseline genomic characteristics for patients with ovarian carcinoma and prior PARP inhibitor therapy), Supplementary Table S4 (Mean Cycle 1 Day 1 PK parameters), Supplementary Table S5 (Patient tumor mutations identified by WES), Supplementary References

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2023
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50. Supplementary Data from A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma

Author

Gary K. Schwartz, Li-Xuan Qin, Naoko Takebe, William D. Tap, Sam Singer, Aimee M. Crago, Robert A. Lefkowitz, Moriah Martindale, Meera R. Hameed, Narasimhan Agaram, Cristina R. Antonescu, Joseph P. Erinjeri, Mary Lou Keohan, Ping Chi, Sandra P. D'Angelo, Tahir N. Sheikh, Mark A. Dickson, Nian Wu, Evan Rosenbaum, and Mrinal M. Gounder

Abstract

Supplementary Data from A Phase Ib/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma

Published
2023
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