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145 results on '"Gusenleitner, Daniel"'

1. Improving Specificity for Ovarian Cancer Screening Using a Novel Extracellular Vesicle–Based Blood Test: Performance in a Training and Verification Cohort

Author

Winn-Deen, Emily S., Bortolin, Laura T., Gusenleitner, Daniel, Biette, Kelly M., Copeland, Karen, Gentry-Maharaj, Aleksandra, Apostolidou, Sophia, Couvillon, Anthony D., Salem, Daniel P., Banerjee, Sanchari, Grosha, Jonian, Zabroski, Ibukunoluwapo O., Sedlak, Christopher R., Byrne, Delaney M., Hamzeh, Bilal F., King, MacKenzie S., Cuoco, Lauren T., Duff, Peter A., Manning, Brendan J., Hawkins, Troy B., Mattoon, Dawn, Guettouche, Toumy, Skates, Steven J., Jamieson, Amy, McAlpine, Jessica N., Huntsman, David, and Menon, Usha

Published
2024
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2. Spartalizumab or placebo in combination with dabrafenib and trametinib in patients with BRAF V600-mutant melanoma: exploratory biomarker analyses from a randomized phase 3 trial (COMBI-i)

Author

Tawbi, Hussein A, Robert, Caroline, Brase, Jan C, Gusenleitner, Daniel, Gasal, Eduard, Garrett, James, Savchenko, Alexander, Görgün, Güllü, Flaherty, Keith T, Ribas, Antoni, Dummer, Reinhard, Schadendorf, Dirk, Long, Georgina V, Nathan, Paul D, and Ascierto, Paolo A

Subjects
Genetics, Cancer, Clinical Trials and Supportive Activities, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, B7-H1 Antigen, Biomarkers, Tumor, Clinical Trials, Phase III as Topic, Humans, Imidazoles, Melanoma, Oximes, Proto-Oncogene Proteins B-raf, Pyridones, Pyrimidinones, Randomized Controlled Trials as Topic, Skin Neoplasms, Drug Therapy, Combination, Tumor Biomarkers
Abstract

BackgroundThe randomized phase 3 COMBI-i trial did not meet its primary endpoint of improved progression-free survival (PFS) with spartalizumab plus dabrafenib and trametinib (sparta-DabTram) vs placebo plus dabrafenib and trametinib (placebo-DabTram) in the overall population of patients with unresectable/metastatic BRAF V600-mutant melanoma. This prespecified exploratory biomarker analysis was performed to identify subgroups that may derive greater treatment benefit from sparta-DabTram.MethodsIn COMBI-i (ClinicalTrials.gov, NCT02967692), 532 patients received spartalizumab 400 mg intravenously every 4 weeks plus dabrafenib 150 mg orally two times daily and trametinib 2 mg orally one time daily or placebo-DabTram. Baseline/on-treatment pharmacodynamic markers were assessed via flow cytometry-based immunophenotyping and plasma cytokine profiling. Baseline programmed death ligand 1 (PD-L1) status and T-cell phenotype were assessed via immunohistochemistry; BRAF V600 mutation type, tumor mutational burden (TMB), and circulating tumor DNA (ctDNA) via DNA sequencing; gene expression signatures via RNA sequencing; and CD4+/CD8+ T-cell ratio via immunophenotyping.ResultsExtensive biomarker analyses were possible in approximately 64% to 90% of the intention-to-treat population, depending on sample availability and assay. Subgroups based on PD-L1 status/TMB or T-cell inflammation did not show significant differences in PFS benefit with sparta-DabTram vs placebo-DabTram, although T-cell inflammation was prognostic across treatment arms. Subgroups defined by BRAF V600K mutation (HR 0.45 (95% CI 0.21 to 0.99)), detectable ctDNA shedding (HR 0.75 (95% CI 0.58 to 0.96)), or CD4+/CD8+ ratio above median (HR 0.58 (95% CI 0.40 to 0.84)) derived greater PFS benefit with sparta-DabTram vs placebo-DabTram. In a multivariate analysis, ctDNA emerged as strongly prognostic (p=0.007), while its predictive trend did not reach significance; in contrast, CD4+/CD8+ ratio was strongly predictive (interaction p=0.0131).ConclusionsThese results support the feasibility of large-scale comprehensive biomarker analyses in the context of a global phase 3 study. T-cell inflammation was prognostic but not predictive of sparta-DabTram benefit, as patients with high T-cell inflammation already benefit from targeted therapy alone. Baseline ctDNA shedding also emerged as a strong independent prognostic variable, with predictive trends consistent with established measures of disease burden such as lactate dehydrogenase levels. CD4+/CD8+ T-cell ratio was significantly predictive of PFS benefit with sparta-DabTram but requires further validation as a biomarker in melanoma. Taken together with previous observations, further study of checkpoint inhibitor plus targeted therapy combination in patients with higher disease burden may be warranted.Trial registration numberNCT02967692.

Published
2022

3. Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma

Author

Váraljai, Renáta, Zimmer, Lisa, Al-Matary, Yahya, Kaptein, Paulien, Albrecht, Lea J., Shannan, Batool, Brase, Jan C., Gusenleitner, Daniel, Amaral, Teresa, Wyss, Nina, Utikal, Jochen, Flatz, Lukas, Rambow, Florian, Reinhardt, Hans Christian, Dick, Jenny, Engel, Daniel R., Horn, Susanne, Ugurel, Selma, Sondermann, Wiebke, Livingstone, Elisabeth, Sucker, Antje, Paschen, Annette, Zhao, Fang, Placke, Jan M., Klose, Jasmin M., Fendler, Wolfgang P., Thommen, Daniela S., Helfrich, Iris, Schadendorf, Dirk, and Roesch, Alexander

Published
2023
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4. Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus TrametinibTumor B-Cell Role in Outcome With Dabrafenib + Trametinib

Author

Brase, Jan C, Walter, Robert FH, Savchenko, Alexander, Gusenleitner, Daniel, Garrett, James, Schimming, Tobias, Varaljai, Renata, Castelletti, Deborah, Kim, Ju, Dakappagari, Naveen, Schultz, Ken, Robert, Caroline, Long, Georgina V, Nathan, Paul D, Ribas, Antoni, Flaherty, Keith T, Karaszewska, Boguslawa, Schachter, Jacob, Sucker, Antje, Schmid, Kurt W, Zimmer, Lisa, Livingstone, Elisabeth, Gasal, Eduard, Schadendorf, Dirk, and Roesch, Alexander

Subjects
Cancer, Clinical Trials and Supportive Activities, Genetics, Clinical Research, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Antineoplastic Combined Chemotherapy Protocols, B-Lymphocytes, Humans, Imidazoles, Melanoma, Oximes, Pyridones, Pyrimidinones, Skin Neoplasms, Treatment Outcome, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeAlthough patients with unresectable or metastatic melanoma can experience long-term survival with BRAF- and MEK-targeted agents or immune checkpoint inhibitors over 5 years, resistance develops in most patients. There is a distinct lack of pretherapeutic biomarkers to identify which patients are likely to benefit from each therapy type. Most research has focused on the predictive role of T cells in antitumor responses as opposed to B cells.Patients and methodsWe conducted prespecified exploratory biomarker analysis using gene expression profiling and digital pathology in 146 patients with previously untreated BRAF V600-mutant metastatic melanoma from the randomized, phase III COMBI-v trial and treated with dabrafenib plus trametinib who had available tumor specimens from screening.ResultsBaseline cell-cycle gene expression signature was associated with progression-free survival (P = 0.007). Patients with high T-cell/low B-cell gene signatures had improved median overall survival (not reached [95% confidence interval (CI), 33.8 months-not reached]) compared with patients with high T-cell/high B-cell signatures (19.1 months; 95% CI, 13.4-38.6 months). Patients with high B-cell signatures had high B-cell infiltration into the tumor compartment, corresponding with decreased MAPK activity and increased expression of immunosuppressive markers.ConclusionsB cells may serve as a potential biomarker to predict clinical outcome in patients with advanced melanoma treated with dabrafenib plus trametinib. As separate studies have shown an opposite effect for B-cell levels and response to immunotherapy, B cells may serve as a potential biomarker to facilitate treatment selection. Further validation in a larger patient cohort is needed.

Published
2021

5. Author Correction: Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma

Author

Váraljai, Renáta, Zimmer, Lisa, Al-Matary, Yahya, Kaptein, Paulien, Albrecht, Lea J., Shannan, Batool, Brase, Jan C., Gusenleitner, Daniel, Amaral, Teresa, Wyss, Nina, Utikal, Jochen, Flatz, Lukas, Rambow, Florian, Reinhardt, Hans Christian, Dick, Jenny, Engel, Daniel R., Horn, Susanne, Ugurel, Selma, Sondermann, Wiebke, Livingstone, Elisabeth, Sucker, Antje, Paschen, Annette, Zhao, Fang, Placke, Jan M., Klose, Jasmin M., Fendler, Wolfgang P., Thommen, Daniela S., Helfrich, Iris, Schadendorf, Dirk, and Roesch, Alexander

Published
2023
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6. Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma

Author

Griffin, Gabriel K., Weirather, Jason L., Roemer, Margaretha G.M., Lipschitz, Mikel, Kelley, Alyssa, Chen, Pei-Hsuan, Gusenleitner, Daniel, Jeter, Erin, Pak, Christine, Gjini, Evisa, Chapuy, Bjoern, Rosenthal, Michael H., Xu, Jie, Chen, Benjamin J., Sohani, Aliyah R., Lovitch, Scott B., Abramson, Jeremy S., Ishizuka, Jeffrey J., Kim, Austin I., Jacobson, Caron A., LaCasce, Ann S., Fletcher, Christopher D., Neuberg, Donna, Freeman, Gordon J., Hodi, F. Stephen, Wright, Kyle, Ligon, Azra H., Jacobsen, Eric D., Armand, Philippe, Shipp, Margaret A., and Rodig, Scott J.

Published
2021
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7. Adjuvant dabrafenib plus trametinib versus placebo in patients with resected, BRAFV600-mutant, stage III melanoma (COMBI-AD): exploratory biomarker analyses from a randomised, phase 3 trial

Author

Dummer, Reinhard, Brase, Jan C, Garrett, James, Campbell, Catarina D, Gasal, Eduard, Squires, Matthew, Gusenleitner, Daniel, Santinami, Mario, Atkinson, Victoria, Mandalà, Mario, Chiarion-Sileni, Vanna, Flaherty, Keith, Larkin, James, Robert, Caroline, Kefford, Richard, Kirkwood, John M, Hauschild, Axel, Schadendorf, Dirk, and Long, Georgina V

Published
2020
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8. Abstract A040: Improving specificity for ovarian cancer screening using a novel extracellular vesicle-based blood test

Author

Winn-Deen, Emily S., primary, Banerjee, Sanchari, additional, Gusenleitner, Daniel, additional, Bortolin, Laura T., additional, Grosha, Jonian, additional, Biette, Kelly M., additional, Copeland, Karen, additional, Sedlak, Christopher R., additional, Hamzeh, Bilal, additional, Couvillon, Anthony D., additional, Byrne, Delaney M., additional, Duff, Peter A., additional, Cuoco, Lauren T., additional, King, MacKenzie S., additional, Gentry-Maharaj, Aleksandra, additional, Apostolidou, Sophia, additional, Mattoon, Dawn R., additional, Berg, Christine D., additional, Ransohoff, David F., additional, Skates, Steven J., additional, and Menon, Usha, additional

Published
2024
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9. Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i

Author

Dummer, Reinhard, Lebbé, Celeste, Atkinson, Victoria, Mandalà, Mario, Nathan, Paul D., Arance, Ana, Richtig, Erika, Yamazaki, Naoya, Robert, Caroline, Schadendorf, Dirk, Tawbi, Hussein A., Ascierto, Paolo A., Ribas, Antoni, Flaherty, Keith T., Pakhle, Neha, Campbell, Catarina D., Gusenleitner, Daniel, Masood, Aisha, Brase, Jan C., Gasal, Eduard, and Long, Georgina V.

Published
2020
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10. A phase 2, multicenter, open-label study of anti-LAG-3 ieramilimab in combination with anti-PD-1 spartalizumab in patients with advanced solid malignancies

Author

Lin, Chia-Chi, primary, Garralda, Elena, additional, Schöffski, Patrick, additional, Hong, David S., additional, Siu, Lillian L., additional, Martin, Miguel, additional, Maur, Michela, additional, Hui, Rina, additional, Soo, Ross A, additional, Chiu, Joanne, additional, Zhang, Tian, additional, Ma, Brigette, additional, Kyi, Chrisann, additional, Tan, Daniel SW, additional, Cassier, Philippe A., additional, Sarantopoulos, John, additional, Weickhardt, Andrew, additional, Carvajal, Richard D., additional, Spratlin, Jennifer, additional, Esaki, Taito, additional, Rolland, Fréderic, additional, Akerley, Wallace, additional, Deschler-Baier, Barbara, additional, Rispoli, Lawrence, additional, Samant, Tanay S., additional, Chowdhury, Niladri Roy, additional, Gusenleitner, Daniel, additional, Kwak, Eunice L., additional, Askoxylakis, Vasileios, additional, and De Braud, Filippo, additional

Published
2023
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11. Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade

Author

Shukla, Sachet A., Bachireddy, Pavan, Schilling, Bastian, Galonska, Christina, Zhan, Qian, Bango, Clyde, Langer, Rupert, Lee, Patrick C., Gusenleitner, Daniel, Keskin, Derin B., Babadi, Mehrtash, Mohammad, Arman, Gnirke, Andreas, Clement, Kendell, Cartun, Zachary J., Van Allen, Eliezer M., Miao, Diana, Huang, Ying, Snyder, Alexandra, Merghoub, Taha, Wolchok, Jedd D., Garraway, Levi A., Meissner, Alexander, Weber, Jeffrey S., Hacohen, Nir, Neuberg, Donna, Potts, Patrick R., Murphy, George F., Lian, Christine G., Schadendorf, Dirk, Hodi, F. Stephen, and Wu, Catherine J.

Published
2018
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14. Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biological heterogeneity of the disease

Author

Chapuy, Bjoern, Cheng, Hongwei, Watahiki, Akira, Ducar, Matthew D., Tan, Yuxiang, Chen, Linfeng, Roemer, Margaretha G.M., Ouyang, Jing, Christie, Amanda L., Zhang, Liye, Gusenleitner, Daniel, Abo, Ryan P., Farinha, Pedro, von Bonin, Frederike, Thorner, Aaron R., Sun, Heather H., Gascoyne, Randy D., Pinkus, Geraldine S., van Hummelen, Paul, Wulf, Gerald G., Aster, Jon C., Weinstock, David M., Monti, Stefano, Rodig, Scott J., Wang, Yuzhuo, and Shipp, Margaret A.

Published
2016
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15. Targetable genetic features of primary testicular and primary central nervous system lymphomas

Author

Chapuy, Bjoern, Roemer, Margaretha G.M., Stewart, Chip, Tan, Yuxiang, Abo, Ryan P., Zhang, Liye, Dunford, Andrew J., Meredith, David M., Thorner, Aaron R., Jordanova, Ekaterina S., Liu, Gang, Feuerhake, Friedrich, Ducar, Matthew D., Illerhaus, Gerald, Gusenleitner, Daniel, Linden, Erica A., Sun, Heather H., Homer, Heather, Aono, Miyuki, Pinkus, Geraldine S., Ligon, Azra H., Ligon, Keith L., Ferry, Judith A., Freeman, Gordon J., van Hummelen, Paul, Golub, Todd R., Getz, Gad, Rodig, Scott J., de Jong, Daphne, Monti, Stefano, and Shipp, Margaret A.

Published
2016
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16. Supplementary Tables from Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib

Author

Brase, Jan C., primary, Walter, Robert F.H., primary, Savchenko, Alexander, primary, Gusenleitner, Daniel, primary, Garrett, James, primary, Schimming, Tobias, primary, Varaljai, Renata, primary, Castelletti, Deborah, primary, Kim, Ju, primary, Dakappagari, Naveen, primary, Schultz, Ken, primary, Robert, Caroline, primary, Long, Georgina V., primary, Nathan, Paul D., primary, Ribas, Antoni, primary, Flaherty, Keith T., primary, Karaszewska, Boguslawa, primary, Schachter, Jacob, primary, Sucker, Antje, primary, Schmid, Kurt W., primary, Zimmer, Lisa, primary, Livingstone, Elisabeth, primary, Gasal, Eduard, primary, Schadendorf, Dirk, primary, and Roesch, Alexander, primary

Published
2023
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17. Supplementary Data from Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib

Author

Brase, Jan C., primary, Walter, Robert F.H., primary, Savchenko, Alexander, primary, Gusenleitner, Daniel, primary, Garrett, James, primary, Schimming, Tobias, primary, Varaljai, Renata, primary, Castelletti, Deborah, primary, Kim, Ju, primary, Dakappagari, Naveen, primary, Schultz, Ken, primary, Robert, Caroline, primary, Long, Georgina V., primary, Nathan, Paul D., primary, Ribas, Antoni, primary, Flaherty, Keith T., primary, Karaszewska, Boguslawa, primary, Schachter, Jacob, primary, Sucker, Antje, primary, Schmid, Kurt W., primary, Zimmer, Lisa, primary, Livingstone, Elisabeth, primary, Gasal, Eduard, primary, Schadendorf, Dirk, primary, and Roesch, Alexander, primary

Published
2023
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18. Supplementary Figures from Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib

Author

Brase, Jan C., primary, Walter, Robert F.H., primary, Savchenko, Alexander, primary, Gusenleitner, Daniel, primary, Garrett, James, primary, Schimming, Tobias, primary, Varaljai, Renata, primary, Castelletti, Deborah, primary, Kim, Ju, primary, Dakappagari, Naveen, primary, Schultz, Ken, primary, Robert, Caroline, primary, Long, Georgina V., primary, Nathan, Paul D., primary, Ribas, Antoni, primary, Flaherty, Keith T., primary, Karaszewska, Boguslawa, primary, Schachter, Jacob, primary, Sucker, Antje, primary, Schmid, Kurt W., primary, Zimmer, Lisa, primary, Livingstone, Elisabeth, primary, Gasal, Eduard, primary, Schadendorf, Dirk, primary, and Roesch, Alexander, primary

Published
2023
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21. Spartalizumab or placebo in combination with dabrafenib and trametinib in patients with $\textit{BRAF}$V600-mutant melanoma: exploratory biomarker analyses from a randomized phase 3 trial (COMBI-i)

Author

Tawbi, Hussein A; https://orcid.org/0000-0003-1942-851X, Robert, Caroline; https://orcid.org/0000-0002-9493-0238, Brase, Jan C; https://orcid.org/0000-0002-1325-2528, Gusenleitner, Daniel, Gasal, Eduard, Garrett, James, Savchenko, Alexander, Görgün, Güllü, Flaherty, Keith T; https://orcid.org/0000-0002-3402-0478, Ribas, Antoni; https://orcid.org/0000-0003-3669-8458, Dummer, Reinhard; https://orcid.org/0000-0002-2279-6906, Schadendorf, Dirk; https://orcid.org/0000-0003-3524-7858, Long, Georgina V; https://orcid.org/0000-0001-8894-3545, Nathan, Paul D; https://orcid.org/0000-0002-2327-3250, Ascierto, Paolo A; https://orcid.org/0000-0002-8322-475X, Tawbi, Hussein A; https://orcid.org/0000-0003-1942-851X, Robert, Caroline; https://orcid.org/0000-0002-9493-0238, Brase, Jan C; https://orcid.org/0000-0002-1325-2528, Gusenleitner, Daniel, Gasal, Eduard, Garrett, James, Savchenko, Alexander, Görgün, Güllü, Flaherty, Keith T; https://orcid.org/0000-0002-3402-0478, Ribas, Antoni; https://orcid.org/0000-0003-3669-8458, Dummer, Reinhard; https://orcid.org/0000-0002-2279-6906, Schadendorf, Dirk; https://orcid.org/0000-0003-3524-7858, Long, Georgina V; https://orcid.org/0000-0001-8894-3545, Nathan, Paul D; https://orcid.org/0000-0002-2327-3250, and Ascierto, Paolo A; https://orcid.org/0000-0002-8322-475X

Abstract

BackgroundThe randomized phase 3 COMBI-i trial did not meet its primary endpoint of improved progression-free survival (PFS) with spartalizumab plus dabrafenib and trametinib (sparta-DabTram) vs placebo plus dabrafenib and trametinib (placebo-DabTram) in the overall population of patients with unresectable/metastatic $\textit{BRAF}$V600-mutant melanoma. This prespecified exploratory biomarker analysis was performed to identify subgroups that may derive greater treatment benefit from sparta-DabTram.MethodsIn COMBI-i (ClinicalTrials.gov, NCT02967692), 532 patients received spartalizumab 400 mg intravenously every 4 weeks plus dabrafenib 150 mg orally two times daily and trametinib 2 mg orally one time daily or placebo-DabTram. Baseline/on-treatment pharmacodynamic markers were assessed via flow cytometry-based immunophenotyping and plasma cytokine profiling. Baseline programmed death ligand 1 (PD-L1) status and T-cell phenotype were assessed via immunohistochemistry; $\textit{BRAF}$V600 mutation type, tumor mutational burden (TMB), and circulating tumor DNA (ctDNA) via DNA sequencing; gene expression signatures via RNA sequencing; and CD4$^{+}$/CD8$^{+}$ T-cell ratio via immunophenotyping.ResultsExtensive biomarker analyses were possible in approximately 64% to 90% of the intention-to-treat population, depending on sample availability and assay. Subgroups based on PD-L1 status/TMB or T-cell inflammation did not show significant differences in PFS benefit with sparta-DabTram vs placebo-DabTram, although T-cell inflammation was prognostic across treatment arms. Subgroups defined by $\textit{BRAF}$V600K mutation (HR 0.45 (95% CI 0.21 to 0.99)), detectable ctDNA shedding (HR 0.75 (95% CI 0.58 to 0.96)), or CD4$^{+}$/CD8$^{+}$ ratio above median (HR 0.58 (95% CI 0.40 to 0.84)) derived greater PFS benefit with sparta-DabTram vs placebo-DabTram. In a multivariate analysis, ctDNA emerged as strongly prognostic (p=0.007), while its predictive trend did not reach significance

Published
2022

22. Abstract 2232: Preliminary results for a novel single extracellular vesicle assay for early lung cancer: The power of co-localized detection of surface biomarkers

Author

Salem, Daniel P., primary, Bortolin, Laura T., additional, Banerjee, Sanchari, additional, Biette, Kelly M., additional, Byrne, Delaney M., additional, Couvillon, Anthony D., additional, Duff, Peter A., additional, Grosha, Jonian, additional, Gusenleitner, Daniel, additional, King, MacKenzie Sadie, additional, Sedlak, Christopher R., additional, Zabroski, Ibukunoluwapo O., additional, Copeland, Karen, additional, Winn-Deen, Emily S., additional, Huang, Eric K., additional, Berg, Christine D., additional, and Sedlak, Joseph C., additional

Published
2022
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23. Abstract 3390: Preliminary results for a novel single extracellular vesicle assay for early stage ovarian cancer: The power of co-localized detection of surface biomarkers

Author

Bortolin, Laura T., primary, Salem, Daniel P., additional, Banerjee, Sanchari, additional, Biette, Kelly M., additional, Byrne, Delaney M., additional, Couvillon, Anthony D., additional, Duff, Peter A., additional, Grosha, Jonian, additional, King, MacKenzie Sadie, additional, Sedlak, Christopher R., additional, Zabroski, Ibukunoluwapo O., additional, Alexander, Claire, additional, Copeland, Karen, additional, Gusenleitner, Daniel, additional, Winn-Deen, Emily S., additional, Huang, Eric K., additional, Rueda, Bo R., additional, and Sedlak, Joseph Charles, additional

Published
2022
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24. Extracellular vesicle-based biomarker assay for the detection of early-stage ovarian cancer.

Author

Bortolin, Laura, primary, Salem, Daniel P., additional, Grosha, Jonian, additional, Zabroski, Ibukunoluwapo O., additional, Banerjee, Sanchari, additional, Gusenleitner, Daniel, additional, Biette, Kelly M., additional, Sedlak, Christopher R., additional, Couvillon, Anthony D., additional, Duff, Peter A., additional, Byrne, Delaney M., additional, King, MacKenzie Sadie, additional, Jamieson, Amy, additional, Winn-Deen, Emily S., additional, McAlpine, Jessica N., additional, Huntsman, David, additional, Skates, Steven, additional, Huang, Eric K., additional, and Sedlak, Joseph Charles, additional

Published
2022
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25. Spartalizumab or placebo in combination with dabrafenib and trametinib in patients with $\textit{BRAF}$V600-mutant melanoma: exploratory biomarker analyses from a randomized phase 3 trial (COMBI-i)

Author

Tawbi, Hussein A, Robert, Caroline, Brase, Jan C, Gusenleitner, Daniel, Gasal, Eduard, Garrett, James, Savchenko, Alexander, Görgün, Güllü, Flaherty, Keith T, Ribas, Antoni, Dummer, Reinhard, Schadendorf, Dirk, Long, Georgina V, Nathan, Paul D, Ascierto, Paolo A, University of Zurich, and Tawbi, Hussein A

Subjects
Pharmacology, 2403 Immunology, Cancer Research, Immunology, 10177 Dermatology Clinic, 610 Medicine & health, 3004 Pharmacology, Oncology, 1313 Molecular Medicine, 2723 Immunology and Allergy, Molecular Medicine, Immunology and Allergy, 2730 Oncology, 1306 Cancer Research
Published
2022
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26. Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) ± anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies

Author

Schöffski, Patrick, primary, Tan, Daniel S W, additional, Martín, Miguel, additional, Ochoa-de-Olza, María, additional, Sarantopoulos, John, additional, Carvajal, Richard D, additional, Kyi, Chrisann, additional, Esaki, Taito, additional, Prawira, Amy, additional, Akerley, Wallace, additional, De Braud, Filippo, additional, Hui, Rina, additional, Zhang, Tian, additional, Soo, Ross A, additional, Maur, Michela, additional, Weickhardt, Andrew, additional, Krauss, Jürgen, additional, Deschler-Baier, Barbara, additional, Lau, Allen, additional, Samant, Tanay S, additional, Longmire, Tyler, additional, Chowdhury, Niladri Roy, additional, Sabatos-Peyton, Catherine A, additional, Patel, Nidhi, additional, Ramesh, Radha, additional, Hu, Tiancen, additional, Carion, Ana, additional, Gusenleitner, Daniel, additional, Yerramilli-Rao, Padmaja, additional, Askoxylakis, Vasileios, additional, Kwak, Eunice L, additional, and Hong, David S, additional

Published
2022
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27. Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib.

Author

Brase, Jan C, Brase, Jan C, Walter, Robert FH, Savchenko, Alexander, Gusenleitner, Daniel, Garrett, James, Schimming, Tobias, Varaljai, Renata, Castelletti, Deborah, Kim, Ju, Dakappagari, Naveen, Schultz, Ken, Robert, Caroline, Long, Georgina V, Nathan, Paul D, Ribas, Antoni, Flaherty, Keith T, Karaszewska, Boguslawa, Schachter, Jacob, Sucker, Antje, Schmid, Kurt W, Zimmer, Lisa, Livingstone, Elisabeth, Gasal, Eduard, Schadendorf, Dirk, Roesch, Alexander, Brase, Jan C, Brase, Jan C, Walter, Robert FH, Savchenko, Alexander, Gusenleitner, Daniel, Garrett, James, Schimming, Tobias, Varaljai, Renata, Castelletti, Deborah, Kim, Ju, Dakappagari, Naveen, Schultz, Ken, Robert, Caroline, Long, Georgina V, Nathan, Paul D, Ribas, Antoni, Flaherty, Keith T, Karaszewska, Boguslawa, Schachter, Jacob, Sucker, Antje, Schmid, Kurt W, Zimmer, Lisa, Livingstone, Elisabeth, Gasal, Eduard, Schadendorf, Dirk, and Roesch, Alexander

Abstract

PurposeAlthough patients with unresectable or metastatic melanoma can experience long-term survival with BRAF- and MEK-targeted agents or immune checkpoint inhibitors over 5 years, resistance develops in most patients. There is a distinct lack of pretherapeutic biomarkers to identify which patients are likely to benefit from each therapy type. Most research has focused on the predictive role of T cells in antitumor responses as opposed to B cells.Patients and methodsWe conducted prespecified exploratory biomarker analysis using gene expression profiling and digital pathology in 146 patients with previously untreated BRAF V600-mutant metastatic melanoma from the randomized, phase III COMBI-v trial and treated with dabrafenib plus trametinib who had available tumor specimens from screening.ResultsBaseline cell-cycle gene expression signature was associated with progression-free survival (P = 0.007). Patients with high T-cell/low B-cell gene signatures had improved median overall survival (not reached [95% confidence interval (CI), 33.8 months-not reached]) compared with patients with high T-cell/high B-cell signatures (19.1 months; 95% CI, 13.4-38.6 months). Patients with high B-cell signatures had high B-cell infiltration into the tumor compartment, corresponding with decreased MAPK activity and increased expression of immunosuppressive markers.ConclusionsB cells may serve as a potential biomarker to predict clinical outcome in patients with advanced melanoma treated with dabrafenib plus trametinib. As separate studies have shown an opposite effect for B-cell levels and response to immunotherapy, B cells may serve as a potential biomarker to facilitate treatment selection. Further validation in a larger patient cohort is needed.

Published
2021

31. 387 A Phase II, multicenter study of the safety and efficacy of LAG525 in combination with spartalizumab in patients with advanced malignancies

Author

Lin, Chia-Chi, primary, Garralda, Elena, additional, Schöffski, Patrick, additional, Hong, David, additional, Siu, Lillian, additional, Martin, Miguel, additional, Maur, Michela, additional, Hui, Rina, additional, Soo, Ross, additional, Chiu, Joanne, additional, Zhang, Tian, additional, Ma, Brigette, additional, Kyi, Chrisann, additional, Tan, Daniel, additional, Cassier, Philippe, additional, Sarantopoulos, John, additional, Weickhardt, Andrew, additional, Carvajal, Rich, additional, Spratlin, Jennifer, additional, Esaki, Taito, additional, Rolland, Fréderic, additional, Akerley, Wallace, additional, Deschler-Baier, Barbara, additional, Sabatos-Peyton, Catherine, additional, Chowdhury, Niladri Roy, additional, Gusenleitner, Daniel, additional, Kwak, Eunice, additional, Askoxylakis, Vasileios, additional, and Braud, Filippo De, additional

Published
2020
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32. Effect of first-line spartalizumab + dabrafenib + trametinib on immunosuppressive features detected in peripheral blood and clinical outcome in patients (pts) with advanced BRAF V600–mutant melanoma.

Author

Dummer, Reinhard, primary, Biette, Kelly, additional, Gusenleitner, Daniel, additional, Ramesh, Radha, additional, Lebbe, Celeste, additional, Atkinson, Victoria, additional, Mandalà, Mario, additional, Nathan, Paul D., additional, Arance, Ana, additional, Richtig, Erika, additional, Yamazaki, Naoya, additional, Robert, Caroline, additional, Schadendorf, Dirk, additional, Tawbi, Hussein Abdul-Hassan, additional, Ascierto, Paolo Antonio, additional, Ribas, Antoni, additional, Flaherty, Keith, additional, Gasal, Eduard, additional, Brase, Jan C., additional, and Long, Georgina V., additional

Published
2020
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33. Tumor microenvironment (TME), longitudinal biomarker changes, and clinical outcome in patients (pts) with advanced BRAF V600–mutant melanoma treated with first-line spartalizumab (S) + dabrafenib (D) + trametinib (T).

Author

Dummer, Reinhard, primary, Gusenleitner, Daniel, additional, Campbell, Catarina D., additional, Lebbe, Celeste, additional, Atkinson, Victoria, additional, Mandalà, Mario, additional, Nathan, Paul D., additional, Arance, Ana, additional, Richtig, Erika, additional, Yamazaki, Naoya, additional, Robert, Caroline, additional, Schadendorf, Dirk, additional, Tawbi, Hussein Abdul-Hassan, additional, Ascierto, Paolo Antonio, additional, Ribas, Antoni, additional, Flaherty, Keith, additional, Gasal, Eduard, additional, Brase, Jan C., additional, and Long, Georgina V., additional

Published
2020
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34. Additional file 1: of Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients

Author

Subrahmanyam, Priyanka, Zhiwan Dong, Gusenleitner, Daniel, Giobbie-Hurder, Anita, Severgnini, Mariano, Zhou, Jun, Manos, Michael, Eastman, Lauren, Maecker, Holden, and F. Hodi

Subjects
chemical and pharmacologic phenomena, hemic and immune systems
Abstract

Figure S1. Kaplan-Meier analysis of overall survival and progression-free survival in the anti-CTLA-4 and anti-PD-1 treated patient cohorts. Figure S2. Frequencies of major immune cell subsets in responders and non-responders to anti-CTLA-4 or anti-PD-1 therapy. Figure S3. viSNE analysis of CD45RA expression on CD4+ and CD8+ T cells in patients treated with anti-CTLA-4. Figure S4. Frequencies of memory/non-memory T cells in melanoma patients treated with anti-PD-1. Figure S5. CD69+MIP-1β+ NK cells are a distinct population. Figure S6. CD69 and MIP-1β expressing NK cells in melanoma patients treated with anti-CTLA-4. Figure S7. Frequencies of regulatory T cells in baseline PMBC from anti-CTLA-4 and anti-PD-1 treated melanoma patients. Figure S8. Baseline CTLA-4 and PD-1 expression on T cells in anti-CTLA-4 and anti-PD-1 treated patients. Figure S9. PD-L1 and PD-L2 expression in monocytes and NK cells in anti-CTLA-4 and anti-PD-1 treated melanoma patients. Figure S10. Expression of Granzyme B in NK cells and CD8+ T cells in anti-CTLA-4 and anti-PD-1 treated patients. Figure S11. A comparison of viSNE maps between pre-anti-CTLA-4 PBMC and pre-anti-PD-1 PBMC from the same patient. (DOCX 3521 kb)

Published
2018
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35. Tumor microenvironment (TME), longitudinal biomarker changes, and clinical outcome in patients (pts) with advanced BRAF V600–mutant melanoma treated with first-line spartalizumab (S) + dabrafenib (D) + trametinib (T).

Author

Dummer, Reinhard, primary, Gusenleitner, Daniel, additional, Campbell, Catarina D., additional, Lebbe, Celeste, additional, Atkinson, Victoria, additional, Mandalà, Mario, additional, Nathan, Paul D., additional, Arance, Ana, additional, Richtig, Erika, additional, Yamazaki, Naoya, additional, Robert, Caroline, additional, Schadendorf, Dirk, additional, Tawbi, Hussein Abdul-Hassan, additional, Ascierto, Paolo Antonio, additional, Ribas, Antoni, additional, Flaherty, Keith, additional, Gasal, Eduard, additional, Brase, Jan C., additional, and Long, Georgina V., additional

Published
2019
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36. GCOD - GeneChip Oncology Database

Author

Gusenleitner Daniel, Antonescu Corina, White Joseph A, Liu Fenglong, and Quackenbush John

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background DNA microarrays have become a nearly ubiquitous tool for the study of human disease, and nowhere is this more true than in cancer. With hundreds of studies and thousands of expression profiles representing the majority of human cancers completed and in public databases, the challenge has been effectively accessing and using this wealth of data. Description To address this issue we have collected published human cancer gene expression datasets generated on the Affymetrix GeneChip platform, and carefully annotated those studies with a focus on providing accurate sample annotation. To facilitate comparison between datasets, we implemented a consistent data normalization and transformation protocol and then applied stringent quality control procedures to flag low-quality assays. Conclusion The resulting resource, the GeneChip Oncology Database, is available through a publicly accessible website that provides several query options and analytical tools through an intuitive interface.

Published
2011
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37. Integrated Genetic and Topological Analysis Reveals a Hodgkin-like Mechanism of Immune Escape in T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

Author

Griffin, Gabriel K, primary, Roemer, Margaretha G.M., additional, Lipschitz, Mikel, additional, Weirather, Jason, additional, Pak, Christine J., additional, Kelly, Allysa, additional, Gusenleitner, Daniel, additional, Gjini, Evisa, additional, Chapuy, Bjoern, additional, Xu, Jie, additional, Chen, Benjamin, additional, Sohani, Aliyah R., additional, Lovitch, Scott B, additional, Fletcher, Christopher, additional, Freeman, Gordon J, additional, Hodi, Stephen, additional, Armand, Philippe, additional, Ligon, Azra H., additional, Shipp, Margaret A., additional, and Rodig, Scott J, additional

Published
2018
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38. MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma

Author

Rodig, Scott J., primary, Gusenleitner, Daniel, additional, Jackson, Donald G., additional, Gjini, Evisa, additional, Giobbie-Hurder, Anita, additional, Jin, Chelsea, additional, Chang, Han, additional, Lovitch, Scott B., additional, Horak, Christine, additional, Weber, Jeffrey S., additional, Weirather, Jason L., additional, Wolchok, Jedd D., additional, Postow, Michael A., additional, Pavlick, Anna C., additional, Chesney, Jason, additional, and Hodi, F. Stephen, additional

Published
2018
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39. Association of distinct baseline tissue biomarkers with response to nivolumab (NIVO) and ipilimumab (IPI) in melanoma: CheckMate 064.

Author

Rodig, Scott, primary, Gusenleitner, Daniel, additional, Jackson, Donald, additional, Gjini, Evisa, additional, Giobbie-Hurder, Anita, additional, Jin, Chelsea, additional, Chang, Han, additional, Lovitch, Scott, additional, Horak, Christine, additional, Weber, Jeffrey S., additional, Shipp, Margaret Ann, additional, and Hodi, F. Stephen, additional

Published
2017
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40. An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER−/PR−/Her2−Human Breast Cancer Cells

Author

Novikov, Olga, primary, Wang, Zhongyan, additional, Stanford, Elizabeth A., additional, Parks, Ashley J., additional, Ramirez-Cardenas, Alejandra, additional, Landesman, Esther, additional, Laklouk, Israa, additional, Sarita-Reyes, Carmen, additional, Gusenleitner, Daniel, additional, Li, Amy, additional, Monti, Stefano, additional, Manteiga, Sara, additional, Lee, Kyongbum, additional, and Sherr, David H., additional

Published
2016
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41. Resolving the Biological Heterogeneity of B-Cell Lymphoma, Unclassifiable, with Features Intermediate Between DLBCL and BL (BCL-U) Using Quantitative Profiles of Oncogenic Signaling Networks

Author

Carey, Christopher Daniel, primary, Gusenleitner, Daniel, additional, Xuan, Zhang, additional, Sohani, Aliyah R, additional, Weinberg, Olga, additional, Yu, Hongbo, additional, Chen, Ben, additional, Woda, Bruce, additional, Fu, Kai, additional, Monti, Stefano, additional, and Rodig, Scott J., additional

Published
2015
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42. Diffuse Large B-Cell Lymphoma Patient-Derived Xenograft Models Capture Molecular and Biologic Heterogeneity and Inform Therapy

Author

Chapuy, Bjoern, primary, Cheng, Honwei, additional, Watahiki, Akira, additional, Ducar, Matthew D, additional, Gusenleitner, Daniel, additional, Chen, Linfeng, additional, Roemer, Margaretha GM, additional, Quyang, Jing, additional, Christie, Amanda L, additional, Zhang, Liye, additional, Tan, Yuxiang, additional, Abo, Ryan P, additional, Bonin, Frederike, additional, Thorner, Aaron R, additional, Sun, Heather H., additional, Pinkus, Geraldine S, additional, van Hummelen, Paul, additional, Wulf, Gerald G, additional, Aster, Jon C, additional, Weinstock, David M, additional, Monti, Stefano, additional, Rodig, Scott J, additional, Wang, Yuzhuo, additional, and Shipp, Margaret A., additional

Published
2015
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44. In silico modeling for uncertain biochemical data

Author

Gusenleitner, Daniel

Subjects
Random Forest, Bioinformatics, Uncertain Data, Bioinformatik, Ames Test
Abstract

Analyzing and modeling data is a well established research area and a vast variety of different methods have been developed over the last decades. Most of these methods assume fixed positions of data points; only recently uncertainty in data has caught attention as potentially useful source of information. In order to provide a deeper insight into this subject, this thesis concerns itself with the following essential question: Can information on uncertainty of feature values be exploited to improve in silico modeling? For this reason a state-of-art random forest algorithm is developed using Matlab R. In addition, three techniques of handling uncertain numeric features are presented and incorporated in different modified versions of random forests. To test the hypothesis six realworld data sets were provided by AstraZeneca. The data describe biochemical features of chemical compounds, including the results of an Ames test; a widely used technique to determine the mutagenicity of chemical substances. Each of the datasets contains a single uncertain numeric feature, represented as an expected value and an error estimate. Themodified algorithms are then applied on the six data sets in order to obtain classifiers, able to predict the outcome of an Ames test. The hypothesis is tested using a paired t-test and the results reveal that information on uncertainty can indeed improve the performance of in silico models.

Published
2009

45. Actionable Genetic Features of Primary Testicular and Primary Central Nervous System Lymphomas

Author

Chapuy, Bjoern, primary, Roemer, Margaretha GM, additional, Tan, Yuxiang, additional, Stewart, Chip, additional, Zhang, Liye, additional, Dunford, Andrew J, additional, Jordanova, Ekaterina S, additional, Feuerhake, Friedrich, additional, Illerhaus, Gerald, additional, Gusenleitner, Daniel, additional, Linden, Erica, additional, Sun, Heather H, additional, Aono, Miyuki, additional, Freeman, Gordon J, additional, Golub, Todd R, additional, Getz, Gad, additional, Rodig, Scott J., additional, de Jong, Daphne, additional, Monti, Stefano, additional, and Shipp, Margaret A., additional

Published
2014
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46. Abstract 5582: A targeted molecular classifier of MYC activity and BCL-2 expression in aggressive B-cell lymphomas, designed for clinical practice

Author

Carey, Christopher D., primary, Gusenleitner, Daniel, additional, Chapuy, Bjoern, additional, Sun, Heather, additional, Ligon, Azra, additional, Kovach, Alexandra E., additional, Le, Long P., additional, Sohani, Aliyah R., additional, Shipp, Margaret, additional, Monti, Stefano, additional, and Rodig, Scott J., additional

Published
2014
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49. ASSIGN: context-specific genomic profiling of multiple heterogeneous biological pathways.

Author

Ying Shen, Rahman, Mumtahena, Piccolo, Stephen R., Gusenleitner, Daniel, El-Chaar, Nader N., Luis Cheng, Monti, Stefano, Bild, Andrea H., and Johnson, W. Evan

Subjects
BIOINFORMATICS software, GENE mapping, COMPUTER software
Abstract

Motivation: Although gene-expression signature-based biomarkers are often developed for clinical diagnosis, many promising signatures fail to replicate during validation. One major challenge is that biological samples used to generate and validate the signature are often from heterogeneous biological contexts--controlled or in vitro samples may be used to generate the signature, but patient samples may be used for validation. In addition, systematic technical biases from multiple genome-profiling platforms often mask true biological variation. Addressing such challenges will enable us to better elucidate disease mechanisms and provide improved guidance for personalized therapeutics. Results: Here, we present a pathway profiling toolkit, Adaptive Signature Selection and InteGratioN (ASSIGN), which enables robust and context-specific pathway analyses by efficiently capturing pathway activity in heterogeneous sets of samples and across profiling technologies. The ASSIGN framework is based on a flexible Bayesian factor analysis approach that allows for simultaneous profiling of multiple correlated pathways and for the adaptation of pathway signatures into specific disease. We demonstrate the robustness and versatility of ASSIGN in estimating pathway activity in simulated data, cell lines perturbed pathways and in primary tissues samples including The Cancer Genome Atlas breast carcinoma samples and liver samples exposed to genotoxic carcinogens. [ABSTRACT FROM AUTHOR]

Published
2015
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50. GCOD - GeneChip Oncology Database.

Author

Fenglong Liu, White, Joseph A., Antonescu, Corina, Gusenleitner, Daniel, and Quackenbush, John

Subjects
DNA microarrays, CANCER, GENE expression, BIOCHIPS, DATABASES, QUALITY control
Abstract

Background: DNA microarrays have become a nearly ubiquitous tool for the study of human disease, and nowhere is this more true than in cancer. With hundreds of studies and thousands of expression profiles representing the majority of human cancers completed and in public databases, the challenge has been effectively accessing and using this wealth of data. Description: To address this issue we have collected published human cancer gene expression datasets generated on the Affymetrix GeneChip platform, and carefully annotated those studies with a focus on providing accurate sample annotation. To facilitate comparison between datasets, we implemented a consistent data normalization and transformation protocol and then applied stringent quality control procedures to flag low-quality assays. Conclusion: The resulting resource, the GeneChip Oncology Database, is available through a publicly accessible website that provides several query options and analytical tools through an intuitive interface. [ABSTRACT FROM AUTHOR]

Published
2011
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