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1,311 results on '"Carbone, David P."'

1. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors

Author

Skoulidis, Ferdinandos, Araujo, Haniel A., Do, Minh Truong, Qian, Yu, Sun, Xin, Cobo, Ana Galan, Le, John T., Montesion, Meagan, Palmer, Rachael, Jahchan, Nadine, Juan, Joseph M., Min, Chengyin, Yu, Yi, Pan, Xuewen, Arbour, Kathryn C., Vokes, Natalie, Schmidt, Stephanie T., Molkentine, David, Owen, Dwight H., Memmott, Regan, Patil, Pradnya D., Marmarelis, Melina E., Awad, Mark M., Murray, Joseph C., Hellyer, Jessica A., Gainor, Justin F., Dimou, Anastasios, Bestvina, Christine M., Shu, Catherine A., Riess, Jonathan W., Blakely, Collin M., Pecot, Chad V., Mezquita, Laura, Tabbó, Fabrizio, Scheffler, Matthias, Digumarthy, Subba, Mooradian, Meghan J., Sacher, Adrian G., Lau, Sally C. M., Saltos, Andreas N., Rotow, Julia, Johnson, Rocio Perez, Liu, Corinne, Stewart, Tyler, Goldberg, Sarah B., Killam, Jonathan, Walther, Zenta, Schalper, Kurt, Davies, Kurtis D., Woodcock, Mark G., Anagnostou, Valsamo, Marrone, Kristen A., Forde, Patrick M., Ricciuti, Biagio, Venkatraman, Deepti, Van Allen, Eliezer M., Cummings, Amy L., Goldman, Jonathan W., Shaish, Hiram, Kier, Melanie, Katz, Sharyn, Aggarwal, Charu, Ni, Ying, Azok, Joseph T., Segal, Jeremy, Ritterhouse, Lauren, Neal, Joel W., Lacroix, Ludovic, Elamin, Yasir Y., Negrao, Marcelo V., Le, Xiuning, Lam, Vincent K., Lewis, Whitney E., Kemp, Haley N., Carter, Brett, Roth, Jack A., Swisher, Stephen, Lee, Richard, Zhou, Teng, Poteete, Alissa, Kong, Yifan, Takehara, Tomohiro, Paula, Alvaro Guimaraes, Parra Cuentas, Edwin R., Behrens, Carmen, Wistuba, Ignacio I., Zhang, Jianjun, Blumenschein, George R., Gay, Carl, Byers, Lauren A., Gibbons, Don L., Tsao, Anne, Lee, J. Jack, Bivona, Trever G., Camidge, D. Ross, Gray, Jhannelle E., Lieghl, Natasha, Levy, Benjamin, Brahmer, Julie R., Garassino, Marina C., Gandara, David R., Garon, Edward B., Rizvi, Naiyer A., Scagliotti, Giorgio Vittorio, Wolf, Jürgen, Planchard, David, Besse, Benjamin, Herbst, Roy S., Wakelee, Heather A., Pennell, Nathan A., Shaw, Alice T., Jänne, Pasi A., Carbone, David P., Hellmann, Matthew D., Rudin, Charles M., Albacker, Lee, Mann, Helen, Zhu, Zhou, Lai, Zhongwu, Stewart, Ross, Peters, Solange, Johnson, Melissa L., Wong, Kwok K., Huang, Alan, Winslow, Monte M., Rosen, Michael J., Winters, Ian P., Papadimitrakopoulou, Vassiliki A., Cascone, Tina, Jewsbury, Philip, and Heymach, John V.

Published
2024
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5. A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer

Author

Mason, Mike, Lapuente-Santana, Óscar, Halkola, Anni S., Wang, Wenyu, Mall, Raghvendra, Xiao, Xu, Kaufman, Jacob, Fu, Jingxin, Pfeil, Jacob, Banerjee, Jineta, Chung, Verena, Chang, Han, Chasalow, Scott D., Lin, Hung Ying, Chai, Rongrong, Yu, Thomas, Finotello, Francesca, Mirtti, Tuomas, Mäyränpää, Mikko I., Bao, Jie, Verschuren, Emmy W., Ahmed, Eiman I., Ceccarelli, Michele, Miller, Lance D., Monaco, Gianni, Hendrickx, Wouter R. L., Sherif, Shimaa, Yang, Lin, Tang, Ming, Gu, Shengqing Stan, Zhang, Wubing, Zhang, Yi, Zeng, Zexian, Das Sahu, Avinash, Liu, Yang, Yang, Wenxian, Bedognetti, Davide, Tang, Jing, Eduati, Federica, Laajala, Teemu D., Geese, William J., Guinney, Justin, Szustakowski, Joseph D., Vincent, Benjamin G., and Carbone, David P.

Published
2024
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6. A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results

Author

Rappaport, Amy R., Kyi, Chrisann, Lane, Monica, Hart, Meghan G., Johnson, Melissa L., Henick, Brian S., Liao, Chih-Yi, Mahipal, Amit, Shergill, Ardaman, Spira, Alexander I., Goldman, Jonathan W., Scallan, Ciaran D., Schenk, Desiree, Palmer, Christine D., Davis, Matthew J., Kounlavouth, Sonia, Kemp, Lindsey, Yang, Aaron, Li, Yaojun John, Likes, Molly, Shen, Annie, Boucher, Gregory R., Egorova, Milana, Veres, Robert L., Espinosa, J. Aaron, Jaroslavsky, Jason R., Kraemer Tardif, Lauren D., Acrebuche, Lindsey, Puccia, Christopher, Sousa, Leiliane, Zhou, Rita, Bae, Kyounghwa, Hecht, J. Randolph, Carbone, David P., Johnson, Benny, Allen, Andrew, Ferguson, Andrew R., and Jooss, Karin

Published
2024
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7. Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non-small cell lung cancer.

Author

Rusch, Valerie, Nicholas, Alan, Patterson, G, Waqar, Salama, Toloza, Eric, Haura, Eric, Raz, Dan, Reckamp, Karen, Merritt, Robert, Owen, Dwight, Finley, David, McNamee, Ciaran, Blasberg, Justin, Garon, Edward, Mitchell, John, Doebele, Robert, Baciewicz, Frank, Pass, Harvey, Schulze, Katja, Johnson, Ann, Bunn, Paul, Johnson, Bruce, Kris, Mark, Kwiatkowski, David, Wistuba, Ignacio, Chaft, Jamie, Carbone, David, Lee, Jay, and Nagasaka, Misako

Subjects
immunotherapy, lung cancer, neoadjuvant therapy, Aged, Female, Humans, Carcinoma, Non-Small-Cell Lung, ErbB Receptors, Immune Checkpoint Inhibitors, Lung Neoplasms, Mutation, Neoadjuvant Therapy, Receptor Protein-Tyrosine Kinases, Male, Middle Aged
Abstract

OBJECTIVE: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery. METHODS: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0. RESULTS: From April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached. CONCLUSIONS: Neoadjuvant atezolizumab in resectable stage IB to IIIB non-small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non-small cell lung cancer.

Published
2023

8. Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial.

Author

Chaft, Jamie, Oezkan, Filiz, Kris, Mark, Bunn, Paul, Wistuba, Ignacio, Kwiatkowski, David, Owen, Dwight, Tang, Yan, Johnson, Bruce, Lee, Jay, Lozanski, Gerard, Pietrzak, Maciej, Seweryn, Michal, Byun, Woo, Schulze, Katja, Nicholas, Alan, Johnson, Ann, Grindheim, Jessica, Hilz, Stephanie, Shames, David, Rivard, Chris, Toloza, Eric, Haura, Eric, McNamee, Ciaran, Patterson, G, Waqar, Saiama, Rusch, Valerie, and Carbone, David

Subjects
Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, ErbB Receptors, Humans, Lung Neoplasms, Neoadjuvant Therapy, Receptor Protein-Tyrosine Kinases, Tumor Microenvironment
Abstract

In an ongoing, open-label, single-arm phase II study ( NCT02927301 ), 181 patients with untreated, resectable, stage IB-IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14-28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches.

Published
2022

9. Five-year outcomes with first-line nivolumab plus ipilimumab with 2 cycles of chemotherapy versus 4 cycles of chemotherapy alone in patients with metastatic non-small cell lung cancer in the randomized CheckMate 9LA trial

Author

Reck, Martin, Ciuleanu, Tudor-Eliade, Schenker, Michael, Bordenave, Stephanie, Cobo, Manuel, Juan-Vidal, Oscar, Reinmuth, Niels, Richardet, Eduardo, Felip, Enriqueta, Menezes, Juliana, Cheng, Ying, Mizutani, Hideaki, Zurawski, Bogdan, Alexandru, Aurelia, Carbone, David P., Lu, Shun, John, Thomas, Aoyama, Takekazu, Grootendorst, Diederik J., Hu, Nan, Eccles, Laura J., and Paz-Ares, Luis G.

Published
2024
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10. Resiliency among older adults receiving lung cancer treatment (ROAR-LCT): A novel supportive care intervention for older adults with advanced lung cancer

Author

Presley, Carolyn J., Grogan, Madison, Compston, Amy, Hock, Karen, Knauss, Brittany, Redder, Elyse, Arrato, Nicole A., Lo, Stephen B., Janse, Sarah, Benedict, Jason, Hoyd, Rebecca, Williams, Nyelia, Hayes, Scott, Wells-Di Gregorio, Sharla, Gill, Thomas M., Allore, Heather, Focht, Brian, Quist, Morten, Carbone, David P., Spakowicz, Daniel, Paskett, Electra D., and Andersen, Barbara L.

Published
2024
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11. TSAFinder: exhaustive tumor-specific antigen detection with RNAseq.

Author

Sharpnack, Michael, Johnson, Travis, Han, Zhi, Carbone, David, Huang, Kun, He, Kai, and Chalkley, Robert

Subjects
Animals, Humans, Mice, Adenocarcinoma of Lung, Antigens, Neoplasm, Lung Neoplasms, Peptides, RNA, Sequence Analysis, RNA
Abstract

MOTIVATION: Tumor-specific antigen (TSA) identification in human cancer predicts response to immunotherapy and provides targets for cancer vaccine and adoptive T-cell therapies with curative potential, and TSAs that are highly expressed at the RNA level are more likely to be presented on major histocompatibility complex (MHC)-I. Direct measurements of the RNA expression of peptides would allow for generalized prediction of TSAs. Human leukocyte antigen (HLA)-I genotypes were predicted with seq2HLA. RNA sequencing (RNAseq) fastq files were translated into all possible peptides of length 8-11, and peptides with high and low expressions in the tumor and control samples, respectively, were tested for their MHC-I binding potential with netMHCpan-4.0. RESULTS: A novel pipeline for TSA prediction from RNAseq was used to predict all possible unique peptides size 8-11 on previously published murine and human lung and lymphoma tumors and validated on matched tumor and control lung adenocarcinoma (LUAD) samples. We show that neoantigens predicted by exomeSeq are typically poorly expressed at the RNA level, and a fraction is expressed in matched normal samples. TSAs presented in the proteomics data have higher RNA abundance and lower MHC-I binding percentile, and these attributes are used to discover high confidence TSAs within the validation cohort. Finally, a subset of these high confidence TSAs is expressed in a majority of LUAD tumors and represents attractive vaccine targets. AVAILABILITY AND IMPLEMENTATION: The datasets were derived from sources in the public domain as follows: TSAFinder is open-source software written in python and R. It is licensed under CC-BY-NC-SA and can be downloaded at https://github.com/RNAseqTSA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Published
2022

12. Mean platelet volume, thrombocytosis, and survival in non-small cell lung cancer patients treated with first-line pembrolizumab alone or with chemotherapy

Author

Li, Mingjia, Zhao, Songzhu, Lopez, Gabrielle, Secor, Austin, Das, Parthib, Surya, Nitya, Grogan, Madison, Patel, Sandip, Chakravarthy, Karthik, Miah, Abdul, Spakowicz, Daniel, Tinoco, Gabriel, Li, Zihai, Wei, Lai, He, Kai, Bertino, Erin, Alahmadi, Asrar, Memmott, Regan, Kaufman, Jacob, Shields, Peter G., Carbone, David P., Presley, Carolyn J., Otterson, Gregory A., and Owen, Dwight H.

Published
2023
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14. Artificial Intelligence–Powered Assessment of Pathologic Response to Neoadjuvant Atezolizumab in Patients With NSCLC: Results From the LCMC3 Study

Author

Dacic, Sanja, Travis, William D., Giltnane, Jennifer M., Kos, Filip, Abel, John, Hilz, Stephanie, Fujimoto, Junya, Sholl, Lynette, Ritter, Jon, Khalil, Farah, Liu, Yi, Taylor-Weiner, Amaro, Resnick, Murray, Yu, Hui, Hirsch, Fred R., Bunn, Paul A., Jr., Carbone, David P., Rusch, Valerie, Kwiatkowski, David J., Johnson, Bruce E., Lee, Jay M., Hennek, Stephanie R., Wapinski, Ilan, Nicholas, Alan, Johnson, Ann, Schulze, Katja, Kris, Mark G., and Wistuba, Ignacio I.

Published
2024
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15. Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer

Author

Christopoulos, Petros, Harel, Michal, McGregor, Kimberly, Brody, Yehuda, Puzanov, Igor, Bar, Jair, Elon, Yehonatan, Sela, Itamar, Yellin, Ben, Lahav, Coren, Raveh, Shani, Reiner-Benaim, Anat, Reinmuth, Niels, Nechushtan, Hovav, Farrugia, David, Bustinza-Linares, Ernesto, Lou, Yanyan, Leibowitz, Raya, Kamer, Iris, Zer Kuch, Alona, Moskovitz, Mor, Levy-Barda, Adva, Koch, Ina, Lotem, Michal, Katzenelson, Rivka, Agbarya, Abed, Price, Gillian, Cheley, Helen, Abu-Amna, Mahmoud, Geldart, Tom, Gottfried, Maya, Tepper, Ella, Polychronis, Andreas, Wolf, Ido, Dicker, Adam P., Carbone, David P., and Gandara, David R.

Published
2024
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16. Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis.

Author

Wang, Victoria E, Blaser, Bradley W, Patel, Ravi K, Behbehani, Gregory K, Rao, Arjun A, Durbin-Johnson, Blythe, Jiang, Tommy, Logan, Aaron C, Settles, Matthew, Mannis, Gabriel N, Olin, Rebecca, Damon, Lloyd E, Martin, Thomas G, Sayre, Peter H, Gaensler, Karin M, McMahon, Emma, Flanders, Michael, Weinberg, Vivian, Ye, Chun J, Carbone, David P, Munster, Pamela N, Fragiadakis, Gabriela K, McCormick, Frank, and Andreadis, Charalambos

Subjects
Humans, Antineoplastic Combined Chemotherapy Protocols, Antibodies, Monoclonal, Prospective Studies, Proteomics, Leukemia, Myeloid, Acute, CyTOF, MET, ficlatuzumab, refractory AML, single cell RNA sequencing, Hematology, Cancer, Rare Diseases, Clinical Research, Pediatric, Childhood Leukemia, Pediatric Cancer, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions
Abstract

Acute myeloid leukemia patients refractory to induction therapy or relapsed within one year have poor outcomes. Autocrine production of hepatocyte growth factor by myeloid blasts drives leukemogenesis in pre-clinical models. A phase Ib trial evaluated ficlatuzumab, a first-in-class anti-HGF antibody, in combination with cytarabine in this high-risk population. Dose-limiting toxicities were not observed, and 20 mg/kg was established as the recommended phase II dose. The most frequent treatment-related adverse event was febrile neutropenia. Among 17 evaluable patients, the overall response rate was 53%, all complete remissions. Phospho-proteomic mass cytometry showed potent on-target suppression of p-MET after ficlatuzumab treatment and that attenuation of p-S6 was associated with clinical response. Multiplexed single cell RNA sequencing using prospectively acquired patient specimens identified interferon response genes as adverse predictive factors. The ficlatuzumab and cytarabine combination is well-tolerated with favorable efficacy. High-dimensional analyses at single-cell resolution represent promising approaches for identifying biomarkers of response and mechanisms of resistance in prospective clinical studies.

Published
2021

17. Long-Term Survival Outcomes With First-Line Nivolumab Plus Ipilimumab–Based Treatment in Patients With Metastatic NSCLC and Tumor Programmed Death-Ligand 1 Lower Than 1%: A Pooled Analysis

Author

Peters, Solange, Paz-Ares, Luis G., Reck, Martin, Carbone, David P., Brahmer, Julie R., Borghaei, Hossein, Lu, Shun, O’Byrne, Kenneth J., John, Thomas, Ciuleanu, Tudor-Eliade, Schenker, Michael, Bernabe Caro, Reyes, Nishio, Makoto, Cobo, Manuel, Lee, Jong-Seok, Zurawski, Bogdan, Pluzanski, Adam, Aoyama, Takekazu, Tschaika, Marina, Devas, Vipul, Grootendorst, Diederik J., and Ramalingam, Suresh S.

Published
2024
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18. International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy

Author

Dacic, Sanja, Travis, William, Redman, Mary, Saqi, Anjali, Cooper, Wendy A., Borczuk, Alain, Chung, Jin-Haeng, Glass, Carolyn, Lopez, Javier Martin, Roden, Anja C., Sholl, Lynette, Weissferdt, Annikka, Posadas, Juan, Walker, Angela, Zhu, Hu, Wijeratne, Manuja T., Connolly, Casey, Wynes, Murry, Bota-Rabassedas, Neus, Sanchez-Espiridion, Beatriz, Lee, J.Jack, Berezowska, Sabina, Chou, Teh-Ying, Kerr, Keith, Nicholson, Andrew, Poleri, Claudia, Schalper, Kurt A., Tsao, Ming-Sound, Carbone, David P., Ready, Neal, Cascone, Tina, Heymach, John, Sepesi, Boris, Shu, Catherine, Rizvi, Naiyer, Sonett, Josuha, Altorki, Nasser, Provencio, Mariano, Bunn, Paul A., Jr., Kris, Mark G., Belani, Chandra P., Kelly, Karen, and Wistuba, Ignacio

Published
2023
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19. Author Correction: Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial

Author

Chaft, Jamie E., Oezkan, Filiz, Kris, Mark G., Bunn, Paul A., Wistuba, Ignacio I., Kwiatkowski, David J., Owen, Dwight H., Tang, Yan, Johnson, Bruce E., Lee, Jay M., Lozanski, Gerard, Pietrzak, Maciej, Seweryn, Michal, Byun, Woo Yul, Schulze, Katja, Nicholas, Alan, Johnson, Ann, Grindheim, Jessica, Hilz, Stephanie, Shames, David S., Rivard, Chris, Toloza, Eric, Haura, Eric B., McNamee, Ciaran J., Patterson, G. Alexander, Waqar, Saiama N., Rusch, Valerie W., and Carbone, David P.

Published
2024
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21. Adaptive Resistance to Dual BRAF/MEK Inhibition in BRAF-Driven Tumors through Autocrine FGFR Pathway Activation.

Author

Wang, Victoria E, Xue, Jenny Y, Frederick, Dennie T, Cao, Yi, Lin, Eva, Wilson, Catherine, Urisman, Anatoly, Carbone, David P, Flaherty, Keith T, Bernards, Rene, Lito, Piro, Settleman, Jeff, and McCormick, Frank

Subjects
Tumor Cells, Cultured, Animals, Humans, Mice, Mice, Nude, Melanoma, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Proto-Oncogene Proteins B-raf, MAP Kinase Kinase 1, Fibroblast Growth Factor 1, Antineoplastic Agents, Prognosis, Survival Rate, Xenograft Model Antitumor Assays, Autocrine Communication, Apoptosis, Cell Proliferation, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Receptor, Fibroblast Growth Factor, Type 1, High-Throughput Screening Assays, Biomarkers, Tumor, Clinical Research, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeCombined MAPK pathway inhibition using dual BRAF and MEK inhibitors has prolonged the duration of clinical response in patients with BRAFV600E-driven tumors compared with either agent alone. However, resistance frequently arises.Experimental designWe generated cell lines resistant to dual BRAF/MEK inhibition and utilized a pharmacologic synthetic lethal approach to identify a novel, adaptive resistance mechanism mediated through the fibroblast growth factor receptor (FGFR) pathway.ResultsIn response to drug treatment, transcriptional upregulation of FGF1 results in autocrine activation of FGFR, which potentiates extracellular signal-regulated kinases (ERK) activation. FGFR inhibition overcomes resistance to dual BRAF/MEK inhibitors in both cell lines and patient-derived xenograft (PDX) models. Abrogation of this bypass mechanism in the first-line setting enhances tumor killing and prevents the emergence of drug-resistant cells. Moreover, clinical data implicate serum FGF1 levels in disease prognosis.ConclusionsTaken together, these results describe a new, adaptive resistance mechanism that is more commonly observed in the context of dual BRAF/MEK blockade as opposed to single-agent treatment and reveal the potential clinical utility of FGFR-targeting agents in combination with BRAF and MEK inhibitors as a promising strategy to forestall resistance in a subset of BRAF-driven cancers.

Published
2019

23. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in metastatic non-small cell lung cancer: CheckMate 9LA 2-year patient-reported outcomes

Author

Reck, Martin, Ciuleanu, Tudor-Eliade, Cobo, Manuel, Schenker, Michael, Zurawski, Bogdan, Menezes, Juliana, Richardet, Eduardo, Bennouna, Jaafar, Felip, Enriqueta, Juan-Vidal, Oscar, Alexandru, Aurelia, Cheng, Ying, Sakai, Hiroshi, Paz-Ares, Luis, Lu, Shun, John, Thomas, Sun, Xiaowu, Moisei, Aniela, Taylor, Fiona, Lawrance, Rachael, Zhang, Xiaoqing, Sylvester, Judi, Yuan, Yong, Blum, Steven I., Penrod, John R., and Carbone, David P.

Published
2023
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25. First-Line Nivolumab Plus Ipilimumab With Chemotherapy Versus Chemotherapy Alone for Metastatic NSCLC in CheckMate 9LA: 3-Year Clinical Update and Outcomes in Patients With Brain Metastases or Select Somatic Mutations

Author

Paz-Ares, Luis G., Ciuleanu, Tudor-Eliade, Cobo, Manuel, Bennouna, Jaafar, Schenker, Michael, Cheng, Ying, Juan-Vidal, Oscar, Mizutani, Hideaki, Lingua, Alejo, Reyes-Cosmelli, Felipe, Reinmuth, Niels, Menezes, Juliana, Jassem, Jacek, Protsenko, Svetlana, Richardet, Eduardo, Felip, Enriqueta, Feeney, Kynan, Zurawski, Bogdan, Alexandru, Aurelia, de la Mora Jimenez, Emmanuel, Dakhil, Shaker, Lu, Shun, Reck, Martin, John, Thomas, Hu, Nan, Zhang, Xiaoqing, Sylvester, Judi, Eccles, Laura J., Grootendorst, Diederik J., Balli, David, Neely, Jaclyn, and Carbone, David P.

Published
2023
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26. Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results

Author

Palmer, Christine D., Rappaport, Amy R., Davis, Matthew J., Hart, Meghan G., Scallan, Ciaran D., Hong, Sue-Jean, Gitlin, Leonid, Kraemer, Lauren D., Kounlavouth, Sonia, Yang, Aaron, Smith, Lindsey, Schenk, Desiree, Skoberne, Mojca, Taquechel, Kiara, Marrali, Martina, Jaroslavsky, Jason R., Nganje, Charmaine N., Maloney, Elizabeth, Zhou, Rita, Navarro-Gomez, Daniel, Greene, Adrienne C., Grotenbreg, Gijsbert, Greer, Renee, Blair, Wade, Cao, Minh Duc, Chan, Shawn, Bae, Kyounghwa, Spira, Alexander I., Roychowdhury, Sameek, Carbone, David P., Henick, Brian S., Drake, Charles G., Solomon, Benjamin J., Ahn, Daniel H., Mahipal, Amit, Maron, Steve B., Johnson, Benny, Rousseau, Raphael, Yelensky, Roman, Liao, Chih-Yi, Catenacci, Daniel V. T., Allen, Andrew, Ferguson, Andrew R., and Jooss, Karin

Published
2022
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28. Serum Albumin: Early Prognostic Marker of Benefit for Immune Checkpoint Inhibitor Monotherapy But Not Chemoimmunotherapy

Author

Guo, Yizhen, Wei, Lai, Patel, Sandip H., Lopez, Gabrielle, Grogan, Madison, Li, Mingjia, Haddad, Tyler, Johns, Andrew, Ganesan, Latha P., Yang, Yiping, Spakowicz, Daniel J., Shields, Peter G., He, Kai, Bertino, Erin M., Otterson, Gregory A., Carbone, David P., Presley, Carolyn, Kulp, Samuel K., Mace, Thomas A., Coss, Christopher C., Phelps, Mitch A., and Owen, Dwight H.

Published
2022
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29. Homologous recombination deficiency (HRD) can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients

Author

Zhou, Zhen, Ding, Zhengping, Yuan, Jie, Shen, Shengping, Jian, Hong, Tan, Qiang, Yang, Yunhai, Chen, Zhiwei, Luo, Qingquan, Cheng, Xinghua, Yu, Yongfeng, Niu, Xiaomin, Qian, Liqiang, Chen, Xiaoke, Gu, Linping, Liu, Ruijun, Ma, Shenglin, Huang, Jia, Chen, Tianxiang, Li, Ziming, Ji, Wenxiang, Song, Liwei, Shen, Lan, Jiang, Long, Yu, Zicheng, Zhang, Chao, Tai, Zaixian, Wang, Changxi, Chen, Rongrong, Carbone, David P., Xia, Xuefeng, and Lu, Shun

Published
2022
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30. Retraction Note: AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing

Author

Laliotis, Georgios I., Chavdoula, Evangelia, Paraskevopoulou, Maria D., Kaba, Abdul, La Ferlita, Alessandro, Singh, Satishkumar, Anastas, Vollter, Nair, II, Keith A., Orlacchio, Arturo, Taraslia, Vasiliki, Vlachos, Ioannis, Capece, Marina, Hatzigeorgiou, Artemis, Palmieri, Dario, Tsatsanis, Christos, Alaimo, Salvatore, Sehgal, Lalit, Carbone, David P., Coppola, Vincenzo, and Tsichlis, Philip N.

Published
2022
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31. Atezolizumab Before and After Chemoradiation for Unresectable Stage III Non–Small Cell Lung Cancer: A Phase II Nonrandomized Controlled Trial.

Author

Ross, Helen J., Kozono, David, Wang, Xiaofei F., Urbanic, James John, Williams, Terence M., Nelson, Garth D., Carbone, David P., Chung, Dongjun, Robb, Ryan, Byun, Woo Yul, Talabere, Tiffany, DuFrane, Carter, Bara, Ilze, Schulze, Katja, Brockman, Michelle, Gao, Junheng, Vokes, Everett E., and Stinchcombe, Thomas E.

Published
2024
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33. An in vivo 'turning model' reveals new RanBP9 interactions in lung macrophages.

Author

Kajimura, Yasuko, primary, Tessari, Anna, additional, Orlacchio, Arturo, additional, Thoms, Alexandra, additional, Cufaro, Maria Concetta, additional, Di Marco, Federica, additional, Amari, Foued, additional, Chen, Min, additional, Soliman, Shimaa S.H., additional, Rizzotto, Lara, additional, Zhang, Liwen, additional, Amann, Joseph, additional, Carbone, David P, additional, Ahmed, Amer, additional, Fiermonte, Giuseppe, additional, Freitas, Mike, additional, Lodi, Alessia, additional, Del Boccio, Piero, additional, Palmieri, Dario, additional, and Coppola, Vincenzo, additional

Published
2024
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38. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial

Author

Neal, Joel W, Dahlberg, Suzanne E, Wakelee, Heather A, Aisner, Seena C, Bowden, Michaela, Huang, Ying, Carbone, David P, Gerstner, Gregory J, Lerner, Rachel E, Rubin, Jerome L, Owonikoko, Taofeek K, Stella, Philip J, Steen, Preston D, Khalid, Ahmed Ali, Ramalingam, Suresh S, and Investigators, ECOG-ACRIN 1512

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Trials and Supportive Activities, Clinical Research, Lung, Lung Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Anilides, Carcinoma, Non-Small-Cell Lung, ErbB Receptors, Erlotinib Hydrochloride, Female, Humans, Lung Neoplasms, Male, Middle Aged, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-met, Pyridines, ECOG-ACRIN 1512 Investigators, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundErlotinib is approved for the treatment of all patients with advanced non-small-cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We compared the efficacy of cabozantinib alone or in combination with erlotinib versus erlotinib alone in patients with EGFR wild-type NSCLC.MethodsThis three group, randomised, controlled, open-label, multicentre, phase 2 trial was done in 37 academic and community oncology practices in the USA. Patients were eligible if they had received one or two previous treatments for advanced non-squamous, EGFR wild-type, NSCLC. Patients were stratified by performance status and line of therapy, and randomly assigned using permuted blocks within strata to receive open-label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was done every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single-drug group to receive combination treatment. The primary endpoint was to compare progression-free survival in patients given erlotinib alone versus cabozantinib alone, and in patients given erlotinib alone versus the combination of erlotinib plus cabozantinib. We assessed the primary endpoint in the per-protocol population, which was defined as all patients who were eligible, randomly assigned, and received at least one dose of treatment. The safety analysis population included all patients who received study treatment irrespective of eligibility. This trial is registered with ClinicalTrials.gov, number NCT01708954.FindingsBetween Feb 7, 2013, and July 1, 2014, we enrolled and randomly assigned 42 patients to erlotinib treatment, 40 patients to cabozantinib treatment, and 43 patients to erlotinib plus cabozantinib treatment, of whom 111 (89%) in total were included in the primary analysis (erlotinib [n=38], cabozantinib [n=38], erlotinib plus cabozantinib [n=35]). Compared with erlotinib alone (median 1·8 months [95% CI 1·7-2·2]), progression-free survival was significantly improved in the cabozantinib group (4·3 months [3·6-7·4]; hazard ratio [HR] 0·39, 80% CI 0·27-0·55; one-sided p=0·0003) and in the erlotinib plus cabozantinib group (4·7 months [2·4-7·4]; HR 0·37, 0·25-0·53; one-sided p=0·0003). Among participants included in the safety analysis of the erlotinib (n=40), cabozantinib (n=40), and erlotinib plus cabozantinib (n=39) groups, the most common grade 3 or 4 adverse events were diarrhoea (three [8%] cases in the erlotinib group vs three [8%] in the cabozantinib group vs 11 [28%] in the erlotinib plus cabozantinib group), hypertension (none vs ten [25%] vs one [3%]), fatigue (five [13%] vs six [15%] vs six [15%]), oral mucositis (none vs four [10%] vs one [3%]), and thromboembolic event (none vs three [8%] vs two [5%]). One death due to respiratory failure occurred in the cabozantinib group, deemed possibly related to either drug, and one death due to pneumonitis occurred in the erlotinib plus cabozantinib group, deemed related to either drug or the combination.InterpretationDespite its small sample size, this trial showed that, in patients with EGFR wild-type NSCLC, cabozantinib alone or combined with erlotinib has clinically meaningful, superior efficacy to that of erlotinib alone, with additional toxicity that was generally manageable. Cabozantinib-based regimens are promising for further investigation in this patient population.FundingECOG-ACRIN Cancer Research Group, National Cancer Institute of the National Institutes of Health.

Published
2016

39. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial

Author

Paz-Ares, Luis, Ciuleanu, Tudor-Eliade, Cobo, Manuel, Schenker, Michael, Zurawski, Bogdan, Menezes, Juliana, Richardet, Eduardo, Bennouna, Jaafar, Felip, Enriqueta, Juan-Vidal, Oscar, Alexandru, Aurelia, Sakai, Hiroshi, Lingua, Alejo, Salman, Pamela, Souquet, Pierre-Jean, De Marchi, Pedro, Martin, Claudio, Pérol, Maurice, Scherpereel, Arnaud, Lu, Shun, John, Thomas, Carbone, David P, Meadows-Shropshire, Stephanie, Agrawal, Shruti, Oukessou, Abderrahim, Yan, Jinchun, and Reck, Martin

Published
2021
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40. Phase II Study of Immunotherapy With Tecemotide and Bevacizumab After Chemoradiation in Patients With Unresectable Stage III Non-Squamous Non–Small-Cell Lung Cancer (NS-NSCLC): A Trial of the ECOG-ACRIN Cancer Research Group (E6508)

Author

Patel, Jyoti D., Lee, Ju-Whei, Carbone, David P., Wagner, Henry, Shanker, Anil, de Aquino, Maria Teresa P., Horn, Leora, Johnson, Melissa L., Gerber, David E., Liu, Jane Jijun, Das, Millie S., Al-Nsour, Mohammed Ali, Dakhil, Christopher S.R., Ramalingam, Suresh, and Schiller, Joan H.

Published
2020
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41. The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016.

Author

Tan, Daniel SW, Yom, Sue S, Tsao, Ming S, Pass, Harvey I, Kelly, Karen, Peled, Nir, Yung, Rex C, Wistuba, Ignacio I, Yatabe, Yasushi, Unger, Michael, Mack, Philip C, Wynes, Murry W, Mitsudomi, Tetsuya, Weder, Walter, Yankelevitz, David, Herbst, Roy S, Gandara, David R, Carbone, David P, Bunn, Paul A, Mok, Tony SK, and Hirsch, Fred R

Subjects
Humans, Carcinoma, Non-Small-Cell Lung, Brain Neoplasms, Lung Neoplasms, Protein Kinase Inhibitors, Consensus, Drug Resistance, Neoplasm, Mutation, ErbB Receptors, Brain metastases, EGFR mutation, Non–small cell lung cancer, Resistance, Therapy, Tyrosine kinase inhibitor, Non-small cell lung cancer, Carcinoma, Non-Small-Cell Lung, Drug Resistance, Neoplasm, Receptor, Epidermal Growth Factor, Lung Cancer, Lung, Cancer, Clinical Research, Oncology & Carcinogenesis, Clinical Sciences, Cardiorespiratory Medicine and Haematology, Oncology and Carcinogenesis
Abstract

Mutations in the epidermal growth factor receptor gene (EGFR) represent one of the most frequent "actionable" alterations in non-small cell lung cancer (NSCLC). Typified by high response rates to targeted therapies, EGFR tyrosine kinase inhibitors (TKIs) are now established first-line treatment options and have transformed the treatment paradigm for NSCLC. With the recent breakthrough designation and approval of the third-generation EGFR TKI osimertinib, available systemic and local treatment options have expanded, requiring new clinical algorithms that take into account individual patient molecular and clinical profiles. In this International Association for the Study of Lung Cancer commissioned consensus statement, key pathologic, diagnostic, and therapeutic considerations, such as optimal choice of EGFR TKI and management of brain metastasis, are discussed. In addition, recommendations are made for clinical guidelines and research priorities, such as the role of repeat biopsies and use of circulating free DNA for molecular studies. With the rapid pace of progress in treating EGFR-mutant NSCLC, this statement provides a state-of-the-art review of the contemporary issues in managing this unique subgroup of patients.

Published
2016

42. Artificial intelligence–powered assessment of pathologic response to neoadjuvant atezolizumab in patients with non-small cell lung cancer: results from the LCMC3 study

Author

Dacic, Sanja, primary, Travis, William D., additional, Giltnane, Jennifer M., additional, Kos, Filip, additional, Abel, John, additional, Hilz, Stephanie, additional, Fujimoto, Junya, additional, Sholl, Lynette, additional, Ritter, Jon, additional, Khalil, Farah, additional, Liu, Yi, additional, Taylor-Weiner, Amaro, additional, Resnick, Murray, additional, Yu, Hui, additional, Hirsch, Fred R., additional, Bunn, Paul A., additional, Carbone, David P., additional, Rusch, Valerie, additional, Kwiatkowski, David J., additional, Johnson, Bruce E., additional, Lee, Jay M., additional, Hennek, Stephanie R., additional, Wapinski, Ilan, additional, Nicholas, Alan, additional, Johnson, Ann, additional, Schulze, Katja, additional, Kris, Mark G., additional, and Wistuba, Ignacio I., additional

Published
2023
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44. RETRACTED ARTICLE: AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing

Author

Laliotis, Georgios I., Chavdoula, Evangelia, Paraskevopoulou, Maria D., Kaba, Abdul, La Ferlita, Alessandro, Singh, Satishkumar, Anastas, Vollter, Nair, II, Keith A., Orlacchio, Arturo, Taraslia, Vasiliki, Vlachos, Ioannis, Capece, Marina, Hatzigeorgiou, Artemis, Palmieri, Dario, Tsatsanis, Christos, Alaimo, Salvatore, Sehgal, Lalit, Carbone, David P., Coppola, Vincenzo, and Tsichlis, Philip N.

Published
2021
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47. Notch in Lung Cancer

Author

Sinicropi-Yao, Sara L., Koenig, Michael J., Carbone, David P., Miele, Lucio, editor, and Artavanis-Tsakonas, Spyros, editor

Published
2018
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