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229 results on '"Rubin, Eric H"'

2. Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors

Author

Moschos, Stergios J, Sullivan, Ryan J, Hwu, Wen-Jen, Ramanathan, Ramesh K, Adjei, Alex A, Fong, Peter C, Shapira-Frommer, Ronnie, Tawbi, Hussein A, Rubino, Joseph, Rush, Thomas S, Zhang, Da, Miselis, Nathan R, Samatar, Ahmed A, Chun, Patrick, Rubin, Eric H, Schiller, James, Long, Brian J, Dayananth, Priya, Carr, Donna, Kirschmeier, Paul, Bishop, W Robert, Deng, Yongqi, Cooper, Alan, Shipps, Gerald W, Moreno, Blanca Homet, Robert, Lidia, Ribas, Antoni, and Flaherty, Keith T

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Cancer, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Administration, Oral, Adult, Animals, Biological Availability, Cell Line, Tumor, Diarrhea, Dogs, Dose-Response Relationship, Drug, Drug Eruptions, Drug Evaluation, Preclinical, Fatigue, Female, Humans, Indazoles, MAP Kinase Signaling System, Male, Maximum Tolerated Dose, Mice, Middle Aged, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Nausea, Neoplasm Staging, Neoplasms, Protein Kinase Inhibitors, Pyridines, Pyrrolidines, Rats, Triazoles, Xenograft Model Antitumor Assays, Young Adult, Clinical Trials, Melanoma, Oncology, Signal transduction, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundConstitutive activation of ERK1/2 occurs in various cancers, and its reactivation is a well-described resistance mechanism to MAPK inhibitors. ERK inhibitors may overcome the limitations of MAPK inhibitor blockade. The dual mechanism inhibitor SCH772984 has shown promising preclinical activity across various BRAFV600/RAS-mutant cancer cell lines and human cancer xenografts.MethodsWe have developed an orally bioavailable ERK inhibitor, MK-8353; conducted preclinical studies to demonstrate activity, pharmacodynamic endpoints, dosing, and schedule; completed a study in healthy volunteers (P07652); and subsequently performed a phase I clinical trial in patients with advanced solid tumors (MK-8353-001). In the P07652 study, MK-8353 was administered as a single dose in 10- to 400-mg dose cohorts, whereas in the MK-8353-001 study, MK-8353 was administered in 100- to 800-mg dose cohorts orally twice daily. Safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity were analyzed.ResultsMK-8353 exhibited comparable potency with SCH772984 across various preclinical cancer models. Forty-eight patients were enrolled in the P07652 study, and twenty-six patients were enrolled in the MK-8353-001 study. Adverse events included diarrhea (44%), fatigue (40%), nausea (32%), and rash (28%). Dose-limiting toxicity was observed in the 400-mg and 800-mg dose cohorts. Sufficient exposure to MK-8353 was noted that correlated with biological activity in preclinical data. Three of fifteen patients evaluable for treatment response in the MK-8353-001 study had partial response, all with BRAFV600-mutant melanomas.ConclusionMK-8353 was well tolerated up to 400 mg twice daily and exhibited antitumor activity in patients with BRAFV600-mutant melanoma. However, antitumor activity was not particularly correlated with pharmacodynamic parameters.Trial registrationClinicalTrials.gov NCT01358331.FundingMerck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., and NIH (P01 CA168585 and R35 CA197633).

Published
2018

3. From Famine to Feast: Developing Early-Phase Combination Immunotherapy Trials Wisely

Author

Day, Daphne, Monjazeb, Arta M, Sharon, Elad, Ivy, S Percy, Rubin, Eric H, Rosner, Gary L, and Butler, Marcus O

Subjects
Clinical Research, Cancer, Vaccine Related, Clinical Trials and Supportive Activities, Immunization, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Clinical Trials as Topic, Combined Modality Therapy, Humans, Immunotherapy, Neoplasms, Treatment Outcome, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Not until the turn of this century has immunotherapy become a fundamental component of cancer treatment. While monotherapy with immune modulators, such as immune checkpoint inhibitors, provides a subset of patients with durable clinical benefit and possible cure, combination therapy offers the potential for antitumor activity in a greater number of patients. The field of immunology has provided us with a plethora of potential molecules and pathways to target. This abundance makes it impractical to empirically test all possible combinations efficiently. We recommend that potential immunotherapy combinations be chosen based on sound rationale and available data to address the mechanisms of primary and acquired immune resistance. Novel trial designs may increase the proportion of patients receiving potentially efficacious treatments and, at the same time, better define the balance of clinical activity and safety. We believe that implementing a strategic approach in the early development of immunotherapy combinations will expedite the delivery of more effective therapies with improved safety and durable outcomes.

Published
2017

4. Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit

Author

Hayes, Daniel F., Herbst, Roy S., Myles, Jonathan L., Topalian, Suzanne L., Yohe, Sophia L., Aronson, Naomi, Bellizzi, Andrew M., Basu Roy, Upal, Bradshaw, Georganne, Edwards, Robin H., El-Gabry, Ehab A., Elvin, Julia, Gajewski, Thomas F., McShane, Lisa M., Oberley, Matthew, Philip, Reena, Rimm, David L., Rosenbaum, Jason N., Rubin, Eric H., Schlager, Lisa, Sherwood, Shimere W., Stewart, Mark, Taube, Janis M., Thurin, Magdalena, Vasalos, Patricia, and Laser, Jordan

Published
2022
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5. Informing the Tolerability of Cancer Treatments Using Patient-Reported Outcome Measures: Summary of an FDA and Critical Path Institute Workshop

Author

Kluetz, Paul G., Kanapuru, Bindu, Lemery, Steven, Johnson, Laura Lee, Fiero, Mallorie H., Arscott, Karen, Barbachano, Yolanda, Basch, Ethan, Campbell, Michelle, Cappelleri, Joseph C., Cella, David, Cleeland, Charles, Coens, Corneel, Daniels, Selena, Denlinger, Crystal S., Fairclough, Dianne L., Hillard, James R., Minasian, Lori, Mitchell, Sandra A., O’Connor, Daniel, Patel, Sheetal, Rubin, Eric H., Ryden, Anna, Soltys, Katherine, Sridhara, Rajeshwari, Thanarajasingam, Gita, Velikova, Galina, and Coons, Stephen Joel

Published
2018
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6. Supplementary material and tables from A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer

Author

Oza, Amit M., primary, Estevez-Diz, Maria, primary, Grischke, Eva-Maria, primary, Hall, Marcia, primary, Marmé, Frederik, primary, Provencher, Diane, primary, Uyar, Denise, primary, Weberpals, Johanne I., primary, Wenham, Robert M., primary, Laing, Naomi, primary, Tracy, Michael, primary, Freshwater, Tomoko, primary, Lee, Mark A., primary, Liu, Ji, primary, Qiu, Jingjun, primary, Rose, Shelonitda, primary, Rubin, Eric H., primary, and Moore, Kathleen, primary

Published
2023
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7. Supplementary Figure 3 from A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer

Author

Oza, Amit M., primary, Estevez-Diz, Maria, primary, Grischke, Eva-Maria, primary, Hall, Marcia, primary, Marmé, Frederik, primary, Provencher, Diane, primary, Uyar, Denise, primary, Weberpals, Johanne I., primary, Wenham, Robert M., primary, Laing, Naomi, primary, Tracy, Michael, primary, Freshwater, Tomoko, primary, Lee, Mark A., primary, Liu, Ji, primary, Qiu, Jingjun, primary, Rose, Shelonitda, primary, Rubin, Eric H., primary, and Moore, Kathleen, primary

Published
2023
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9. Supplementary Figure 1 from A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer

Author

Oza, Amit M., primary, Estevez-Diz, Maria, primary, Grischke, Eva-Maria, primary, Hall, Marcia, primary, Marmé, Frederik, primary, Provencher, Diane, primary, Uyar, Denise, primary, Weberpals, Johanne I., primary, Wenham, Robert M., primary, Laing, Naomi, primary, Tracy, Michael, primary, Freshwater, Tomoko, primary, Lee, Mark A., primary, Liu, Ji, primary, Qiu, Jingjun, primary, Rose, Shelonitda, primary, Rubin, Eric H., primary, and Moore, Kathleen, primary

Published
2023
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10. Supplementary Figure 2 from A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer

Author

Oza, Amit M., primary, Estevez-Diz, Maria, primary, Grischke, Eva-Maria, primary, Hall, Marcia, primary, Marmé, Frederik, primary, Provencher, Diane, primary, Uyar, Denise, primary, Weberpals, Johanne I., primary, Wenham, Robert M., primary, Laing, Naomi, primary, Tracy, Michael, primary, Freshwater, Tomoko, primary, Lee, Mark A., primary, Liu, Ji, primary, Qiu, Jingjun, primary, Rose, Shelonitda, primary, Rubin, Eric H., primary, and Moore, Kathleen, primary

Published
2023
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14. Supplementary Tables S1-S3 from Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Neutropenia during Phase I Development of Liposome-Entrapped Paclitaxel

Author

Fetterly, Gerald J., primary, Grasela, Thaddeus H., primary, Sherman, Jeffrey W., primary, Dul, Jeanne L., primary, Grahn, Amy, primary, Lecomte, Diane, primary, Fiedler-Kelly, Jill, primary, Damjanov, Nevena, primary, Fishman, Mayer, primary, Kane, Michael P., primary, Rubin, Eric H., primary, and Tan, Antoinette R., primary

Published
2023
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16. Case Studies for Overcoming Challenges in Using Big Data in Cancer

Author

Sweeney, Shawn M., primary, Hamadeh, Hisham K., additional, Abrams, Natalie, additional, Adam, Stacey J., additional, Brenner, Sara, additional, Connors, Dana E., additional, Davis, Gerard J., additional, Fiore, Louis D., additional, Gawel, Susan H., additional, Grossman, Robert L., additional, Hanlon, Sean E., additional, Hsu, Karl, additional, Kelloff, Gary J., additional, Kirsch, Ilan R., additional, Louv, Bill, additional, McGraw, Deven, additional, Meng, Frank, additional, Milgram, Daniel, additional, Miller, Robert S., additional, Morgan, Emily, additional, Mukundan, Lata, additional, O'Brien, Thomas, additional, Robbins, Paul, additional, Rubin, Eric H., additional, Rubinstein, Wendy S., additional, Salmi, Liz, additional, Schaller, Teilo H., additional, Shi, George, additional, Sigman, Caroline C., additional, and Srivastava, Sudhir, additional

Published
2023
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17. Challenges to Using Big Data in Cancer

Author

Sweeney, Shawn M., primary, Hamadeh, Hisham K., additional, Abrams, Natalie, additional, Adam, Stacey J., additional, Brenner, Sara, additional, Connors, Dana E., additional, Davis, Gerard J., additional, Fiore, Louis, additional, Gawel, Susan H., additional, Grossman, Robert L., additional, Hanlon, Sean E., additional, Hsu, Karl, additional, Kelloff, Gary J., additional, Kirsch, Ilan R., additional, Louv, Bill, additional, McGraw, Deven, additional, Meng, Frank, additional, Milgram, Daniel, additional, Miller, Robert S., additional, Morgan, Emily, additional, Mukundan, Lata, additional, O'Brien, Thomas, additional, Robbins, Paul, additional, Rubin, Eric H., additional, Rubinstein, Wendy S., additional, Salmi, Liz, additional, Schaller, Teilo, additional, Shi, George, additional, Sigman, Caroline C., additional, and Srivastava, Sudhir, additional

Published
2023
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24. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors

Author

Cristescu, Razvan, Aurora-Garg, Deepti, Albright, Andrew, Xu, Lei, Liu, Xiao Qiao, Loboda, Andrey, Lang, Lixin, Jin, Fan, Rubin, Eric H, Snyder, Alexandra, and Lunceford, Jared

Subjects
Male, Cancer Research, Immunology, Antibodies, Monoclonal, Humanized, programmed cell death 1 receptor, B7-H1 Antigen, Neoplasms, Immunotherapy Biomarkers, Exome Sequencing, Biomarkers, Tumor, Humans, Immunology and Allergy, Immune Checkpoint Inhibitors, RC254-282, Aged, Retrospective Studies, Pharmacology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Treatment Outcome, Oncology, tumor biomarkers, Mutation, Molecular Medicine, Female, Microsatellite Instability, immunotherapy
Abstract

BackgroundSeveral studies have evaluated the relationship between tumor mutational burden (TMB) and outcomes of immune checkpoint inhibitors. In the phase II KEYNOTE-158 study of pembrolizumab monotherapy for previously treated recurrent or metastatic cancer, high TMB as assessed by the FoundationOne CDx was associated with an improved objective response rate (ORR).MethodsWe retrospectively assessed the relationship between TMB and efficacy in participants with previously treated advanced solid tumors enrolled in 12 trials that evaluated pembrolizumab monotherapy, including 3 randomized trials that compared pembrolizumab with chemotherapy. TMB was assessed in formalin-fixed, paraffin-embedded pretreatment tumor samples by whole-exome sequencing. High TMB was defined as ≥175 mutations/exome. Microsatellite instability (MSI) phenotype was based on whole-exome sequencing results. Programmed death ligand 1 (PD-L1) expression was assessed by immunohistochemistry. The primary end point was ORR assessed per RECIST V.1.1 by independent central review. Other end points included progression-free survival (PFS) assessed per RECIST V.1.1 by independent central review and overall survival (OS).ResultsOf the 2234 participants in the analysis, 1772 received pembrolizumab monotherapy and 462 received chemotherapy. Among the pembrolizumab-treated participants, ORR was 31.4% (95% CI 27.1 to 36.0) in the 433 participants with TMB ≥175 mutations/exome and 9.5% (95% CI 8.0 to 11.2) in the 1339 participants with TMB ConclusionsTMB ≥175 mutations/exome is associated with clinically meaningful improvement in the efficacy of pembrolizumab monotherapy and improved outcomes for pembrolizumab versus chemotherapy across a wide range of previously treated advanced solid tumor types. These data suggest TMB has broad clinical utility irrespective of tumor type, PD-L1 expression, or MSI status and support its use as a predictive biomarker for pembrolizumab monotherapy in participants with previously treated advanced solid tumors.

Published
2022

34. A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer

Author

Oza, Amit M., primary, Estevez-Diz, Maria, additional, Grischke, Eva-Maria, additional, Hall, Marcia, additional, Marmé, Frederik, additional, Provencher, Diane, additional, Uyar, Denise, additional, Weberpals, Johanne I., additional, Wenham, Robert M., additional, Laing, Naomi, additional, Tracy, Michael, additional, Freshwater, Tomoko, additional, Lee, Mark A., additional, Liu, Ji, additional, Qiu, Jingjun, additional, Rose, Shelonitda, additional, Rubin, Eric H., additional, and Moore, Kathleen, additional

Published
2020
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35. Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce

Author

Kluger, Harriet M., primary, Tawbi, Hussein A., additional, Ascierto, Maria L., additional, Bowden, Michaela, additional, Callahan, Margaret K., additional, Cha, Edward, additional, Chen, Helen X., additional, Drake, Charles G., additional, Feltquate, David M., additional, Ferris, Robert L., additional, Gulley, James L., additional, Gupta, Shilpa, additional, Humphrey, Rachel W., additional, LaVallee, Theresa M., additional, Le, Dung T., additional, Hubbard-Lucey, Vanessa M., additional, Papadimitrakopoulou, Vassiliki A., additional, Postow, Michael A., additional, Rubin, Eric H., additional, Sharon, Elad, additional, Taube, Janis M., additional, Topalian, Suzanne L., additional, Zappasodi, Roberta, additional, Sznol, Mario, additional, and Sullivan, Ryan J., additional

Published
2020
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43. Challenges with Novel Clinical Trial Designs: Master Protocols

Author

Cecchini, Michael, primary, Rubin, Eric H., additional, Blumenthal, Gideon M., additional, Ayalew, Kassa, additional, Burris, Howard A., additional, Russell-Einhorn, Michele, additional, Dillon, Hildy, additional, Lyerly, H. Kim, additional, Reaman, Gregory H., additional, Boerner, Scott, additional, and LoRusso, Patricia M., additional

Published
2019
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44. Seamless Designs: Current Practice and Considerations for Early-Phase Drug Development in Oncology

Author

Hobbs, Brian P, primary, Barata, Pedro C, additional, Kanjanapan, Yada, additional, Paller, Channing J, additional, Perlmutter, Jane, additional, Pond, Gregory R, additional, Prowell, Tatiana M, additional, Rubin, Eric H, additional, Seymour, Lesley K, additional, Wages, Nolan A, additional, Yap, Timothy A, additional, Feltquate, David, additional, Garrett-Mayer, Elizabeth, additional, Grossman, William, additional, Hong, David S, additional, Ivy, S Percy, additional, Siu, Lillian L, additional, Reeves, Steven A, additional, and Rosner, Gary L, additional

Published
2018
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47. Identification of phosphorylation sites of TOPORS and a role for serine 98 in the regulation of ubiquitin but not SUMO E3 ligase activity

Author

Hye-Jin Park, Haiyan Zhang, Kulkarni, Diptee, Kerrigan, John, Pungaliya, Pooja, Saleem, Ahamed, and Rubin, Eric H.

Subjects
Mass spectrometry -- Usage, Phosphorylation -- Analysis, Serine -- Chemical properties, Ubiquitin-proteasome system -- Analysis, Biological sciences, Chemistry
Abstract

Mass spectrometry is used for identifying the post-translational modifications of TOPORS and the role of phosphorylation of serine 98, which is adjacent to the RING domain, is examined. The results have shown that phosphorylation of serine 98 has regulated the ubiquitin but not the SUMO ligase activity of TOPORS, which is consistent with a potential binary switch function for TOPORS in protein ubiquitination versus sumoylation.

Published
2008

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