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2. A phase II randomized, double-blind trial of a polyvalent Vaccine-KLH conjugate (NSC 748933 IND# 14384) + OPT-821 versus OPT-821 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer who are in second or third complete remission: An NRG Oncology/GOG study

Author

O'Cearbhaill, Roisin E, Deng, Wei, Chen, Lee-May, Lucci, Joseph A, Behbakht, Kian, Spirtos, Nick M, Muller, Carolyn Y, Benigno, Benedict B, Powell, Matthew A, Berry, Emily, Tewari, Krishnansu S, Hanjani, Parviz, Lankes, Heather A, Aghajanian, Carol, and Sabbatini, Paul J

Subjects
Clinical Trials and Supportive Activities, Immunization, Cancer, Vaccine Related, Rare Diseases, Clinical Research, Prevention, Pediatric Research Initiative, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adjuvants, Immunologic, Adult, Aged, Aged, 80 and over, Cancer Vaccines, Carcinoma, Ovarian Epithelial, Double-Blind Method, Fallopian Tube Neoplasms, Female, Hemocyanins, Humans, Middle Aged, Neoplasm Staging, Ovarian Neoplasms, Peritoneal Neoplasms, Vaccines, Conjugate, Randomized, Vaccine, Ovarian, Remission, OPT-821, Oncology and Carcinogenesis, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis
Abstract

ObjectiveEarly-phase data have demonstrated induction of antibody responses to a polyvalent vaccine conjugate (Globo-H, GM2, MUC1-TN, TF) with adjuvant OPT-821. We sought to determine if this combination decreases the hazard of progression or death compared to OPT-821 alone in patients with ovarian cancer in second/third clinical complete remission following chemotherapy. Secondary and translational objectives were overall survival (OS), safety, and immunogenicity.MethodsFrom 2010-2013, patients were randomized (1:1) to receive OPT-821±vaccine-KLH conjugate subcutaneously at weeks 1, 2, 3, 7, 11, and then every 12 weeks (total 11). Dose delay or reduction was not permitted. Patients were removed for pre-defined dose-limiting toxicity.ResultsOf 171 patients randomized, 170 were treated. Most had disease of serous histology (85%), stage 3 disease at diagnosis (77%), and had received 2 prior regimens (68%). 32% received >6 treatment cycles [median 6, each arm (p = 0.33)]. 77% discontinued due to progression, 4% due to toxicity, and 1 due to myeloid dysplastic syndrome (MDS). Maximum toxicities included grade 4 MDS and depression/personality change (1 each, unlikely related), as well as grade 3 gastrointestinal disorders and others (n = 21, 4 related). Lesser adverse events were injection site reactions (82%) and fever (11%). Estimated HR for progression-free survival (PFS) of the vaccine + OPT-821 to OPT-821 arm was 0.98 (95% CI: 0.71-1.36). At a median follow-up of 60 months, median OS was 47 and 46 months, respectively.ConclusionsVaccine + OPT-821 compared to OPT-821 alone was modestly immunogenic and did not prolong PFS or OS. Multi-remission patients are a viable, well-defined population for exploring innovative consolidation and maintenance approaches.Trial registrationNCT00857545.

Published
2019

4. A phase 1 dose-escalation study of intraperitoneal cisplatin, intravenous/intraperitoneal paclitaxel, bevacizumab, and olaparib for newly diagnosed ovarian cancer

Author

Cadoo, Karen A., Grisham, Rachel N., O'Cearbhaill, Roisin E., Boucicaut, Nicole N., Henson, Melissa, Iasonos, Alexia, Zhou, Qin, Sarasohn, Debra M., Gallagher, Jacqueline, Kravetz, Sara, Zamarin, Dmitriy, Makker, Vicky, Sabbatini, Paul J., Tew, William P., Aghajanian, Carol, and Konner, Jason A.

Published
2020
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5. Figure S1 from Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer

Author

Suehnholz, Sarah P., primary, Nissan, Moriah H., primary, Zhang, Hongxin, primary, Kundra, Ritika, primary, Nandakumar, Subhiksha, primary, Lu, Calvin, primary, Carrero, Stephanie, primary, Dhaneshwar, Amanda, primary, Fernandez, Nicole, primary, Xu, Benjamin W., primary, Arcila, Maria E., primary, Zehir, Ahmet, primary, Syed, Aijazuddin, primary, Brannon, A. Rose, primary, Rudolph, Julia E., primary, Paraiso, Eder, primary, Sabbatini, Paul J., primary, Levine, Ross L., primary, Dogan, Ahmet, primary, Gao, Jianjiong, primary, Ladanyi, Marc, primary, Drilon, Alexander, primary, Berger, Michael F., primary, Solit, David B., primary, Schultz, Nikolaus, primary, and Chakravarty, Debyani, primary

Published
2024
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6. Table S3 from Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer

Author

Suehnholz, Sarah P., primary, Nissan, Moriah H., primary, Zhang, Hongxin, primary, Kundra, Ritika, primary, Nandakumar, Subhiksha, primary, Lu, Calvin, primary, Carrero, Stephanie, primary, Dhaneshwar, Amanda, primary, Fernandez, Nicole, primary, Xu, Benjamin W., primary, Arcila, Maria E., primary, Zehir, Ahmet, primary, Syed, Aijazuddin, primary, Brannon, A. Rose, primary, Rudolph, Julia E., primary, Paraiso, Eder, primary, Sabbatini, Paul J., primary, Levine, Ross L., primary, Dogan, Ahmet, primary, Gao, Jianjiong, primary, Ladanyi, Marc, primary, Drilon, Alexander, primary, Berger, Michael F., primary, Solit, David B., primary, Schultz, Nikolaus, primary, and Chakravarty, Debyani, primary

Published
2024
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7. A phase II randomized, double-blind trial of a polyvalent Vaccine-KLH conjugate (NSC 748933 IND# 14384) + OPT-821 versus OPT-821 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer who are in second or third complete remission: An NRG Oncology/GOG study

Author

O’Cearbhaill, Roisin E., Deng, Wei, Chen, Lee-may, Lucci, Joseph A., III, Behbakht, Kian, Spirtos, Nick M., Muller, Carolyn Y., Benigno, Benedict B., Powell, Matthew A., Berry, Emily, Tewari, Krishnansu S., Hanjani, Parviz, Lankes, Heather A., Aghajanian, Carol, and Sabbatini, Paul J.

Published
2019
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8. Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer

Author

Suehnholz, Sarah P., primary, Nissan, Moriah H., additional, Zhang, Hongxin, additional, Kundra, Ritika, additional, Nandakumar, Subhiksha, additional, Lu, Calvin, additional, Carrero, Stephanie, additional, Dhaneshwar, Amanda, additional, Fernandez, Nicole, additional, Xu, Benjamin W., additional, Arcila, Maria E., additional, ZEHIR, Ahmet, additional, Syed, Aijazuddin, additional, Brannon, A. Rose, additional, Rudolph, Julia E., additional, Paraiso, Eder, additional, Sabbatini, Paul J., additional, Levine, Ross L., additional, Dogan, Ahmet, additional, Gao, Jianjiong, additional, Ladanyi, Marc, additional, Drilon, Alexander, additional, Berger, Michael F., additional, Solit, David B., additional, Schultz, Nikolaus, additional, and Chakravarty, Debyani, additional

Published
2023
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9. OncoTree: A Cancer Classification System for Precision Oncology

Author

Kundra, Ritika, Zhang, Hongxin, Sheridan, Robert, Sirintrapun, Sahussapont Joseph, Wang, Avery, Ochoa, Angelica, Wilson, Manda, Gross, Benjamin, Sun, Yichao, Madupuri, Ramyasree, Satravada, Baby A., Reales, Dalicia, Vakiani, Efsevia, Al-Ahmadie, Hikmat A., Dogan, Ahmet, Arcila, Maria, Zehir, Ahmet, Maron, Steven, Berger, Michael F., Viaplana, Cristina, Janeway, Katherine, Ducar, Matthew, Sholl, Lynette, Dogan, Snjezana, Bedard, Philippe, Surrey, Lea F., Sanchez, Iker Huerga, Syed, Aijaz, Rema, Anoop Balakrishnan, Chakravarty, Debyani, Suehnholz, Sarah, Nissan, Moriah, Iyer, Gopakumar V., Murali, Rajmohan, Bouvier, Nancy, Soslow, Robert A., Hyman, David, Younes, Anas, Intlekofer, Andrew, Harding, James J., Carvajal, Richard D., Sabbatini, Paul J., Abou-Alfa, Ghassan K., Morris, Luc, Janjigian, Yelena Y., Gallagher, Meighan M., Soumerai, Tara A., Mellinghoff, Ingo K., Hakimi, Abraham A., Fury, Matthew, Huse, Jason T., Bagrodia, Aditya, Hameed, Meera, Thomas, Stacy, Gardos, Stuart, Cerami, Ethan, Mazor, Tali, Kumari, Priti, Raman, Pichai, Shivdasani, Priyanka, MacFarland, Suzanne, Newman, Scott, Waanders, Angela, Gao, Jianjiong, Solit, David, and Schultz, Nikolaus

Published
2021
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10. Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission

Author

Manning-Geist, Beryl L., primary, Gnjatic, Sacha, additional, Aghajanian, Carol, additional, Konner, Jason, additional, Kim, Sarah H., additional, Sarasohn, Debra, additional, Soldan, Krysten, additional, Tew, William P., additional, Sarlis, Nicholas J., additional, Zamarin, Dmitriy, additional, Kravetz, Sara, additional, Laface, Ilaria, additional, Rasalan-Ho, Teresa, additional, Qi, Jingjing, additional, Wong, Phillip, additional, Sabbatini, Paul J., additional, and O’Cearbhaill, Roisin E., additional

Published
2023
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11. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients

Author

Zehir, Ahmet, Benayed, Ryma, Shah, Ronak H, Syed, Aijazuddin, Middha, Sumit, Kim, Hyunjae R, Srinivasan, Preethi, Gao, Jianjiong, Chakravarty, Debyani, Devlin, Sean M, Hellmann, Matthew D, Barron, David A, Schram, Alison M, Hameed, Meera, Dogan, Snjezana, Ross, Dara S, Hechtman, Jaclyn F, DeLair, Deborah F, Yao, JinJuan, Mandelker, Diana L, Cheng, Donavan T, Chandramohan, Raghu, Mohanty, Abhinita S, Ptashkin, Ryan N, Jayakumaran, Gowtham, Prasad, Meera, Syed, Mustafa H, Rema, Anoop Balakrishnan, Liu, Zhen Y, Nafa, Khedoudja, Borsu, Laetitia, Sadowska, Justyna, Casanova, Jacklyn, Bacares, Ruben, Kiecka, Iwona J, Razumova, Anna, Son, Julie B, Stewart, Lisa, Baldi, Tessara, Mullaney, Kerry A, Al-Ahmadie, Hikmat, Vakiani, Efsevia, Abeshouse, Adam A, Penson, Alexander V, Jonsson, Philip, Camacho, Niedzica, Chang, Matthew T, Won, Helen H, Gross, Benjamin E, Kundra, Ritika, Heins, Zachary J, Chen, Hsiao-Wei, Phillips, Sarah, Zhang, Hongxin, Wang, Jiaojiao, Ochoa, Angelica, Wills, Jonathan, Eubank, Michael, Thomas, Stacy B, Gardos, Stuart M, Reales, Dalicia N, Galle, Jesse, Durany, Robert, Cambria, Roy, Abida, Wassim, Cercek, Andrea, Feldman, Darren R, Gounder, Mrinal M, Hakimi, A Ari, Harding, James J, Iyer, Gopa, Janjigian, Yelena Y, Jordan, Emmet J, Kelly, Ciara M, Lowery, Maeve A, Morris, Luc G T, Omuro, Antonio M, Raj, Nitya, Razavi, Pedram, Shoushtari, Alexander N, Shukla, Neerav, Soumerai, Tara E, Varghese, Anna M, Yaeger, Rona, Coleman, Jonathan, Bochner, Bernard, Riely, Gregory J, Saltz, Leonard B, Scher, Howard I, Sabbatini, Paul J, Robson, Mark E, Klimstra, David S, Taylor, Barry S, Baselga, Jose, Schultz, Nikolaus, Hyman, David M, Arcila, Maria E, Solit, David B, Ladanyi, Marc, and Berger, Michael F

Subjects
Cancer -- Genetic aspects -- Research, Gene mutation -- Research, Cancer metastasis -- Genetic aspects -- Development and progression, Biological sciences, Health
Abstract

Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations. Using these data, we identified clinically relevant somatic mutations, novel noncoding alterations, and mutational signatures that were shared by common and rare tumor types. Patients were enrolled on genomically matched clinical trials at a rate of 11%. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results are publicly accessible., Author(s): Ahmet Zehir [1]; Ryma Benayed [1]; Ronak H Shah [1]; Aijazuddin Syed [1]; Sumit Middha [1]; Hyunjae R Kim [1]; Preethi Srinivasan [1]; Jianjiong Gao [2]; Debyani Chakravarty [2]; [...]

Published
2017
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13. Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination

Author

Kahn, Ryan M., primary, Ragupathi, Govind, additional, Zhou, Qin C., additional, Iasonos, Alexia, additional, Kravetz, Sara, additional, Hensley, Martee L., additional, Konner, Jason A., additional, Makker, Vicky, additional, Tew, William P., additional, Aghajanian, Carol, additional, Sabbatini, Paul J., additional, and O’Cearbhaill, Roisin E., additional

Published
2022
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16. Phase II study of enzalutamide in androgen receptor positive, recurrent, high- and low-grade serous ovarian cancer

Author

Manning-Geist, Beryl L., primary, Gordhandas, Sushmita B., additional, Giri, Dilip D., additional, Iasonos, Alexia, additional, Zhou, Qin, additional, Girshman, Jeffrey, additional, O'Cearbhaill, Roisin E., additional, Zamarin, Dmitriy, additional, Lichtman, Stuart M., additional, Sabbatini, Paul J., additional, Tew, William P., additional, Li, Karen, additional, McDonnell, Autumn S., additional, Aviki, Emeline M., additional, Chi, Dennis S., additional, Aghajanian, Carol A., additional, and Grisham, Rachel N., additional

Published
2022
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21. Erratum: Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients

Author

Zehir, Ahmet, primary, Benayed, Ryma, additional, Shah, Ronak H, additional, Syed, Aijazuddin, additional, Middha, Sumit, additional, Kim, Hyunjae R, additional, Srinivasan, Preethi, additional, Gao, Jianjiong, additional, Chakravarty, Debyani, additional, Devlin, Sean M, additional, Hellmann, Matthew D, additional, Barron, David A, additional, Schram, Alison M, additional, Hameed, Meera, additional, Dogan, Snjezana, additional, Ross, Dara S, additional, Hechtman, Jaclyn F, additional, DeLair, Deborah F, additional, Yao, JinJuan, additional, Mandelker, Diana L, additional, Cheng, Donavan T, additional, Chandramohan, Raghu, additional, Mohanty, Abhinita S, additional, Ptashkin, Ryan N, additional, Jayakumaran, Gowtham, additional, Prasad, Meera, additional, Syed, Mustafa H, additional, Rema, Anoop Balakrishnan, additional, Liu, Zhen Y, additional, Nafa, Khedoudja, additional, Borsu, Laetitia, additional, Sadowska, Justyna, additional, Casanova, Jacklyn, additional, Bacares, Ruben, additional, Kiecka, Iwona J, additional, Razumova, Anna, additional, Son, Julie B, additional, Stewart, Lisa, additional, Baldi, Tessara, additional, Mullaney, Kerry A, additional, Al-Ahmadie, Hikmat, additional, Vakiani, Efsevia, additional, Abeshouse, Adam A, additional, Penson, Alexander V, additional, Jonsson, Philip, additional, Camacho, Niedzica, additional, Chang, Matthew T, additional, Won, Helen H, additional, Gross, Benjamin E, additional, Kundra, Ritika, additional, Heins, Zachary J, additional, Chen, Hsiao-Wei, additional, Phillips, Sarah, additional, Zhang, Hongxin, additional, Wang, Jiaojiao, additional, Ochoa, Angelica, additional, Wills, Jonathan, additional, Eubank, Michael, additional, Thomas, Stacy B, additional, Gardos, Stuart M, additional, Reales, Dalicia N, additional, Galle, Jesse, additional, Durany, Robert, additional, Cambria, Roy, additional, Abida, Wassim, additional, Cercek, Andrea, additional, Feldman, Darren R, additional, Gounder, Mrinal M, additional, Hakimi, A Ari, additional, Harding, James J, additional, Iyer, Gopa, additional, Janjigian, Yelena Y, additional, Jordan, Emmet J, additional, Kelly, Ciara M, additional, Lowery, Maeve A, additional, Morris, Luc G T, additional, Omuro, Antonio M, additional, Raj, Nitya, additional, Razavi, Pedram, additional, Shoushtari, Alexander N, additional, Shukla, Neerav, additional, Soumerai, Tara E, additional, Varghese, Anna M, additional, Yaeger, Rona, additional, Coleman, Jonathan, additional, Bochner, Bernard, additional, Riely, Gregory J, additional, Saltz, Leonard B, additional, Scher, Howard I, additional, Sabbatini, Paul J, additional, Robson, Mark E, additional, Klimstra, David S, additional, Taylor, Barry S, additional, Baselga, Jose, additional, Schultz, Nikolaus, additional, Hyman, David M, additional, Arcila, Maria E, additional, Solit, David B, additional, Ladanyi, Marc, additional, and Berger, Michael F, additional

Published
2017
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22. Impact of Prophylactic Conversion to an Extended Infusion Schedule to Prevent Hypersensitivity Reactions in Ovarian Cancer Patients during Carboplatin Retreatment

Author

O’Cearbhaill, Roisin, Zhou, Qin, Iasonos, Alexia, Hensley, Martee L., Tew, William P., Aghajanian, Carol, Spriggs, David R., Lichtman, Stuart M., and Sabbatini, Paul J.

Subjects
Adult, Aged, 80 and over, Ovarian Neoplasms, Adolescent, Antineoplastic Agents, Middle Aged, Article, Drug Administration Schedule, Carboplatin, Drug Hypersensitivity, Young Adult, Fallopian Tube Neoplasms, Humans, Female, Infusions, Intravenous, Peritoneal Neoplasms, Aged, Retrospective Studies
Abstract

Repeated exposure to carboplatin can lead to hypersensitivity reactions during retreatment with carboplatin. This may prevent its further use in platinum-sensitive ovarian cancer patients. At our institution, an increasing proportion of patients are prophylactically converted to an extended schedule of infusion after 8 cycles of carboplatin. We sought to determine whether an incrementally increasing, extended 3-hour infusion of carboplatin with appropriate premedication was associated with a lower rate of hypersensitivity reactions compared to the standard 30-minute schedule in sequentially treated patients.We performed a retrospective electronic medical record review of patients with recurrent ovarian cancer retreated with carboplatin at our institution from January 1998 to December 2008.Seven hundred and seventy-seven patients with relapsed ovarian, fallopian tube, or primary peritoneal cancer were retreated with carboplatin and met study inclusion criteria. Of these, 117 (17%) developed hypersensitivity reactions during second-line or greater carboplatin-based treatment for recurrent disease. Only 6 (3.4%) of the 174 patients who received the extended schedule developed hypersensitivity reactions (0% grade 4; 50% grade 3) compared to 111 (21%) of 533 patients in the standard schedule group (13% grade 4; 77% grade 3). The first hypersensitivity episode occurred after a median of 16 platinum (carboplatin and cisplatin) treatments in the extended group compared to 9 in the standard group. Using the Fisher exact test, there was an association with a reduced incidence of hypersensitivity reactions with the extended infusion schedule (P0.001).Our data suggest appropriate premedication and prophylactic conversion to an extended infusion during carboplatin retreatment may reduce hypersensitivity reactions.

Published
2009

23. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer

Author

Sabbatini, Paul J, Ragupathi, Govind, Hood, Chandra, Aghajanian, Carol A, Juretzka, Margrit, Iasonos, Alexia, Hensley, Martee L, Spassova, Maria K, Ouerfelli, Ouathek, Spriggs, David R, Tew, William P, Konner, Jason, Clausen, Henrik, Abu Rustum, Nadeem, Dansihefsky, Samuel J, Livingston, Philip O, Sabbatini, Paul J, Ragupathi, Govind, Hood, Chandra, Aghajanian, Carol A, Juretzka, Margrit, Iasonos, Alexia, Hensley, Martee L, Spassova, Maria K, Ouerfelli, Ouathek, Spriggs, David R, Tew, William P, Konner, Jason, Clausen, Henrik, Abu Rustum, Nadeem, Dansihefsky, Samuel J, and Livingston, Philip O

Abstract

Udgivelsesdato: 2007-Jul-15, PURPOSE: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. EXPERIMENTAL DESIGN: Eleven patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were administered at weeks 1, 2, 3, 7, and 15. Periodic blood and urine samples were obtained to monitor safety (complete blood count, comprehensive panel, amylase, thyroid-stimulating hormone, and urinalysis) and antibody production (ELISA, fluorescence-activated cell sorting, and complement-dependent cytotoxicity). RESULTS: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2 in two patients), fever, myalgia, and localized injection site reactions were most frequent. No clinically relevant hematologic abnormalities were noted. No clinical or laboratory evidence of autoimmunity was seen. Serologic responses by ELISA were largely IgM against each antigen with the exception of Tn-MUC1 where both IgM and IgG responses were induced. Antibody responses were generally undetectable before immunization. After immunization, median IgM titers were as follows: Tn-MUC1, 1:640 (IgG 1:80); Tn, 1:160; TF, 1:640; Globo-H, 1:40; and STn, 1:80. Only one response was seen against Lewis Y; two were against GM2. Eight of nine patients developed responses against at least three antigens. Antibody titers peaked at weeks 4 to 8 in all patients. Fluorescence-activated cel

Published
2007

24. A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission.

Author

O'Cearbhaill, Roisin E., Ragupathi, Govind, Jianglong Zhu, Qian Wan, Mironov, Svetlana, Guangbin Yang, Spassova, Maria K., Iasonos, Alexia, Kravetz, Sara, Ouerfelli, Ouathek, Spriggs, David R., Danishefsky, Samuel J., and Sabbatini, Paul J.

Subjects
PEPTIDES, CANCER relapse, OVARIAN tumors, ANTIGENS, DIAGNOSTIC imaging, DRUG dosage, DRUG toxicity, ENZYME-linked immunosorbent assay, IMMUNOGENETICS, RESEARCH funding, SERODIAGNOSIS, TIME, TOXICITY testing, WHITE people, PILOT projects, CANCER vaccines, DISEASE remission, DATA analysis software, KAPLAN-Meier estimator, KARNOFSKY Performance Status, PREVENTION, CANCER treatment, THERAPEUTICS
Abstract

We conducted a phase I study in ovarian cancer patients to evaluate the safety and immunogenicity of a synthetic unimolecular pentavalent carbohydrate vaccine (Globo-H, GM2, sTn, TF, and Tn) supported on a peptide backbone, conjugated to keyhole limpet haemocyanin (KLH), and mixed with immunological adjuvant QS-21. Twenty-four advanced-stage, poor-risk, first-remission ovarian cancer patients were enrolled from January 2011-Septermber 2013. Three dose levels were planned (25, 50, 100 mcg) with three cohorts of six patients each, with an additional 6-patient expansion cohort at the MTD. ELISA serologic IgM and IgG responses for each antigen was defined as positive response if antibody titers were ≽1:80 over the respective patient's pre-vaccination serum. The study would be considered positive if at least four of 12 patients treated at the MTD showed immune responses for at least three of the five antigens. Twenty-four patients (median age, 54 years [range, 36-68]) were included in the safety analysis. Histology was high-grade serous in 22 patients (92%); 18 had stage III and six stage IV disease. The vaccine was well-tolerated at all doses, with no DLTs. At the highest treated dose, IgG and/or IgM responses were recorded against ¥3 antigens in 9/12 patients (75%), ≽4 in 7/12 (58%), and 5 in 3/12 (25%). With a median follow-up of 19 months (range, 2-39), 20 patients (83%) recurred and six (25%) died. The unimolecular pentavalent vaccine construct was shown to be safe and immunogenic. Such a construct greatly simplifies regulatory requirements and manufacturing, facilitates scalability, and provides adaptability. [ABSTRACT FROM AUTHOR]

Published
2016
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25. Authors' reply to Drs. Khattak and Martin

Author

O'Cearbhaill, Roisin, primary, Li, Daneng, additional, Shi, Weiji, additional, Thaler, Howard, additional, Sabbatini, Paul J., additional, Konner, Jason, additional, Hensley, Martee L., additional, Aghajanian, Carol A., additional, Lichtman, Stuart M., additional, and Tew, William P., additional

Published
2012
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26. Early Postoperative CT as a Prognostic Biomarker in Patients With Advanced Ovarian, Tubal, and Primary Peritoneal Cancer Deemed Optimally Debulked at Primary Cytoreductive Surgery

Author

Lakhman, Yulia, primary, Akin, Oguz, additional, Sohn, Michael J., additional, Zheng, Junting, additional, Moskowitz, Chaya S., additional, Iyer, Revathy B., additional, Barakat, Richard R., additional, Sabbatini, Paul J., additional, Chi, Dennis S., additional, and Hricak, Hedvig, additional

Published
2012
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27. Phase II Study of Intraperitoneal Paclitaxel Plus Cisplatin and Intravenous Paclitaxel Plus Bevacizumab As Adjuvant Treatment of Optimal Stage II/III Epithelial Ovarian Cancer

Author

Konner, Jason A., primary, Grabon, Diana M., additional, Gerst, Scott R., additional, Iasonos, Alexia, additional, Thaler, Howard, additional, Pezzulli, Sandra D., additional, Sabbatini, Paul J., additional, Bell-McGuinn, Katherine M., additional, Tew, William P., additional, Hensley, Martee L., additional, Spriggs, David R., additional, and Aghajanian, Carol A., additional

Published
2011
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28. The prophylactic conversion to an extended infusion schedule and use of premedication to prevent hypersensitivity reactions in ovarian cancer patients during carboplatin retreatment

Author

O'Cearbhaill, Roisin, primary, Zhou, Qin, additional, Iasonos, Alexia, additional, Hensley, Martee L., additional, Tew, William P., additional, Aghajanian, Carol, additional, Spriggs, David R., additional, Lichtman, Stuart M., additional, and Sabbatini, Paul J., additional

Published
2010
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30. Exploratory analysis of serum CA-125 response to surgery and the risk of relapse in patients with FIGO stage IIIC ovarian cancer

Author

Zivanovic, Oliver, primary, Sima, Camelia S., additional, Iasonos, Alexia, additional, Bell-McGuinn, Katherine M., additional, Sabbatini, Paul J., additional, Leitao, Mario M., additional, Levine, Douglas A., additional, Gardner, Ginger J., additional, Barakat, Richard R., additional, and Chi, Dennis S., additional

Published
2009
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33. Pilot Study of a Heptavalent Vaccine-Keyhole Limpet Hemocyanin Conjugate plus QS21 in Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer

Author

Sabbatini, Paul J., primary, Ragupathi, Govind, additional, Hood, Chandra, additional, Aghajanian, Carol A., additional, Juretzka, Margrit, additional, Iasonos, Alexia, additional, Hensley, Martee L., additional, Spassova, Maria K., additional, Ouerfelli, Ouathek, additional, Spriggs, David R., additional, Tew, William P., additional, Konner, Jason, additional, Clausen, Henrik, additional, Abu Rustum, Nadeem, additional, Dansihefsky, Samuel J., additional, and Livingston, Philip O., additional

Published
2007
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34. Immunization of ovarian cancer patients with a synthetic Lewisy-protein conjugate vaccine: A phase 1 trial

Author

Sabbatini, Paul J., primary, Kudryashov, Valery, additional, Ragupathi, Govindaswami, additional, Danishefsky, Samuel J., additional, Livingston, Philip O., additional, Bornmann, William, additional, Spassova, Maria, additional, Zatorski, Andrzej, additional, Spriggs, David, additional, Aghajanian, Carol, additional, Soignet, Steven, additional, Peyton, Madeline, additional, O'Flaherty, Catherine, additional, Curtin, John, additional, and Lloyd, Kenneth O., additional

Published
2000
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35. Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer.

Author

Suehnholz SP, Nissan MH, Zhang H, Kundra R, Nandakumar S, Lu C, Carrero S, Dhaneshwar A, Fernandez N, Xu BW, Arcila ME, Zehir A, Syed A, Brannon AR, Rudolph JE, Paraiso E, Sabbatini PJ, Levine RL, Dogan A, Gao J, Ladanyi M, Drilon A, Berger MF, Solit DB, Schultz N, and Chakravarty D

Subjects
Humans, Mutation, Precision Medicine methods, Medical Oncology methods, Neoplasms therapy
Abstract

There is a continuing debate about the proportion of cancer patients that benefit from precision oncology, attributable in part to conflicting views as to which molecular alterations are clinically actionable. To quantify the expansion of clinical actionability since 2017, we annotated 47,271 solid tumors sequenced with the MSK-IMPACT clinical assay using two temporally distinct versions of the OncoKB knowledge base deployed 5 years apart. Between 2017 and 2022, we observed an increase from 8.9% to 31.6% in the fraction of tumors harboring a standard care (level 1 or 2) predictive biomarker of therapy response and an almost halving of tumors carrying nonactionable drivers (44.2% to 22.8%). In tumors with limited or no clinical actionability, TP53 (43.2%), KRAS (19.2%), and CDKN2A (12.2%) were the most frequently altered genes., Significance: Although clear progress has been made in expanding the availability of precision oncology-based treatment paradigms, our results suggest a continued unmet need for innovative therapeutic strategies, particularly for cancers with currently undruggable oncogenic drivers. See related commentary by Horak and Fröhling, p. 18. This article is featured in Selected Articles from This Issue, p. 5., (©2023 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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36. Early postoperative CT as a prognostic biomarker in patients with advanced ovarian, tubal, and primary peritoneal cancer deemed optimally debulked at primary cytoreductive surgery.

Author

Lakhman Y, Akin O, Sohn MJ, Zheng J, Moskowitz CS, Iyer RB, Barakat RR, Sabbatini PJ, Chi DS, and Hricak H

Subjects
Contrast Media, Diatrizoate, Disease Progression, Female, Humans, Iohexol, Middle Aged, Postoperative Period, Prognosis, Proportional Hazards Models, Retrospective Studies, Survival Analysis, Fallopian Tube Diseases diagnostic imaging, Fallopian Tube Diseases surgery, Neoplasm, Residual diagnostic imaging, Ovarian Neoplasms diagnostic imaging, Ovarian Neoplasms surgery, Peritoneal Neoplasms diagnostic imaging, Peritoneal Neoplasms surgery, Tomography, X-Ray Computed methods
Abstract

Objective: The purpose of this article is to determine whether early postoperative CT provides prognostic information in patients with advanced ovarian, tubal, or primary peritoneal carcinoma with optimal debulking reported at primary cytoreduction., Materials and Methods: Our study included 63 patients who underwent primary cytoreductive surgery for presumed advanced ovarian cancer, who had optimal debulking (residual disease ≤ 1 cm) reported at surgery, and who underwent CT before and 7-49 days after surgery. Two radiologists independently retrospectively interpreted all postoperative CT scans and scored lesions on a 5-point scale, where 1 indicates normal and 5 indicates definitely malignant. Lesions larger than 1 cm with a CT score of 4 or 5 were considered suboptimally debulked residual disease., Results: Suboptimally debulked residual disease on CT (range, 1.1-5.8 cm) was reported by reader 1 for 29 of 63 patients (46%) and by reader 2 for 31 of 63 patients (49%), with substantial interobserver agreement (κ = 0.75). Patients with suboptimally debulked residual disease on CT had significantly worse median progression-free survival (p = 0.001, both readers) and overall survival (p ≤ 0.010, both readers). By univariate and multivariate analyses, suboptimally debulked residual disease on CT remained a significant independent predictor of progression-free survival (p = 0.001, both readers) and overall survival (p ≤ 0.006, both readers)., Conclusion: Our study showed that residual disease larger than 1 cm was present on early postoperative CT in almost half of the patients deemed to have optimally debulked disease at primary cytoreduction. Residual disease larger than 1 cm detected on early postoperative CT was associated with significant decreases in both progression-free and overall survival.

Published
2012
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