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Article ; Online: Next-Generation Approaches to Immuno-Oncology in GI Cancers.

Hecht, J Randolph / Mitchell, Jasmine / Morelli, Maria Pia / Anandappa, Gayathri / Yang, James C

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2023 Volume 43, Page(s) e389072

Abstract: Immunotherapy has only had a modest impact on the treatment of advanced GI malignancies. Microsatellite-stable colorectal cancer and pancreatic adenocarcinoma, the most common GI tumors, have not benefited from treatment with standard immune checkpoint ... ...

Abstract	Immunotherapy has only had a modest impact on the treatment of advanced GI malignancies. Microsatellite-stable colorectal cancer and pancreatic adenocarcinoma, the most common GI tumors, have not benefited from treatment with standard immune checkpoint inhibitors. With this huge unmet need, multiple approaches are being tried to overcome barriers to better anticancer outcomes. This article reviews a number of novel approaches to immunotherapy for these tumors. These include the use of novel checkpoint inhibitors such as a modified anti-cytotoxic T lymphocyte-associated antigen-4 antibody and antibodies to lymphocyte-activation gene 3, T cell immunoreceptor with immunoglobulin and ITIM domains, T-cell immunoglobulin-3, CD47, and combinations with signal transduction inhibitors. We will discuss other trials that aim to elicit an antitumor T-cell response using cancer vaccines and oncolytic viruses. Finally, we review attempts to replicate in GI cancers the frequent and durable responses seen in hematologic malignancies with immune cell therapies.
MeSH term(s)	Humans ; Adenocarcinoma ; Pancreatic Neoplasms/drug therapy ; Gastrointestinal Neoplasms/drug therapy ; Antineoplastic Agents/therapeutic use ; T-Lymphocytes ; Immunotherapy
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2431126-1
ISSN	1548-8756 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1548-8748
DOI	10.1200/EDBK_389072
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Article ; Online: Familial Duodenal Somatostatinomatosis Not Associated With a Known Genetic Syndrome.

Yu, Run / Rao, Jianyu / Zhai, Jing / Hecht, J Randolph / Pisegna, Joseph R

Pancreas

2022 Volume 51, Issue 8, Page(s) 1056–1060

Abstract: Abstract: We report a father and his daughter who both had multiple somatostatinomas in the duodenal bulb without a known syndrome. The father, at age 68 years, was incidentally found to harbor 4 approximately 1.5-cm well-differentiated neuroendocrine ... ...

Abstract	Abstract: We report a father and his daughter who both had multiple somatostatinomas in the duodenal bulb without a known syndrome. The father, at age 68 years, was incidentally found to harbor 4 approximately 1.5-cm well-differentiated neuroendocrine tumors in the duodenal bulb. His preoperative somatostatin level was elevated. He underwent partial duodenectomy and regional lymph node dissection; one lymph node was positive for metastasis. One year postoperatively, a recurrence was found in the surgical bed; he was treated with octreotide for 2 years, which stabilized the recurrent tumor. Ten years postoperatively, the mucosa of his remaining duodenum was normal. His daughter, at age 53 years, was found to harbor multiple small neuroendocrine tumors in the duodenal bulb. Immunostaining of available specimens showed that the neuroendocrine tumors from the father and daughter both were strongly positive for somatostatin. Micronodules of somatostatin-expressing neuroendocrine cells were found in the parts of the specimens uninvolved with the tumors. Both patients exhibited no evidence of known syndromes associated with somatostatinoma. The daughter did not harbor mutations in 93 genes commonly found in genetic tumor syndromes. The 2 cases thus suggest a novel, autosomal dominant, genetic syndrome of familial duodenal somatostatinomatosis.
MeSH term(s)	Male ; Humans ; Aged ; Middle Aged ; Duodenal Neoplasms/genetics ; Duodenal Neoplasms/complications ; Neoplasm Recurrence, Local ; Duodenum/pathology ; Somatostatinoma/diagnosis ; Somatostatinoma/genetics ; Somatostatinoma/complications ; Neuroendocrine Tumors/pathology ; Somatostatin/therapeutic use ; Pancreatic Neoplasms/pathology
Chemical Substances	Somatostatin (51110-01-1)
Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	632831-3
ISSN	1536-4828 ; 0885-3177
ISSN (online)	1536-4828
ISSN	0885-3177
DOI	10.1097/MPA.0000000000002126
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Article ; Online: Fecal and Tissue Microbiota Are Associated with Tumor T-Cell Infiltration and Mesenteric Lymph Node Involvement in Colorectal Cancer.

Luu, Kayti / Ye, Jason Y / Lagishetty, Venu / Liang, Fengting / Hauer, Megan / Sedighian, Farzaneh / Kwaan, Mary R / Kazanjian, Kevork K / Hecht, J Randolph / Lin, Anne Y / Jacobs, Jonathan P

Nutrients

2023 Volume 15, Issue 2

Abstract: Colorectal cancer (CRC) is associated with alterations of the fecal and tissue-associated microbiome. Preclinical models support a pathogenic role of the microbiome in CRC, including in promoting metastasis and modulating antitumor immune responses. To ... ...

Abstract	Colorectal cancer (CRC) is associated with alterations of the fecal and tissue-associated microbiome. Preclinical models support a pathogenic role of the microbiome in CRC, including in promoting metastasis and modulating antitumor immune responses. To investigate whether the microbiome is associated with lymph node metastasis and T cell infiltration in human CRC, we performed 16S rRNA gene sequencing of feces, tumor core, tumor surface, and healthy adjacent tissue collected from 34 CRC patients undergoing surgery (28 fecal samples and 39 tissue samples). Tissue microbiome profiles-including increased
MeSH term(s)	Humans ; Colorectal Neoplasms/pathology ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Lymph Nodes ; Microbiota ; RNA, Ribosomal, 16S/genetics ; Lymphocytes, Tumor-Infiltrating ; T-Lymphocytes/immunology
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15020316
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Article: VISUAL VIGNETTE.

Yu, Run / Quon, Andrew / Hecht, J Randolph

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

2017 Volume 23, Issue 10, Page(s) 1276

MeSH term(s)	Aged ; Carcinoid Tumor/diagnostic imaging ; Colonoscopy ; Humans ; Ileal Neoplasms/diagnostic imaging ; Male
Language	English
Publishing date	2017-03-23
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1473503-9
ISSN	1530-891X
ISSN	1530-891X
DOI	10.4158/EP171809.VV
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Zs.A 5034: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Current and emerging therapies for metastatic colorectal cancer: applying research findings to clinical practice.

Hecht, J Randolph

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists

2008 Volume 65, Issue 11 Suppl 4, Page(s) S15–21; quiz S22–4

Abstract: Purpose: The results of clinical trials that led to modern first- and second-line chemotherapeutic regimens for metastatic colorectal cancer, including studies of recently introduced monoclonal antibody products that target vascular endothelial growth ... ...

Abstract	Purpose: The results of clinical trials that led to modern first- and second-line chemotherapeutic regimens for metastatic colorectal cancer, including studies of recently introduced monoclonal antibody products that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), are described, as well as new therapeutic targets being studied and challenges in research to identify and evaluate new therapies. Summary: Modern chemotherapy regimens for first-line treatment of metastatic colorectal cancer contain fluorouracil, leucovorin, either oxaliplatin or irinotecan, and the VEGF inhibitor bevacizumab. The EGFR inhibitors cetuximab and panitumumab currently are reserved for second- or third-line therapy, but their role could change as the results of clinical research become available. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin pathway, src kinases, and insulin-like growth factor-1 receptor are among the targets of current research. Identifying the subset of patients with metastatic colorectal cancer who stand to benefit from a particular therapy presents a challenge in conducting clinical research. Conclusion: Modern chemotherapeutic and monoclonal antibody regimens have improved survival in patients with meta-static colorectal cancer. The optimal combinations, timing, and sequence of agents remain to be determined.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Antineoplastic Protocols ; Bevacizumab ; Camptothecin/analogs & derivatives ; Camptothecin/therapeutic use ; Clinical Trials as Topic ; Colorectal Neoplasms/drug therapy ; ErbB Receptors/drug effects ; Humans ; Irinotecan ; Neoplasm Metastasis/drug therapy ; Organoplatinum Compounds/therapeutic use ; Oxaliplatin
Chemical Substances	Angiogenesis Inhibitors ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Organoplatinum Compounds ; Oxaliplatin (04ZR38536J) ; Bevacizumab (2S9ZZM9Q9V) ; Irinotecan (7673326042) ; ErbB Receptors (EC 2.7.10.1) ; Camptothecin (XT3Z54Z28A)
Language	English
Publishing date	2008-05-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1224627-x
ISSN	1535-2900 ; 1079-2082
ISSN (online)	1535-2900
ISSN	1079-2082
DOI	10.2146/ajhp080102
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Zs.A 419: Show issues

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Article: Successful gastrointestinal cancer drug development.

Hecht, J Randolph

Seminars in oncology

2006 Volume 33, Issue 6 Suppl 11, Page(s) S24–7

Abstract: A large number of new drugs have been approved over the past 10 years for the treatment of both common and rare gastrointestinal malignancies. Many other agents, however, have failed at a great cost of financial and patient resources. Drug development ... ...

Abstract	A large number of new drugs have been approved over the past 10 years for the treatment of both common and rare gastrointestinal malignancies. Many other agents, however, have failed at a great cost of financial and patient resources. Drug development must identify potentially active compounds and reveal the most effective and least toxic manner and population in which to administer compounds. Pharmaceutical companies must show therapeutic efficacy and achieve regulatory approval as well as success in the marketplace to recoup their investment. It is worth examining successful examples of drug development such as imatinib, delayed but eventually successful agents such as oxaliplatin, as well as failures such as SU-5416, and applying those lessons to current and future drug development.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Chemistry, Pharmaceutical ; Clinical Trials as Topic ; Drug Design ; Drug Evaluation ; Gastrointestinal Neoplasms/drug therapy ; Humans
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2006-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	189220-4
ISSN	1532-8708 ; 0093-7754
ISSN (online)	1532-8708
ISSN	0093-7754
DOI	10.1053/j.seminoncol.2006.10.001
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Zs.A 1348: Show issues

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Article ; Online: Preclinical and Clinical Trial Results Using Talazoparib and Low-Dose Chemotherapy.

Wainberg, Zev A / Singh, Arun S / Konecny, Gottfried E / McCann, Kelly E / Hecht, J Randolph / Goldman, Jonathan / Chmielowski, Bartosz / Finn, Richard S / O'Brien, Neil / Von Euw, Erika / Price, Megan M / Martinez, Diego / Yonemoto, Lisa / Brennan, Meghan / Glaspy, John A / Slamon, Dennis J

Clinical cancer research : an official journal of the American Association for Cancer Research

2022 Volume 29, Issue 1, Page(s) 40–49

Abstract: Purpose: On the basis of preclinical data, we hypothesized that low doses of chemotherapy (10% of therapeutic doses) with full dose of a PARP inhibitor could have improved efficacy and tolerability.: Patients and methods: In this phase I dose- ... ...

Abstract	Purpose: On the basis of preclinical data, we hypothesized that low doses of chemotherapy (10% of therapeutic doses) with full dose of a PARP inhibitor could have improved efficacy and tolerability. Patients and methods: In this phase I dose-escalation study, patients with BRCA-normal advanced malignancies were assigned to either talazoparib/temozolomide or talazoparib/irinotecan. Talazoparib was dose-escalated from 500 mcg to 1 mg daily before dose escalation of temozolomide/irinotecan. The starting dose of temozolomide was 25 mg/m2/day orally on days 1 to 5 and irinotecan was 25 mg/m2/day intravenously on days 1 and 15. The primary objectives of this trial were safety and tolerability, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD). Results: Of 40 patients enrolled, 18 (mean: 7 prior therapies) were enrolled in talazoparib + temozolomide and 22 in talazoparib + irinotecan. DLTs were hematologic in both arms, but all hematologic adverse events resolved with either treatment interruption and/or dose reductions of talazoparib. The MTDs were talazoparib 1 mg + temozolomide 37.5 mg/m2 and talazoparib 1 mg + irinotecan 37.5 mg/m2. There were four partial responses in the talazoparib + temozolomide arm and five in the talazoparib + irinotecan arm for a response rate of 23% (9/40). The pharmacokinetic profiles of talazoparib + temozolomide/irinotecan were similar to that of talazoparib monotherapy. Responses were seen independent of homologous recombination (HR) status and HR deficiency score. Conclusions: These results show that talazoparib with low-dose temozolomide or irinotecan is reasonably well tolerated and demonstrates clinical activity in a wide range of cancers. Randomized trials of talazoparib with or without low-dose chemotherapy are ongoing in small cell lung cancer and ovarian cancer.
MeSH term(s)	Female ; Humans ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Irinotecan/administration & dosage ; Neoplasms/drug therapy ; Temozolomide/administration & dosage
Chemical Substances	Irinotecan (7673326042) ; talazoparib (9QHX048FRV) ; Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2022-09-22
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-22-1553
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Zs.A 4223: Show issues

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Article ; Online: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Simtuzumab in Combination with FOLFIRI for the Second-Line Treatment of Metastatic

Hecht, J Randolph / Benson, Al B / Vyushkov, Dmitry / Yang, Yingsi / Bendell, Johanna / Verma, Udit

The oncologist

2017 Volume 22, Issue 3, Page(s) 243–e23

Abstract: Lessons learned: The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group.The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in ... ...

Abstract	Lessons learned: The safety profile in the patient groups who received FOLFIRI and simtuzumab did not differ from that in the FOLFIRI and placebo group.The addition of simtuzumab to chemotherapy with FOLFIRI does not improve clinical outcomes in patients with metastatic Background: Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro. Methods: Patients with metastatic Kirsten rat sarcoma viral oncogene homolog ( Results: In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg ( Conclusion: The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Adult ; Aged ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Camptothecin/administration & dosage ; Camptothecin/analogs & derivatives ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Double-Blind Method ; Female ; Fluorouracil/administration & dosage ; Humans ; Kaplan-Meier Estimate ; Leucovorin/administration & dosage ; Male ; Middle Aged ; Proto-Oncogene Proteins p21(ras)/genetics ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; KRAS protein, human ; simtuzumab (11Z5AIU653) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT) ; Camptothecin (XT3Z54Z28A)
Language	English
Publishing date	2017-02-28
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1634/theoncologist.2016-0479
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Evaluation of Intratumoral Response Heterogeneity in Metastatic Colorectal Cancer and Its Impact on Patient Overall Survival: Findings from 10,551 Patients in the ARCAD Database.

Ou, Fang-Shu / Ahn, Daniel H / Dixon, Jesse G / Grothey, Axel / Lou, Yiyue / Kasi, Pashtoon M / Hubbard, Joleen M / Van Cutsem, Eric / Saltz, Leonard B / Schmoll, Hans-Joachim / Goldberg, Richard M / Venook, Alan P / Hoff, Paulo / Douillard, Jean-Yves / Hecht, J Randolph / Hurwitz, Herbert / Punt, Cornelis J A / Koopman, Miriam / Bokemeyer, Carsten /

Fuchs, Charles S / Diaz-Rubio, Eduardo / Tebbutt, Niall C / Cremolini, Chiara / Kabbinavar, Fairooz F / Bekaii-Saab, Tanios / Chibaudel, Benoist / Yoshino, Takayuki / Zalcberg, John / Adams, Richard A / de Gramont, Aimery / Shi, Qian

Cancers

2023 Volume 15, Issue 16

Abstract: Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into ... ...

Abstract	Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS). Patients and methods: Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic. Results: Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), Conclusion: Varied responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes.
Language	English
Publishing date	2023-08-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15164117
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Article ; Online: A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results.

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 / Jooss, Karin

Nature medicine

2024

Abstract: Therapeutic vaccines that elicit cytotoxic T cell responses targeting tumor-specific neoantigens hold promise for providing long-term clinical benefit to patients with cancer. Here we evaluated safety and tolerability of a therapeutic vaccine encoding 20 ...

Abstract	Therapeutic vaccines that elicit cytotoxic T cell responses targeting tumor-specific neoantigens hold promise for providing long-term clinical benefit to patients with cancer. Here we evaluated safety and tolerability of a therapeutic vaccine encoding 20 shared neoantigens derived from selected common oncogenic driver mutations as primary endpoints in an ongoing phase 1/2 study in patients with advanced/metastatic solid tumors. Secondary endpoints included immunogenicity, overall response rate, progression-free survival and overall survival. Eligible patients were selected if their tumors expressed one of the human leukocyte antigen-matched tumor mutations included in the vaccine, with the majority of patients (18/19) harboring a mutation in KRAS. The vaccine regimen, consisting of a chimp adenovirus (ChAd68) and self-amplifying mRNA (samRNA) in combination with the immune checkpoint inhibitors ipilimumab and nivolumab, was shown to be well tolerated, with observed treatment-related adverse events consistent with acute inflammation expected with viral vector-based vaccines and immune checkpoint blockade, the majority grade 1/2. Two patients experienced grade 3/4 serious treatment-related adverse events that were also dose-limiting toxicities. The overall response rate was 0%, and median progression-free survival and overall survival were 1.9 months and 7.9 months, respectively. T cell responses were biased toward human leukocyte antigen-matched TP53 neoantigens encoded in the vaccine relative to KRAS neoantigens expressed by the patients' tumors, indicating a previously unknown hierarchy of neoantigen immunodominance that may impact the therapeutic efficacy of multiepitope shared neoantigen vaccines. These data led to the development of an optimized vaccine exclusively targeting KRAS-derived neoantigens that is being evaluated in a subset of patients in phase 2 of the clinical study. ClinicalTrials.gov registration: NCT03953235 .
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-024-02851-9
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