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Article ; Online: For Ethical Fundraising from Patients, Respect them as Partners.

Curti, Brendan D

2022 Volume 12, Issue 1, Page(s) 9–10

MeSH term(s)	Fund Raising/methods ; Humans ; Morals ; Respect
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2632728-4
ISSN	2157-1740 ; 2157-1732
ISSN (online)	2157-1740
ISSN	2157-1732
DOI	10.1353/nib.2022.0004
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Article ; Online: Immunotherapy in Advanced Renal Cancer - Is Cure Possible?

Curti, Brendan D

The New England journal of medicine

2018 Volume 378, Issue 14, Page(s) 1344–1345

MeSH term(s)	Carcinoma, Renal Cell ; Humans ; Immunotherapy ; Kidney Neoplasms
Language	English
Publishing date	2018--05
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe1801682
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Article ; Online: Recent Advances in the Treatment of Melanoma.

Curti, Brendan D / Faries, Mark B

The New England journal of medicine

2021 Volume 384, Issue 23, Page(s) 2229–2240

MeSH term(s)	Antineoplastic Agents/therapeutic use ; Cancer Vaccines ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Margins of Excision ; Melanoma/drug therapy ; Melanoma/mortality ; Melanoma/surgery ; Neoadjuvant Therapy ; Skin Neoplasms/drug therapy ; Skin Neoplasms/mortality ; Skin Neoplasms/surgery
Chemical Substances	Antineoplastic Agents ; Cancer Vaccines ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2021-06-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMra2034861
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Article ; Online: Rapid evolution of combination therapy in melanoma.

Curti, Brendan D

The New England journal of medicine

2014 Volume 371, Issue 20, Page(s) 1929–1930

MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Azetidines/administration & dosage ; Female ; Humans ; Imidazoles/administration & dosage ; Indoles/administration & dosage ; MAP Kinase Kinase 1/antagonists & inhibitors ; Male ; Melanoma/drug therapy ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors ; Oximes/administration & dosage ; Piperidines/administration & dosage ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Pyridones/administration & dosage ; Pyrimidinones/administration & dosage ; Sulfonamides/administration & dosage
Chemical Substances	Azetidines ; GDC-0973 ; Imidazoles ; Indoles ; Oximes ; Piperidines ; Pyridones ; Pyrimidinones ; Sulfonamides ; vemurafenib (207SMY3FQT) ; trametinib (33E86K87QN) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; MAP Kinase Kinase 1 (EC 2.7.12.2) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; dabrafenib (QGP4HA4G1B)
Language	English
Publishing date	2014-11-13
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe1411158
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Article ; Online: Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition.

Siefker-Radtke, Arlene / Curti, Brendan

Nature reviews. Urology

2017 Volume 15, Issue 2, Page(s) 112–124

Abstract: Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the ... ...

Abstract	Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the immunogenic potential of metastatic urothelial carcinoma have led to the accelerated FDA approval of the immune checkpoint inhibitors atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary findings suggest additional benefits of combinations of immunotherapeutic agents as a future treatment approach in metastatic urothelial carcinoma. Treatment experience with immunotherapy suggests that these drugs are associated with a unique spectrum of immune-related adverse events and specific immune-related patterns of response, including cases of pseudoprogression, which could impede the optimal use of immune checkpoint inhibitors in the clinic. Appropriate management of immune-related adverse events and a greater awareness of immune-mediated response patterns will help to inform treatment decisions and improve patient outcomes; predictive biomarkers of response might facilitate selection of patients who are most likely to respond to and benefit from these exciting new treatments.
MeSH term(s)	Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal, Humanized/pharmacology ; Antineoplastic Agents, Immunological/pharmacology ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/metabolism ; Biomarkers, Tumor/metabolism ; CTLA-4 Antigen/antagonists & inhibitors ; Carcinoma, Transitional Cell/diagnostic imaging ; Carcinoma, Transitional Cell/drug therapy ; Clinical Trials as Topic ; Humans ; Ipilimumab/pharmacology ; Nivolumab/pharmacology ; Positron-Emission Tomography ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Urinary Bladder Neoplasms/diagnostic imaging ; Urinary Bladder Neoplasms/drug therapy
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents, Immunological ; B7-H1 Antigen ; Biomarkers, Tumor ; CD274 protein, human ; CTLA-4 Antigen ; CTLA4 protein, human ; Ipilimumab ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; durvalumab (28X28X9OKV) ; Nivolumab (31YO63LBSN) ; atezolizumab (52CMI0WC3Y) ; pembrolizumab (DPT0O3T46P) ; avelumab (KXG2PJ551I)
Language	English
Publishing date	2017-12-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2493737-X
ISSN	1759-4820 ; 1759-4812
ISSN (online)	1759-4820
ISSN	1759-4812
DOI	10.1038/nrurol.2017.190
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Article ; Online: Cancer's Dark Matter: Lighting the Abyss Unveils Universe of New Therapies.

Fox, Bernard A / Urba, Walter J / Jensen, Shawn M / Page, David B / Curti, Brendan D / Sanborn, Rachel E / Leidner, Rom S

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

2023 Volume 29, Issue 12, Page(s) 2173–2175

Abstract: The authors of a recent study identified noncanonical peptides (NCP) presented by cancer cells' HLA and observed lack of reactivity to these antigens by endogenous tumor-reactive T cells. In vitro sensitization generated NCP-reactive T cells that ... ...

Abstract	The authors of a recent study identified noncanonical peptides (NCP) presented by cancer cells' HLA and observed lack of reactivity to these antigens by endogenous tumor-reactive T cells. In vitro sensitization generated NCP-reactive T cells that recognized epitopes shared by a majority of cancers tested, providing opportunities for novel therapies to shared antigens. See related article by Lozano-Rabella et al., p. 2250.
MeSH term(s)	Humans ; Antigens, Neoplasm/immunology ; Melanoma/immunology ; Ligands ; Lighting ; Proteogenomics ; Peptides
Chemical Substances	Antigens, Neoplasm ; Ligands ; Peptides
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-0422
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Zs.A 4223: Show issues

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Article ; Online: Clinical deployment of antibodies for treatment of melanoma.

Curti, Brendan D / Urba, Walter J

Molecular immunology

2015 Volume 67, Issue 2 Pt A, Page(s) 18–27

Abstract: The concept of using immunotherapy to treat melanoma has existed for decades. The rationale comes from the knowledge that many patients with melanoma have endogenous immune responses against their tumor cells and clinically meaningful tumor regression ... ...

Abstract	The concept of using immunotherapy to treat melanoma has existed for decades. The rationale comes from the knowledge that many patients with melanoma have endogenous immune responses against their tumor cells and clinically meaningful tumor regression can be achieved in a minority of patients using cytokines such as interleukin-2 and adoptive cellular therapy. In the last 5 years there has been a revolution in the clinical management of melanoma in large measure based on the development of antibodies that influence T cell regulatory pathways by overcoming checkpoint inhibition and providing co-stimulation, either of which results in significantly more effective immune-mediated tumor destruction. This review will describe the pre-clinical and clinical application of antagonistic antibodies targeting the T-cell checkpoints cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), and agonistic antibodies targeting the costimulatory pathways OX40 and 4-1BB. Recent progress and opportunities for future investigation of combination antibody therapy will be described.
MeSH term(s)	Antibodies/immunology ; Antibodies/therapeutic use ; CTLA-4 Antigen/antagonists & inhibitors ; CTLA-4 Antigen/immunology ; CTLA-4 Antigen/metabolism ; Humans ; Immunotherapy/methods ; Immunotherapy/trends ; Melanoma/immunology ; Melanoma/metabolism ; Melanoma/therapy ; Models, Immunological ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/immunology ; Programmed Cell Death 1 Receptor/metabolism ; Receptors, OX40/agonists ; Receptors, OX40/immunology ; Receptors, OX40/metabolism ; Treatment Outcome ; Tumor Necrosis Factor Receptor Superfamily, Member 9/agonists ; Tumor Necrosis Factor Receptor Superfamily, Member 9/immunology ; Tumor Necrosis Factor Receptor Superfamily, Member 9/metabolism
Chemical Substances	Antibodies ; CTLA-4 Antigen ; Programmed Cell Death 1 Receptor ; Receptors, OX40 ; TNFRSF4 protein, human ; Tumor Necrosis Factor Receptor Superfamily, Member 9
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2015.01.025
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Zs.A 166: Show issues

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Article ; Online: A Phase II, Single-arm Trial of Sunitinib and Erlotinib in Advanced Renal Cell Carcinoma.

Feng, Zizhen / Curti, Brendan D / Quinn, David I / Strother, John M / Chen, Zunqiu / Agnor, Rebecca / Beer, Tomasz M / Ryan, Christopher W

Clinical genitourinary cancer

2022 Volume 20, Issue 5, Page(s) 415–422

Abstract: Background: Overexpression of the epidermal growth factor receptor (EGFR) and its ligands occur frequently in renal cell carcinoma (RCC). Combined vascular endothelial growth factor receptor (VEGF-R) and EGFR inhibition may overcome resistance to VEGF-R ...

Abstract	Background: Overexpression of the epidermal growth factor receptor (EGFR) and its ligands occur frequently in renal cell carcinoma (RCC). Combined vascular endothelial growth factor receptor (VEGF-R) and EGFR inhibition may overcome resistance to VEGF-R inhibitor monotherapy. We performed a dose-escalation phase II study of sunitinib plus erlotinib in advanced renal cell carcinoma. Patients and methods: Patients with metastatic clear cell or papillary RCC were eligible. Prior therapy was allowed except sunitinib or erlotinib. Three dose levels of erlotinib (50, 100, 150 mg daily) were evaluated in combination with sunitinib 50 mg. Thirty-seven patients were treated at maximum tolerated dose to determine efficacy. The primary endpoint was 8-month progression-free survival (PFS) rate. The trial was powered to assess for a difference between a median PFS of less than 50% with a targeted 70% PFS for the combination. Results: The 8-month PFS rate was 40% (95% CI: 23-56). Median PFS was 5.8 months (95% CI: 4.1-9.7) and median overall survival (OS) was 26.3 months (95% CI: 16.1-34.0). The objective response rate was 22% and an additional 59% of patients had stable disease for at least 6 weeks. The most common adverse events for all grades were diarrhea, rash, fatigue, and dysgeusia. Dose reduction in 1 or both of the drugs was undertaken in 17 (46%) patients, while 5 (14%) discontinued study therapy due to toxicity. Conclusion: While sunitinib and erlotinib are combinable,the 8-month PFS rate did not suggest efficacy improvement over sunitinib monotherapy (NCT00425386).
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Carcinoma, Renal Cell/pathology ; Disease-Free Survival ; ErbB Receptors ; Erlotinib Hydrochloride/adverse effects ; Humans ; Kidney Neoplasms/pathology ; Receptors, Vascular Endothelial Growth Factor ; Sunitinib/therapeutic use ; Vascular Endothelial Growth Factor A
Chemical Substances	Vascular Endothelial Growth Factor A ; Erlotinib Hydrochloride (DA87705X9K) ; ErbB Receptors (EC 2.7.10.1) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1) ; Sunitinib (V99T50803M)
Language	English
Publishing date	2022-05-05
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2225121-2
ISSN	1938-0682 ; 1558-7673
ISSN (online)	1938-0682
ISSN	1558-7673
DOI	10.1016/j.clgc.2022.04.018
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Article ; Online: A phase 1 study of triple-targeted therapy with BRAF, MEK, and AKT inhibitors for patients with BRAF-mutated cancers.

Algazi, Alain P / Moon, James / Lao, Christopher D / Chmielowski, Bartosz / Kendra, Kari L / Lewis, Karl D / Gonzalez, Rene / Kim, Kevin / Godwin, John E / Curti, Brendan D / Latkovic-Taber, Michaella / Lomeli, Shirley H / Gufford, Brandon T / Scumpia, Philip O / Lo, Roger S / Othus, Megan / Ribas, Antoni

Cancer

2024 Volume 130, Issue 10, Page(s) 1784–1796

Abstract: Background: Aberrant PI3K/AKT signaling in BRAF-mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF-mutated solid tumors (ClinicalTrials.gov identifier ... ...

Abstract	Background: Aberrant PI3K/AKT signaling in BRAF-mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF-mutated solid tumors (ClinicalTrials.gov identifier NCT01902173). Methods: Patients with BRAF V600E/V600K-mutant solid tumors received oral dabrafenib at 150 mg twice daily with dose escalation of oral uprosertib starting at 50 mg daily, or, in the triplet cohorts, with dose escalation of both oral trametinib starting at 1.5 mg daily and oral uprosertib starting at 25 mg daily. Dose-limiting toxicities (DLTs) were assessed within the first 56 days of treatment. Radiographic responses were assessed at 8-week intervals. Results: Twenty-seven patients (22 evaluable) were enrolled in parallel doublet and triplet cohorts. No DLTs were observed in the doublet cohorts (N = 7). One patient had a DLT at the maximum administered dose of triplet therapy (dabrafenib 150 mg twice daily and trametinib 2 mg daily plus uprosertib 75 mg daily). Three patients in the doublet cohorts had partial responses (including one who had BRAF inhibitor-resistant melanoma). Two patients in the triplet cohorts had a partial response, and one patient had an unconfirmed partial response. Pharmacokinetic data suggested reduced dabrafenib and dabrafenib metabolite exposure in patients who were also exposed to both trametinib and uprosertib, but not in whose who were exposed to uprosertib without trametinib. Conclusions: Concomitant inhibition of both the MAPK and PI3K-AKT pathways for the treatment of BRAF-mutated cancers was well tolerated, leading to objective responses, but higher level drug-drug interactions affected exposure to dabrafenib and its metabolites.
MeSH term(s)	Humans ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Female ; Male ; Middle Aged ; Aged ; Adult ; Pyridones/administration & dosage ; Pyridones/adverse effects ; Pyrimidinones/administration & dosage ; Pyrimidinones/adverse effects ; Pyrimidinones/therapeutic use ; Imidazoles/administration & dosage ; Imidazoles/therapeutic use ; Imidazoles/adverse effects ; Imidazoles/pharmacokinetics ; Proto-Oncogene Proteins c-akt/metabolism ; Oximes/administration & dosage ; Oximes/adverse effects ; Oximes/therapeutic use ; Neoplasms/drug therapy ; Neoplasms/genetics ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Mutation ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use ; Aged, 80 and over ; Molecular Targeted Therapy
Chemical Substances	Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; dabrafenib (QGP4HA4G1B) ; BRAF protein, human (EC 2.7.11.1) ; Pyridones ; Pyrimidinones ; Imidazoles ; trametinib (33E86K87QN) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Oximes ; Protein Kinase Inhibitors
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article ; Clinical Trial, Phase I ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35200
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Article: A phase Ib study of interleukin-2 plus pembrolizumab for patients with advanced melanoma.

Silk, Ann W / Curti, Brendan / Bryan, Jennifer / Saunders, Tracie / Shih, Weichung / Kane, Michael P / Hannon, Phoebe / Fountain, Christopher / Felcher, Jessica / Zloza, Andrew / Kaufman, Howard L / Mehnert, Janice M / McDermott, David F

Frontiers in oncology

2023 Volume 13, Page(s) 1108341

Abstract: Introduction: High-dose interleukin-2 (HD IL-2) and pembrolizumab are each approved as single agents by the U.S. F.D.A. for the treatment of metastatic melanoma. There is limited data using the agents concurrently. The objectives of this study were to ... ...

Abstract	Introduction: High-dose interleukin-2 (HD IL-2) and pembrolizumab are each approved as single agents by the U.S. F.D.A. for the treatment of metastatic melanoma. There is limited data using the agents concurrently. The objectives of this study were to characterize the safety profile of IL-2 in combination with pembrolizumab in patients with unresectable or metastatic melanoma. Methods: In this Phase Ib study, patients received pembrolizumab (200 mg IV every 3 weeks) and escalating doses of IL-2 (6,000 or 60,000 or 600,000 IU/kg IV bolus every 8 hours up to 14 doses per cycle) in cohorts of 3 patients. Prior treatment with a PD-1 blocking antibody was allowed. The primary endpoint was the maximum tolerated dose (MTD) of IL-2 when co-administered with pembrolizumab. Results: Ten participants were enrolled, and 9 participants were evaluable for safety and efficacy. The majority of the evaluable participants (8/9) had been treated with PD-1 blocking antibody prior to enrollment. Patients received a median of 42, 22, and 9 doses of IL-2 in the low, intermediate, and high dose cohorts, respectively. Adverse events were more frequent with increasing doses of IL-2. No dose limiting toxicities were observed. The MTD of IL-2 was not reached. One partial response occurred in 9 patients (11%). The responding patient, who had received treatment with an anti-PD-1 prior to study entry, was treated in the HD IL-2 cohort. Discussion: Although the sample size was small, HD IL-2 therapy in combination with pembrolizumab appears feasible and tolerable. Clinical trial registration: ClinicalTrials.gov, identifier NCT02748564.
Language	English
Publishing date	2023-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1108341
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