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Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates Dec 2023

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …


Bispecific T-Cell Engagers Therapies In Solid Tumors: Focusing On Prostate Cancer, Diana C Simão, Kevin K Zarrabi, José L Mendes, Ricardo Luz, Jorge A Garcia, William Kevin Kelly, Pedro C Barata Feb 2023

Bispecific T-Cell Engagers Therapies In Solid Tumors: Focusing On Prostate Cancer, Diana C Simão, Kevin K Zarrabi, José L Mendes, Ricardo Luz, Jorge A Garcia, William Kevin Kelly, Pedro C Barata

Department of Medical Oncology Faculty Papers

Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors' immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. …


Efficacy And Safety Of Lifileucel, A One-Time Autologous Tumor-Infiltrating Lymphocyte (Til) Cell Therapy, In Patients With Advanced Melanoma After Progression On Immune Checkpoint Inhibitors And Targeted Therapies: Pooled Analysis Of Consecutive Cohorts Of The C-144-01 Study, Jason Chesney, Karl D Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q Phan, John M Kirkwood, Jessica C Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J S Furness, Nikhil I Khushalani, Theresa Medina, Michael E Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik Dec 2022

Efficacy And Safety Of Lifileucel, A One-Time Autologous Tumor-Infiltrating Lymphocyte (Til) Cell Therapy, In Patients With Advanced Melanoma After Progression On Immune Checkpoint Inhibitors And Targeted Therapies: Pooled Analysis Of Consecutive Cohorts Of The C-144-01 Study, Jason Chesney, Karl D Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q Phan, John M Kirkwood, Jessica C Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J S Furness, Nikhil I Khushalani, Theresa Medina, Michael E Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik

Department of Medical Oncology Faculty Papers

Background: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.

Methods: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing …


Determining Front-Line Therapeutic Strategy For Metastatic Clear Cell Renal Cell Carcinoma, Kevin K Zarrabi, Oladimeji Lanade, Daniel M Geynisman Sep 2022

Determining Front-Line Therapeutic Strategy For Metastatic Clear Cell Renal Cell Carcinoma, Kevin K Zarrabi, Oladimeji Lanade, Daniel M Geynisman

Department of Medical Oncology Faculty Papers

The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing immune checkpoint blockade and anti-angiogenesis targeted therapy. Since 2018, we have gained regulatory approval for four distinct combination therapies, all with survival benefits, and with guideline recommendation for use in the front-line setting. As such, treatment selection has become increasingly complex with a myriad of treatment choices but little high-level head-to-head data to guide treatment selection. Heterogeneity in tumor biology further complicates treatment selection as tumors vary in behavior and treatment responsiveness. Ongoing development …


Is Timing Of Steroid Exposure Prior To Immune Checkpoint Inhibitor Initiation Associated With Treatment Outcomes In Melanoma? A Population-Based Study, Nikita Nikita, Joshua Banks, Scott W. Keith, Andrew Song, Jennifer M. Johnson, Melissa Wilson, Swapnil Sharma, Grace Lu-Yao Mar 2022

Is Timing Of Steroid Exposure Prior To Immune Checkpoint Inhibitor Initiation Associated With Treatment Outcomes In Melanoma? A Population-Based Study, Nikita Nikita, Joshua Banks, Scott W. Keith, Andrew Song, Jennifer M. Johnson, Melissa Wilson, Swapnil Sharma, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after …


Targeting Angiogenesis In Squamous Cell Carcinoma Of The Head And Neck: Opportunities In The Immunotherapy Era, Nabil Saba, Pooja Vijayvargiya, Jan Vermorken, Juan Rodrigo, Stefan Willems, Nina Zidar, Remco De Bree, Antti Mäkitie, Greg Wolf, Athanassios Argiris, Yong Teng, Alfio Ferlito Feb 2022

Targeting Angiogenesis In Squamous Cell Carcinoma Of The Head And Neck: Opportunities In The Immunotherapy Era, Nabil Saba, Pooja Vijayvargiya, Jan Vermorken, Juan Rodrigo, Stefan Willems, Nina Zidar, Remco De Bree, Antti Mäkitie, Greg Wolf, Athanassios Argiris, Yong Teng, Alfio Ferlito

Department of Medical Oncology Faculty Papers

Despite the lack of approved anti-angiogenic therapies in squamous cell carcinoma of the head and neck (SCCHN), preclinical and more recent clinical evidence support the role of targeting the vascular endothelial growth factor (VEGF) in this disease. Targeting VEGF has gained even greater interest following the recent evidence supporting the role of immunotherapy in the management of advanced SCCHN. Preclinical evidence strongly suggests that VEGF plays a role in promoting the growth and progression of SCCHN, and clinical evidence exists as to the value of combining this strategy with immunotherapeutic agents. Close to 90% of SCCHNs express VEGF, which has …


Multicenter, Double-Blind, Placebo-Controlled Trial Of Seviprotimut-L Polyvalent Melanoma Vaccine In Patients With Post-Resection Melanoma At High Risk Of Recurrence, Craig L Slingluff, Karl D Lewis, Robert Andtbacka, John Hyngstrom, Mohammed Milhem, Svetomir N Markovic, Tawnya Bowles, Omid Hamid, Leonel Hernandez-Aya, Joel Claveau, Sekwon Jang, Prejesh Philips, Shernan G Holtan, Montaser F Shaheen, Brendan Curti, William Schmidt, Marcus O Butler, Juan Paramo, Jose Lutzky, Arvinda Padmanabhan, Sajeve Thomas, Daniel Milton, Andrew Pecora, Takami Sato, Eddy Hsueh, Suprith Badarinath, John Keech, Sujith Kalmadi, Pallavi Kumar, Robert Weber, Edward Levine, Adam Berger, Anna Bar, J Thaddeus Beck, Jeffrey B Travers, Catalin Mihalcioiu, Brian Gastman, Peter Beitsch, Suthee Rapisuwon, John Glaspy, Edward C Mccarron, Vinay Gupta, Deepti Behl, Brent Blumenstein, Joanna J Peterkin Oct 2021

Multicenter, Double-Blind, Placebo-Controlled Trial Of Seviprotimut-L Polyvalent Melanoma Vaccine In Patients With Post-Resection Melanoma At High Risk Of Recurrence, Craig L Slingluff, Karl D Lewis, Robert Andtbacka, John Hyngstrom, Mohammed Milhem, Svetomir N Markovic, Tawnya Bowles, Omid Hamid, Leonel Hernandez-Aya, Joel Claveau, Sekwon Jang, Prejesh Philips, Shernan G Holtan, Montaser F Shaheen, Brendan Curti, William Schmidt, Marcus O Butler, Juan Paramo, Jose Lutzky, Arvinda Padmanabhan, Sajeve Thomas, Daniel Milton, Andrew Pecora, Takami Sato, Eddy Hsueh, Suprith Badarinath, John Keech, Sujith Kalmadi, Pallavi Kumar, Robert Weber, Edward Levine, Adam Berger, Anna Bar, J Thaddeus Beck, Jeffrey B Travers, Catalin Mihalcioiu, Brian Gastman, Peter Beitsch, Suthee Rapisuwon, John Glaspy, Edward C Mccarron, Vinay Gupta, Deepti Behl, Brent Blumenstein, Joanna J Peterkin

Department of Medical Oncology Faculty Papers

Background: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here.

Methods: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For …


Phase 1 Study Of Safety, Tolerability And Immunogenicity Of The Human Telomerase (Htert)-Encoded Dna Plasmids Ino-1400 And Ino-1401 With Or Without Il-12 Dna Plasmid Ino-9012 In Adult Patients With Solid Tumors, Robert H Vonderheide, Kimberly A Kraynyak, Anthony F Shields, Autumn J Mcree, Jennifer Johnson, Weijing Sun, Ashish V Chintakuntlawar, Jan Pawlicki, Albert J Sylvester, Trevor Mcmullan, Robert Samuels, Joseph J Kim, David Weiner, Jean D Boyer, Matthew P Morrow, Laurent Humeau, Jeffrey M Skolnik Jul 2021

Phase 1 Study Of Safety, Tolerability And Immunogenicity Of The Human Telomerase (Htert)-Encoded Dna Plasmids Ino-1400 And Ino-1401 With Or Without Il-12 Dna Plasmid Ino-9012 In Adult Patients With Solid Tumors, Robert H Vonderheide, Kimberly A Kraynyak, Anthony F Shields, Autumn J Mcree, Jennifer Johnson, Weijing Sun, Ashish V Chintakuntlawar, Jan Pawlicki, Albert J Sylvester, Trevor Mcmullan, Robert Samuels, Joseph J Kim, David Weiner, Jean D Boyer, Matthew P Morrow, Laurent Humeau, Jeffrey M Skolnik

Department of Medical Oncology Faculty Papers

BACKGROUND: Human telomerase reverse transcriptase (hTERT) is frequently classified as a 'universal' tumor associated antigen due to its expression in a vast number of cancers. We evaluated plasmid DNA-encoded hTERT as an immunotherapy across nine cancer types.

METHODS: A phase 1 clinical trial was conducted in adult patients with no evidence of disease following definitive surgery and standard therapy, who were at high risk of relapse. Plasmid DNA encoding one of two hTERT variants (INO-1400 or INO-1401) with or without plasmid DNA encoding interleukin 12 (IL-12) (INO-9012) was delivered intramuscularly concurrent with the application of the CELLECTRA constant-current electroporation device …


Discordant Responses Between Primary Head And Neck Tumors And Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation Of Radiographic And Pathologic Treatment Effect., Dante J. Merlino, Jennifer M. Johnson, Madalina Tuluc, Stacey Gargano, Robert Stapp, Larry Harshyne, Benjamin E. Leiby, Adam Flanders, Ralph Zinner, Rita Axelrod, Joseph Curry, David M. Cognetti, Kyle Mannion, Young J. Kim, Ulrich Rodeck, Athanassios Argiris, Adam J. Luginbuhl Dec 2020

Discordant Responses Between Primary Head And Neck Tumors And Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation Of Radiographic And Pathologic Treatment Effect., Dante J. Merlino, Jennifer M. Johnson, Madalina Tuluc, Stacey Gargano, Robert Stapp, Larry Harshyne, Benjamin E. Leiby, Adam Flanders, Ralph Zinner, Rita Axelrod, Joseph Curry, David M. Cognetti, Kyle Mannion, Young J. Kim, Ulrich Rodeck, Athanassios Argiris, Adam J. Luginbuhl

Department of Medical Oncology Faculty Papers

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.

Patients and Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent …


Relating The Gut Metagenome And Metatranscriptome To Immunotherapy Responses In Melanoma Patients., Brandilyn A. Peters, Melissa Wilson, Una Moran, Anna Pavlick, Allison Izsak, Todd Wechter, Jeffrey S. Weber, Iman Osman, Jiyoung Ahn Oct 2019

Relating The Gut Metagenome And Metatranscriptome To Immunotherapy Responses In Melanoma Patients., Brandilyn A. Peters, Melissa Wilson, Una Moran, Anna Pavlick, Allison Izsak, Todd Wechter, Jeffrey S. Weber, Iman Osman, Jiyoung Ahn

Department of Medical Oncology Faculty Papers

BACKGROUND: Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.

METHODS: In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.

RESULTS: Higher …


First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma., Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A. Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, Simon Khagi, Jana Portnow, Lyndon J. Kim, William G. Loudon, Reid C. Thompson, David E Avigan, Karen L. Fink, Francois J. Geoffroy, Scott Lindhorst, Jose Lutzky, Andrew E. Sloan, Gabriele Schackert, Dietmar Krex, Hans-Jorg Meisel, Julian Wu, Raphael P Davis, Christopher Duma, Arnold B. Etame, David Mathieu, Santosh Kesari, David Piccioni, Manfred Westphal, David S. Baskin, Pamela Z. New, Michel Lacroix, Sven-Axel May, Timothy J. Pluard, Victor Tse, Richard M. Green, John L. Villano, Michael Pearlman, Kevin Petrecca, Michael Schulder, Lynne P Taylor, Anthony E. Maida, Robert M. Prins, Timothy F. Cloughesy, Paul Mulholland, Marnix L. Bosch May 2018

First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma., Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A. Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, Simon Khagi, Jana Portnow, Lyndon J. Kim, William G. Loudon, Reid C. Thompson, David E Avigan, Karen L. Fink, Francois J. Geoffroy, Scott Lindhorst, Jose Lutzky, Andrew E. Sloan, Gabriele Schackert, Dietmar Krex, Hans-Jorg Meisel, Julian Wu, Raphael P Davis, Christopher Duma, Arnold B. Etame, David Mathieu, Santosh Kesari, David Piccioni, Manfred Westphal, David S. Baskin, Pamela Z. New, Michel Lacroix, Sven-Axel May, Timothy J. Pluard, Victor Tse, Richard M. Green, John L. Villano, Michael Pearlman, Kevin Petrecca, Michael Schulder, Lynne P Taylor, Anthony E. Maida, Robert M. Prins, Timothy F. Cloughesy, Paul Mulholland, Marnix L. Bosch

Department of Medical Oncology Faculty Papers

BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax

METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly …


In Vitro Methods For Generating Highly Purified Ebv Associated Tumor Antigen-Specific T Cells By Using Solid Phase T Cell Selection System For Immunotherapy, Jongming Li, Bijoyesh Mookerjee, John Wagner, Neal Flomenberg Dec 2007

In Vitro Methods For Generating Highly Purified Ebv Associated Tumor Antigen-Specific T Cells By Using Solid Phase T Cell Selection System For Immunotherapy, Jongming Li, Bijoyesh Mookerjee, John Wagner, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Adoptive cell transfer immunotherapy has been utilized to treat EBV related human malignancies including post-transplant lymphoproliferative diseases, Hodgkin's lymphoma and nasopharyngeal carcinoma. However, there are limited options available for tumor antigen-specific T cell purification. Here we describe a novel solid phase T cell selection system, in which monocytes or EBV transformed B-lymphocytes are immobilized on solid support for antigen-specific T cell purification. We hypothesize and prove that antigen-specific T cells recognize their cognate antigens and bind to them faster than non-antigen specific T cells. Therefore antigen-specific T cells can be concentrated on the surface after removing the non-adherent cells by …