Igor Puzanov

Igor Puzanov
Roswell Park Cancer Institute · Department of Medicine

MD, MSCI, FACP

About

428
Publications
56,839
Reads
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39,051
Citations
Additional affiliations
July 2005 - April 2012
Vanderbilt University
Position
  • Professor (Assistant)
August 1992 - June 1998
University of Texas Southwestern Medical Center
Position
  • PhD Student
September 1990 - October 1990
Massachusetts General Hospital
Position
  • Sub-intern
Education
September 2005 - June 2007
Vanderbilt University
Field of study
July 2002 - June 2005
Vanderbilt University
Field of study
  • Hematology/Oncology -Fellowship
July 1998 - June 2001
University of Texas Southwestern Medical Center
Field of study
  • Internal Medicine -Residency

Publications

Publications (428)
Article
Full-text available
The Great Debate session at the 2021 Melanoma Bridge virtual congress (December 2–4) featured counterpoint views from experts on seven important issues in melanoma. The debates considered the use of adoptive cell therapy versus use of bispecific antibodies, mitogen-activated protein kinase (MAPK) inhibitors versus immunotherapy in the adjuvant sett...
Article
Full-text available
Over the past decade, immunotherapy has become an increasingly fundamental modality in the treatment of cancer. The positive impact of immune checkpoint inhibition, especially anti-programmed death (PD)-1/PD-ligand (L)1 blockade, in patients with different cancers has focused attention on the potential for other immunotherapeutic approaches. These...
Article
Purpose: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated anti-tumor activity in preclinical models. The ILLUMINATE-101 phase 1 study explored the safety, dose, efficacy, and immune effects of intra-tumoral (it) tilsotolimod monotherapy in multiple solid tumors. Methods: Patients with a diagn...
Article
Full-text available
BackgroundCIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy which has shown survival benefit as a switch maintenance treatment after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). The primary objective of this trial is to establish the safety and recommended phase II dose (RP2D) of CIMAvax-EGF in c...
Article
Full-text available
Filip Stefanovic,1,2 Andres Gomez-Caminero,3 David M Jacobs,2,4 Poornima Subramanian,2 Igor Puzanov,5,6 Maya R Chilbert,4 Steven G Feuerstein,4 Yan Yatsynovich,6,7 Benjamin Switzer,5 Jerome J Schentag2,4,5 1Department of Biomedical Engineering, University at Buffalo School of Engineering and Applied Sciences, Buffalo, NY, USA; 2CPL Associates LLC,...
Article
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Nonmelanoma skin cancers (NMSCs) are some of the most commonly diagnosed malignancies. In general, early-stage NMSCs have favorable outcomes; however, a small subset of patients develop resistant, advanced, or metastatic disease, or aggressive subtypes that are more challenging to treat successfully. Recently, immune checkpoint inhibitors (ICIs) ha...
Article
Background: Cami, an investigational anti-CD25, pyrrolobenzodiazepine-based antibody drug conjugate, imparts cytotoxicity on CD25+ regulatory T cells (Tregs), leading to immunomodulatory effects (eg, modifying effector T cell [Teff]:Treg intratumoral balance). Objective: Describe the pharmacokinetics (PK) and circulating immune cell profile of Cami...
Article
Background: Adrenergic stress (AS) reduces anti-tumor response by decreasing the frequency and function of CD8+ T- cells in the tumor microenvironment (TME), resulting in an increase in those with an “exhausted” phenotype.1 Additionally, AS increases the quantity and immunosuppressive phenotype of myeloid-derived suppressor cells (MDSC) in the TME....
Article
Background: Effective immune therapies depend on the presence of cytotoxic T-lymphocytes (CTLs) in the tumor microenvironment (TME). Our preclinical data showed synergy between TLR3 ligands and interferon-α (IFN-α) in reprogramming the TME, but not healthy tissues, to selectively enhance CTL attraction, providing rationale for their systemic applic...
Article
e21600 Background: Combination BRAF inhibitor (BRAFi) and MEK inhibitor (MEKi) therapy is a widely accepted treatment option for patients (pts) with BRAF-V600E mutant melanoma. Although effective, these combinations exhibit high rates of adverse events (AEs), with 44% - 66% requiring dose modification or interruption and up to 26% discontinuing due...
Article
Full-text available
Background Targeting the MDM2-p53 interaction using AMG 232 is synergistic with MAPK inhibitors (MAPKi) in preclinical melanoma models. We postulated that AMG 232 plus MAPKi is safe and more effective than MAPKi alone in TP53 -wild type, MAPKi-naïve metastatic melanoma. Methods Patients were treated with increasing (120 mg, 180 mg, 240 mg) oral do...
Article
Full-text available
As part of the 2021 Immunotherapy Bridge virtual congress (December 1–2, Naples, Italy), the Great Debate sessions featured experts who were assigned counter opposing views on four important questions in immunotherapy today. The first topic was whether oncolytic viruses or other specific immunomodulators were the more promising approach for intrale...
Article
Cutaneous melanoma remains the most lethal of the primary cutaneous neoplasms, and although the incidence of primary melanoma continues to rise, the mortality from metastatic disease remains unchanged, in part through advances in treatment. Major developments in immunomodulatory and targeted therapies have provided robust improvements in response a...
Article
Aim: Monitoring treatment of tenosynovial giant cell tumor (TGCT) is complicated by the irregular shape and asymmetrical growth of the tumor. We compared responses to pexidartinib by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with those by tumor volume score (TVS) and modified RECIST (m-RECIST). Materials & methods: MRIs acquired eve...
Article
Full-text available
Over the last few years, numerous clinical trials and real-world experience have provided a large amount of evidence demonstrating the potential for long-term survival with immunotherapy agents across various malignancies, beginning with melanoma and extending to other tumours. The clinical success of immune checkpoint blockade has encouraged incre...
Article
Full-text available
As part of the 2020 Immunotherapy Bridge virtual congress (December 2nd–3rd, Italy), the Great Debate session featured counterpoint views from leading experts on three clinical questions in immunotherapy today. The first of these was whether antitumoral vaccination is still a treatment option. The second topic debated whether anti-programmed death...
Article
Full-text available
The Great Debate session at the 2020 Melanoma Bridge virtual congress (December 3rd–5th, Italy) featured counterpoint views from experts on five specific controversial issues in melanoma. The debates considered whether or not innate immunity is important in the response to cancer and immunotherapy, how useful are the revised American Joint Committe...
Article
Full-text available
Improved understanding of tumor immunology has enabled the development of therapies that harness the immune system and prevent immune escape. Numerous clinical trials and real-world experience has provided evidence of the potential for long-term survival with immunotherapy in various types of malignancy. Recurring observations with immuno-oncology...
Article
Full-text available
Advances in immune checkpoint therapy and targeted therapy have led to improvement in overall survival for patients with advanced melanoma. Single agent checkpoint PD-1 blockade and combination with BRAF/MEK targeted therapy demonstrated benefit in overall survival (OS). Superior response rates have been demonstrated with combined PD-1/CTLA-4 block...
Article
The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from...
Article
Background Electroporated plasmid interleukin-12 (pIL-12-EP; tavokinogene telseplasmid; TAVO) induces sustained intratumoral expression of IL-12, a cytokine that is integral for response to anti-PD-1 antibodies. Here, we present updated safety and response duration data from KEYNOTE 695, a Phase 2, multicenter, open-label trial of pIL-12-EP in comb...
Article
Background Mupadolimab (mupa) is a humanized FcγR binding-deficient IgG1 anti-CD73 antibody that has agonistic properties. ¹ CD73 is involved in production of adenosine and in cellular trafficking. Mupa reacts with the majority of circulating B cells leading to activation and expression of differentiation markers CD69, CD138 and CD38, and transform...
Article
Background While IL-2 and IL-15 signal through the shared IL-2/15 βγ receptor, IL-15 does not directly expand regulatory T cells (Tregs)or mediate activation-induced cell death and may have an improved therapeutic index. KD033 is a fusion antibody combining a fully human, high affinity anti-human Programmed Death Ligand 1 (PD-L1) IgG1 antibody with...
Article
Background Combination nivolumab plus ipilimumab was efficacious in patients with asymptomatic melanoma brain metastases (MBM) in CheckMate 204, but showed low efficacy in patients with symptomatic MBM. Here, we provide final 3-year follow-up data from the trial. Methods This open-label, multicentre, phase 2 study (CheckMate 204) included adults (...
Article
Background Intratumoral (IT) cancer therapies may enhance T cell activation and tumor infiltration when combined with systemic checkpoint blockade. This approach may improve treatment of advanced breast cancer, which is commonly resistant to immune therapy. Methods A multicenter basket-style trial ( NCT02643303 ) was performed in patients with adv...
Article
Background ONCR-177 is a recombinant oncolytic herpes simplex virus (oHSV) that retains γ34.5 and is engineered to express five immunomodulatory transgenes (IL-12, FLT3LG ECD, CCL4 and anti-PD-1 and anti-CTLA-4 antibodies) for the intratumoral treatment of solid tumors. Attenuation by miRNA leads to selective replication in tumor cells, and mutatio...
Article
Purpose: To assess the response to pexidartinib treatment in 6 cohorts of adult patients with advanced, incurable solid tumors associated with colony-stimulating factor 1 receptor (CSF1R) and/or KIT proto-oncogene receptor tyrosine kinase activity. Experimental design: From this 2-part phase 1, multicenter study, pexidartinib, a small molecule t...
Article
Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic p...
Article
Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic p...
Article
An unmet need remains for novel immune checkpoint inhibitor combinations that achieve durable and deep responses in patients with metastatic melanoma, without adding substantial toxicity.BEMPEG plus NIVO was well tolerated, and patients achieved deep and durable clinical responses, with a high rate of complete responses (34.2%) and a median progres...
Article
Full-text available
The clinical and immunologic implications of the SARS-CoV-2 pandemic for patients with cancer receiving systemic anticancer therapy have introduced a multitude of clinical challenges and academic controversies. This review summarizes the current evidence, discussion points, and recommendations regarding the use of immune checkpoint inhibitors (ICIs...
Article
Full-text available
Advances in immune checkpoint therapy and targeted therapy have led to improvement in overall survival for patients with advanced melanoma. Single agent checkpoint PD-1 blockade and combination with BRAF/MEK targeted therapy demonstrated benefit in overall survival (OS). Superior response rates have been demonstrated with combined PD-1/CTLA-4 block...
Article
Full-text available
Background Immune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associ...
Article
Full-text available
Immune checkpoint inhibitors (ICIs) are the standard of care for the treatment of several cancers. While these immunotherapies have improved patient outcomes in many clinical settings, they bring accompanying risks of toxicity, specifically immune-related adverse events (irAEs). There is a need for clear, effective guidelines for the management of...
Article
2556 Background: Depletion of tumor-infiltrating CD25+ regulatory T cells (T regs ), which inhibit tumor-specific immune responses, could contribute to tumor eradication. Cami (ADCT-301), an anti-CD25, pyrrolobenzodiazepine-based antibody-drug conjugate, targets CD25+ T regs . A mouse surrogate has shown potent antitumor activity in solid tumor mod...
Article
2568 Background: IL-2 and IL-15 signal through the shared IL-2/15 βγ receptor, but unlike IL-2, IL-15 does not expand regulatory T cells (Tregs), does not mediate activation-induced cell death and may have an improved therapeutic index. KD033 is a fusion antibody combining a fully human, high affinity anti-human Programmed Death Ligand 1 (PD-L1) Ig...
Article
Full-text available
Background In patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients. Methods Patients with measurable MBM, 0.5–3.0 cm, were enr...
Article
Purpose: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma. Patients and methods: Patients with resectable s...
Article
Many patients with advanced melanoma are resistant to immune checkpoint inhibition. In the ILLUMINATE-204 phase 1/2 trial, we assessed intratumoral tilsotolimod, an investigational Toll-like receptor 9 agonist, with systemic ipilimumab in patients with anti-PD-1-resistant advanced melanoma. In all patients, 48.4% experienced grade 3/4 treatment-eme...
Article
Full-text available
Immune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers; however, durable response is limited to only a subset of patients. Discovery of blood-based biomarkers that reflect dynamic change of the tumor microenvironment, and predict response to ICI, will markedly improve current treatment regimens. Here, we investigate CX...
Article
Full-text available
Background Axitinib plus pembrolizumab showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in a randomised phase III trial in patients with advanced renal-cell carcinoma (RCC). We report long-term efficacy and safety of the axitinib/pembrolizumab from the phase I trial (NCT021337...
Article
Purpose: Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC) to inform treatment selection but also to identify novel therapeutic targets. We thus sought to profile circulating angiokines in the context of a randomized treatment trial of everolimus versus sunitinib. Experimental design: ASPEN (NCT01108445) was an...
Article
Full-text available
Objective Long-term safety of pembrolizumab in melanoma was analyzed in KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006. Patients and methods Analysis involved patients who received ≥1 pembrolizumab dose. Lead-time bias was addressed via landmark analyses in patients who were progression-free before day 147. Results Adverse events (AEs) were analyzed f...
Article
Full-text available
The Great Debate session at the 2019 Melanoma Bridge congress (December 5-7, Naples, Italy) featured counterpoint views from experts on five topical issues in melanoma. These were whether to choose local intratumoral treatment or systemic treatment, whether patients with stage IIIA melanoma require adjuvant therapy or not, whether treatment is bett...
Article
Background Electroporated plasmid IL-12 (TAVO or tavokinogene telseplasmid) is a novel pro-inflammatory intratumoral therapy with substantial single agent activity in melanoma, which has been shown to synergize with anti-PD-1 antibodies in patients predicted as non-responders to anti-PD-1. 1 2 Interim data from patients with stage III/IV melanoma a...
Article
Background This is the first randomized trial evaluating an oncolytic virus with an immune checkpoint inhibitor in advanced melanoma. Improved objective response rate (ORR) was observed for T-VEC plus IPI compared to IPI alone (39% vs. 18%; OR 2.9; 95% Cl, 1.5–5.5; P=0.002). ¹ At 3-year follow-up, median OS was not reached in either arm (HR, 0.85;...
Article
Full-text available
Background An unmet need exists for novel therapies that produce deep and durable responses in more patients with metastatic melanoma (metMEL). Encouraging clinical activity was observed with the CD122-preferential IL-2 pathway agonist bempegaldesleukin(BEMPEG) plus nivolumab(NIVO) in first-line metMEL in the phase 1/2 PIVOT-02 trial ( NCT02983045...
Article
Purpose: Increased β-adrenergic receptor (β-AR) signaling has been shown to promote the creation of an immunosuppressive tumor microenvironment (TME). Preclinical studies have shown that abrogation of this signaling pathway, particularly β2-AR, provides a more favorable TME that enhances the activity of anti-PD-1 checkpoint inhibitors. We hypothes...
Article
Full-text available
Background: This Phase 1 dose-escalation/expansion study assessed safety/tolerability of sapanisertib, an oral, highly selective inhibitor of mTORC1/mTORC2, in advanced solid tumours. Methods: Eligible patients received increasing sapanisertib doses once daily (QD; 31 patients), once weekly (QW; 30 patients), QD for 3 days on/4 days off QW (QD ×...
Article
Full-text available
The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor...
Article
Purpose: Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment. Experimental design: Prospectively defined retrospective correlative exploratory analyses tested b...
Conference Paper
Background: RGX-104 is a small-molecule LXR agonist that modulates innate immunity via transcriptional activation of the gene. Binding of to its receptor LRP8 robustly inhibits angiogenesis and depletes myeloid derived suppressor cells (MDSC), thereby activating cytotoxic T-lymphocytes. MDSCs are associated with resistance to both checkpoint inhibi...
Conference Paper
While immune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers including non-small cell lung cancer (NSCLC), only a subset of patients receives durable clinical benefit. Discovery of blood-based biomarkers that reflect dynamic change of tumor microenvironment, and predict response to ICI will markedly improve current tre...
Conference Paper
Background: Tilsotolimod, an investigational Toll-like receptor 9 (TLR9) agonist, modulates the tumor immune microenvironment and has single-agent antitumor activity in preclinical models. The ILLUMINATE-101 phase 1b study (NCT03052205) explored the safety, efficacy, and immune effects of intratumoral tilsotolimod in multiple solid tumors. Methods:...
Conference Paper
RGX-104, a first-in-class small-molecule LXR agonist modulates innate immunity and cancer progression via transcriptional activation of . protein suppresses tumor cell invasion and angiogenesis, and also depletes circulating and tumoral myeloid derived suppressor cells (MDSC), leading to T cell activation.A multivariate approach was used to address...
Article
Full-text available
As part of the 2019 Immunotherapy Bridge congress (December 4–5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practi...
Article
Importance The optimal sequencing of immune checkpoint inhibitors and targeted therapy for BRAF V600E/K-mutant melanoma is not well established. Objective To assess the association of BRAF wild-type (WT) or BRAF V600E/K-mutant status and BRAF inhibitor (BRAFi) with or without MEK inhibitor (MEKi) therapy with response to pembrolizumab. Design, Se...