A5026470012- Cancer Immunotherapy and Biomarkers
- Sarcoma Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Neuroblastoma Research and Treatments
- Neurofibromatosis and Schwannoma Cases
- Lung Cancer Treatments and Mutations
- Gastric Cancer Management and Outcomes
- Cancer-related molecular mechanisms research
- Glioma Diagnosis and Treatment
- Cutaneous lymphoproliferative disorders research
- Adenosine and Purinergic Signaling
- Esophageal Cancer Research and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Cancer Cells and Metastasis
- Cancer, Stress, Anesthesia, and Immune Response
- Beetle Biology and Toxicology Studies
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- Cardiac tumors and thrombi
- Autophagy in Disease and Therapy
- Colorectal and Anal Carcinomas
- Metastasis and carcinoma case studies
Columbia University Irving Medical Center
2019-2024
Columbia University
2024
Herbert Irving Comprehensive Cancer Center
2019-2024
Rabin Medical Center
2015-2017
Importance Combining immune checkpoint blockade (ICB) with chemotherapy improves outcomes in patients metastatic gastric and gastroesophageal junction (G/GEJ) adenocarcinoma; however, whether this combination has activity the perioperative setting remains unknown. Objective To evaluate safety preliminary of ICB followed by maintenance resectable G/GEJ adenocarcinoma. Design, Setting, Participants This investigator-initiated, multicenter, open-label, single-stage, phase 2 nonrandomized...
Abstract Background: Perioperative therapy for locally advanced (LA) GC/GEJ adenocarcinoma is standard of care. Although immune checkpoint blockade (ICB) following chemoradiotherapy and resection significantly improves disease free survival (DFS) esophageal cancer, the effectiveness ICB together with chemotherapy in LA cancer unknown. Methods: This a multicenter, single-arm, phase II clinical trial pembrolizumab 200 mg every 3 weeks capecitabine 625 mg/m2 twice daily oxaliplatin 130 (CAPOX)...
11565 Background: Cytotoxic chemotherapy in patients (pts) with unresectable malignant peripheral nerve sheath tumors (MPNSTs) affords minimal benefit significant toxicity. Pexidartinib, an inhibitor of colony-stimulating factor-1 receptor (CSF1R), targets infiltrating M2 macrophages which correlate disease progression; combination mTOR resulted sustained tumor control our xenograft MPNST model. A phase I study pexidartinib + sirolimus suggested the combination’s safety and tumoral static...
Abstract Purpose: To evaluate sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTK), for the treatment well-differentiated/dedifferentiated liposarcoma (WD/DD LPS). Patients and Methods: This multicenter, open-label, Phase II trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen progression within 12 weeks enrollment. sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon two-stage design was used improvement in...
TPS4200 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a uniformly fatal disease for which treatments result in limited benefit. Failure of immune checkpoint blockade attributed to multiple immunosuppressive pathways within the tumor microenvironment. The C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C ligand 12 (CXCL12) axis results exclusion anti-tumor cells. Preclinical studies demonstrated that simultaneous CXCR4 inhibition (CXCR4i) and anti-programmed cell death 1...
10075 Background: Uveal melanomas (UM) measuring at least 12mm in base diameter with a class 2 signature as defined by gene expression profiling (DecisionDx-UM) are characterized high metastatic risk, median time to recurrence of 32 months. No therapy has been shown reduce this risk. The growth factor receptor Met is highly expressed UM. We have previously that crizotinib, an inhibitor Met, effective adjuvant preclinical models (Surriga et al, Mol Cancer Ther 2013). therefore conducted phase...
The aim of the present phase I first‑in‑human study was to investigate safety/efficacy dTCApFs (a novel hormone peptide that enters cells through T1/ST2 receptor), in advanced/metastatic solid tumors. primary objective this open‑label dose‑escalation determine safety profile dTCApFs. enrolled patients (aged ≥18 years) with pathologically confirmed locally malignancies, who experienced treatment failure or were unable tolerate previous standard therapy. included 17 (64% male; median age, 65...
11055 Background: No effective therapy exists for unresectable malignant peripheral nerve sheath tumors (MPNSTs). We previously reported that the combination of PEX and mTOR inhibitor S synergistically inhibited MPNST growth (CCR 20: 3146, 2014) by depleting M2 TAMs inhibiting receptor tyrosine kinases (RTKs), including c-KIT, PDGFR, CSF1R. characterized safety, tolerability, recommended phase 2 dose (RP2D) plus in all sarcoma sub-types. Methods: Patients (pts) received orally 28 days cycle...
5082 Background: Immunotherapy has limited efficacy in castration-resistant prostate cancer. Androgen deprivation therapy (ADT) significant immunomodulatory effects and initially induces a complex immune infiltrate before castration-resistance develops. However, ADT also recruits immunosuppressive myeloid cells to the tumor microenvironment by increasing interleukin-8 (IL-8). We conducted phase Ib/II clinical trial of immunotherapy plus men with recurrent castration-sensitive cancer (CSPC)....
Abstract Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a uniformly fatal disease. Immune checkpoint inhibitors have thus far failed to improve outcomes due an immunosuppressive tumor microenvironment (TME). In preclinical mouse models, signaling through the C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C ligand 12 (CXCL12) axis results in exclusion of anti-tumor immune cells. Using KPC PDAC model, we demonstrated that treatment with combination CXCR4 inhibitor (CXCR4i),...
TPS714 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease for which immune checkpoint blockade (ICB) has not provided benefit, hypothesized to be due the presence of immunosuppressive tumor microenvironment (TME). Neoadjuvant multi-agent chemotherapy and stereotactic body radiation therapy (SBRT) may increase immunosuppression by elevating intratumoral levels adenosine, metabolite. Adenosine, produced from adenosine triphosphate enzymes CD39 CD73, binds 2a 2b...
2056 Background: Somatic mutations in isocitrate dehydrogenase 1 (IDH) are recognized as an important prognostic factor patients with gliomas and associated longer survival. Regardless of initial grade, however, recurrence transformation into higher grade tumors is almost universal. IDH-mutant prone to develop hypermutation after exposure alkylating agents; other solid tumors, may be a predictive biomarker for PD-1 inhibitor response. In this multicenter phase 2, open label, single arm...
TPS4208 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) carries a 5-year relative survival of 3%. Immune checkpoint inhibitors have thus far failed to improve outcomes due an immunosuppressive tumor microenvironment (TME). Signaling through the C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C ligand 12 (CXCL12) axis results in exclusion anti-tumor immune cells mouse PDAC models. Longitudinal studies testing combinations CXCR4i, aPD-1, and gemcitabine KPC model demonstrated...
Abstract Combining MEK and autophagy inhibitors in preclinical PDAC mouse models resulted tumor regressions improved rodent survival. These findings provided the rationale for clinical investigation of this combination. The phase 1 MEKiAUTO trial evaluated combination cobimetinib, HCQ, with or without atezolizumab 14 patients (pts) KRAS-mutated pancreatic adenocarcinoma (PDAC). study was closed due to a lack preliminary efficacy poor tolerability; however, three experienced progression free...
Abstract BACKGROUND Somatic mutations in isocitrate dehydrogenase 1 (IDH1) are an important prognostic factor patients with gliomas. IDH-mutant gliomas prone to develop hypermutation after exposure alkylating agents; other solid tumors, may be a predictive biomarker for PD-1 inhibitor response. In this study, we hypothesize that specific subgroup of would clinically benefit from nivolumab as measured by overall response rate (ORR), duration (DOR), median progression-free survival (PFS), and...
e14018 Background: This apoptosis factor (NEROFE) is a 14-a.a. modified form of hormone-like peptide present in the human thymus, which plays key role immune system regulation. In preclinical evaluation, it induced cancer cells, inhibited angiogenesis/metastasis, and showed vivo efficacy with no toxicity. Methods: ongoing, single-center, first-in-human, 3+3 dose-escalation study this given I.V. at 6 mg/m2-96 mg/m2over 5 3-pt cohorts (3 times week; 28-day cycle) examines MTD, safety, PK...
<div>AbstractPurpose:<p>To evaluate sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTK), for the treatment well-differentiated/dedifferentiated liposarcoma (WD/DD LPS).</p>Patients and Methods:<p>This multicenter, open-label, Phase II trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen progression within 12 weeks enrollment. Patients sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon...
<div>AbstractPurpose:<p>To evaluate sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTK), for the treatment well-differentiated/dedifferentiated liposarcoma (WD/DD LPS).</p>Patients and Methods:<p>This multicenter, open-label, Phase II trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen progression within 12 weeks enrollment. Patients sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon...
45 Background: Autophagy, a catabolic cell survival process, is upregulated when cancer cells undergo MEK inhibition (MEKi) in preclinical models of pancreas adenocarcinoma (PDAC), and may function as pathway resistance. Simultaneous the autophagy PDAC has demonstrated anti-tumor immune modulating effects. MEKiAUTO evaluated tolerability safety combination cobimetinib, HCQ, atezolizumab at three dose levels (DL), advanced KRAS-mutated malignancies. Methods: This multicenter phase I study...
11565 Background: Immune checkpoint inhibitors have limited efficacy in soft tissue sarcoma (STS) due to insufficient T-cell activation and infiltration by immunosuppressive macrophages. Sotigalimab (S), a high-affinity humanized monoclonal antibody for CD40, promotes antigen presentation, stimulates responses, reprograms Preclinical studies with CD40 agonists revealed immune “cold” tumor types synergy chemotherapy. Standard first-line doxorubicin (D) provides objective response rate (ORR)...
Abstract Background: Preclinical and clinical studies suggest that trastuzumab resistance in HER2+ BC is mediated by cross-activation of alternative signaling pathways. Computational analysis pooled whole-genome RNAi screens HER2 transformed cell lines identified the IL6/JAK2/STAT3 axis as a master regulator pathway. The combination plus ruxolitinib, JAK1/JAK2 inhibitor, demonstrated synergistic tumor growth inhibition mouse xenografts lines. These data provide rationale for studying...