A Randomized, Open-Label Phase 1/2 Study Evaluating Ramucirumab in Pediatric Patients and Young Adults With Relapsed, Recurrent, or Refractory Synovial Sarcoma

This study is being conducted to test the safety and efficacy of ramucirumab in combination with other chemotherapy in the treatment of relapsed, recurrent, or refractory synovial sarcoma (SS) in children and young adults. This trial is part of the CAMPFIRE master protocol (NCT05999994) which is a platform to accelerate the development of new treatments for pediatric and young adult participants with cancer. Your participation in this trial could last 12 months or longer, depending on how you and your tumor respond.

开始日期2020-03-04

申办/合作机构

Eli Lilly & Co.

NCT04176016 / Terminated临床1期

Safety Study of Radiolabeled (111In or 90Y) OTSA101-DTPA, an Anti-Frizzled Homolog 10 (FZD10) Monoclonal Antibody, to Evaluate Safety and Pharmacokinetics in Patients With Relapsed or Refractory Synovial Sarcoma

The purpose of this study is to evaluate safety and pharmacokinetics as well as the biodistribution of OTSA101-DTPA-111In and to evaluate the safety of intravenous administration of OTSA101-DTPA-90Y.

开始日期2020-01-10

申办/合作机构

OncoTherapy Science, Inc.

NCT03670069 / Terminated临床1期IIT

A Pilot Study Examining the Impact of the Jak1 Inhibitor Itacitinib on the Sarcoma Tumor Immune Microenvironment

This pilot phase I trial studies how well itacitinib works in treating patients with sarcomas that do not respond to treatment (refractory) and have spread to other parts of the body (advanced/metastatic). Itacitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

开始日期2019-09-30

申办/合作机构

Fred Hutchinson Cancer Research Center

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100 项与难治性滑膜肉瘤相关的临床结果

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100 项与难治性滑膜肉瘤相关的转化医学

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0 项与难治性滑膜肉瘤相关的专利（医药）

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项与难治性滑膜肉瘤相关的文献（医药）

2023-06-15·International Journal of Cancer

A phase 1 trial of NY‐ESO‐1‐specific TCR‐engineered T‐cell therapy combined with a lymph node‐targeting nanoparticulate peptide vaccine for the treatment of advanced soft tissue sarcoma

Article

作者: Nagata, Yasuhiro ; Seo, Naohiro ; Kageyama, Shinichi ; Ishihara, Mikiya ; Miyahara, Yoshihiro ; Kakunaga, Shigeki ; Momose, Fumiyasu ; Takada, Kohichi ; Watanabe, Takashi ; Hattori, Hiroyoshi ; Emori, Makoto ; Kitano, Shigehisa ; Harada, Naozumi ; Muraoka, Daisuke ; Matsumine, Akihiko ; Nishida, Yoshihiro ; Endo, Makoto ; Matsumoto, Yoshihiro ; Sasada, Tetsuro ; Shiku, Hiroshi ; Sato, Eiichi ; Yamada, Tomomi ; Kawai, Akira

AbstractThe efficacy of immune checkpoint inhibitors is limited in refractory solid tumors. T‐cell receptor gene‐modified T (TCR‐T)‐cell therapy has attracted attention as a new immunotherapy for refractory cold tumors. We first investigated the preclinical efficacy and mode of action of TCR‐T cells combined with the pullulan nanogel:long peptide antigen (LPA) vaccine in a mouse sarcoma model that is resistant to immune checkpoint inhibition. Without lymphodepletion, the pullulan nanogel:LPA vaccine markedly increased the number of TCR‐T cells in the draining lymph node and tumor tissue. This change was associated with enhanced CXCR3 expression in TCR‐T cells in the draining lymph node. In the phase 1 trial, autologous New York esophageal squamous cell carcinoma 1 (NY‐ESO‐1)‐specific TCR‐T cells were infused twice into HLA‐matched patients with NY‐ESO‐1+ soft tissue sarcoma (STS). The pullulan nanogel:LPA vaccine contains an epitope recognized by TCR‐T cells, and it was subcutaneously injected 1 day before and 7 days after the infusion of TCR‐T cells. Lymphodepletion was not performed. Three patients with refractory synovial sarcoma (SS) were treated. Two out of the three patients developed cytokine release syndrome (CRS) with low‐to‐moderate cytokine level elevation. We found obvious tumor shrinkage lasting for more than 2 years by tumor imaging and long‐term persistence of TCR‐T cells in one patient. In conclusion, NY‐ESO‐1‐specific TCR‐T‐cell therapy plus vaccination with the pullulan nanogel carrying an LPA containing the NY‐ESO‐1 epitope without lymphodepletion is feasible and can induce promising long‐lasting therapeutic effects in refractory SS (Registration ID: JMA‐IIA00346).

2021-11-02·Expert Opinion on Therapeutic Patents2区 · 医学

Recent updates on Wnt signaling modulators: a patent review (2014-2020)

2区 · 医学

Review

作者: Patel, Bhumika D. ; Goswami, Vishalgiri G.

Introduction: Wnt signaling is a signal transduction pathway that plays a vital role in embryonic development and normal tissue preservation. Dysfunction of it gives rise to various diseases like cancer, Alzheimer's, metabolic and skeletal disorders, kidney and liver disease, etc. Thus, targeting Wnt pathway can be a potential approach to design and develop novel therapeutic classes.Areas covered: Authors provided an overview of Wnt modulators from 2014 to 2020. Different heterocyclic scaffolds and their pharmacology from a total of 104 PCT applications have been summarized.Expert opinion: The scientific community is working extensively to bring first in the class molecule to the market which targets Wnt pathway. Lorecivivint, Wnt inhibitor, for the treatment of knee Osteoarthritis and SM-04554, Wnt activator, for the treatment of androgenetic alopecia are currently under Phase III. Other molecules, LGK-974, RXC-004, ETC-159, CGX-1321, PRI-724, CWP-232291 and BC-2059 are also under different stages of clinical development for the treatment of cancer. Antibody based Wnt modulator, OTSA101-DTPA-90Y is currently under Phase I for the treatment of Relapsed or Refractory Synovial Sarcoma while OMP-18R5 is under Phase I for Metastatic Breast Cancer. Ongoing preclinical/clinical trials will define the role of the Wnt pathway in different therapeutic areas and open new opportunities.

2019-12-01·Journal for ImmunoTherapy of Cancer2区 · 医学

Guillain-Barre syndrome observed with adoptive transfer of lymphocytes genetically engineered with an NY-ESO-1 reactive T-cell receptor

2区 · 医学

ArticleOA

作者: Nowell, Erica ; Malik, Karan ; Trinh, Van Anh ; Araujo, Dejka ; Carter, Kristen ; Weathers, Shiao-Pei ; Conley, Anthony P ; Nathenson, Michael J ; Demetri, George D ; Joseph, Jocelyn

BACKGROUNDAdoptive transfer of autologous T-lymphocytes transduced with a high affinity NY-ESO-1-reactive T-cell receptor (NY-ESO-1^c259 T-cells) has emerged as a promising therapeutic strategy for patients with refractory synovial sarcoma. Secondary autoimmune T-cell mediated toxicities can occur long after initial adoptive T-cell transfer. We report on the first two cases of the development and management of Guillain-Barre syndrome in synovial sarcoma patients who received NY-ESO-1^c259 T-cells.CASE PRESENTATIONA 47 year-old woman and 39 year-old woman with refractory metastatic SS were treated with fludarabine-cyclophosphamide lymphodepletion followed by adoptive transfer of NY-ESO-1^c259 T-cells. On day 42 after adoptive T-cell therapy, patient one presented to the emergency room with a one-week history of numbness, paresthesia, and heaviness to both legs progressing to difficulty walking on the day of presentation. Although MRI brain and lumbar puncture were negative, electromyography (EMG) and nerve conduction studies (NCS) of the lower extremities and right arm performed revealed an abnormal study suggestive of a very mild, distal, motor, axonal polyneuropathy. Patient two presented on day 113 with bilateral foot numbness, left foot drop, unsteady gait, and pain in the left thigh, which progressed over two week to bilateral leg weakness, inability to walk, and numbness bilaterally in the hands, legs, and feet. Both patients received intravenous immunoglobulin (IVIG) 0.4 g/kg/day for 5 days for possible acute inflammatory demyelinating polyneuropathy (AIDP) likely related to NY-ESO-1 targeting T-cell therapy. After 3 and 5 doses, respectively, of IVIG, the patients reported improvement in symptoms and strength, and were later transferred to an inpatient rehabilitation facility to continue gaining strength. At patient one's neurology follow-up on day 95, she reported only mild left lower extremity (LLE) weakness and was gradually successfully regaining independence in motor function. At patient two's 9-month follow-up, the patient had regained normal function and independence.CONCLUSIONSGiven the expanding applications of immunotherapy in cancer management, clinicians should stay vigilant against the potential development of unusual but life-threatening immune-mediated toxicities.