Neoplasms

All Conditions

Rare Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Vaccines

Immunomodulating Agents

surgery+radiotherapy+chemotherapy+tumor vaccine

tumor vaccine

Di Chen, MD

Glioma patients have poor prognosis because of limited choices of treatment. Therapeutic cancer vaccines have been proved to improve survival in glioma, but resistance is a new challenge for vaccine treatment, and the mechanism is unclear. The applicant found in previous papers that glioma cells induced B7-H4 overexpression in macrophages, and the expression level of B7-H4 is highly correlated with vaccine resistance. Preliminary experiments indicated that B7-H4 protein in macrophages inhibited the expression of ATF3, STAT1 and CXCL9/10, which also resulted in decreased T cell infiltration in glioma model of mouse and was a negative factor of vaccine benefits. Therefore, the applicant hypothesize that B7-H4 inhibits STAT1 transcription by reducing expression of ATF3, resulting in decreased phosphorylated-STAT1 in nucleus, which inhibiting expression and secretion of chemokines 9/10. Thereby, reduced infiltration of T cells in microenvironment will be followed, which ultimately promotes resistance of vaccine treatment in glioma. The follow-up plan of this project will be conducted based on the cells, organoid platform and animal experiments to confirm the role and mechanism of macrophage-derived B7-H4 in secretion of chemokines for T cells and treatment resistance of vaccines. Moreover, the DC vaccine produced by team of the applicant will be used to assess the probability of reversing vaccine resistance when intervening B7-H4 axis. Finally, a model for evaluating clinical benefits from vaccine will be established based on data from clinical trials combining with expression of B7-H4 and clinicopathologic features. This study will provide new evidences for the treatment of cancer vaccines in gliomas.

The Role of B7-H4 in Tumor Vaccine

The Role and Mechanism of B7-H4/ATF3 Axis From Glioma Associated Macrophages in Treatment Resistance of Cancer Vaccine

Different expression level of proteins (CD3,CD8,B7-H4 et.ac) in Gliomas with different grades and molecular subgroups (100 cases) will be measured using immunohistochemical.

The issues collected will be used for transcriptome sequencing to measure gene expression level.

The issues collected will be used for TCR/BCR sequencing to measure clonality of lymphocytes

The issues collected will be used for proteomic sequencing to measure gene expression level in protein

The features from images will be extracted using algorithm of Deep-learning or Radiomics

The issues collected will be used for whole genome sequencing or whole exome sequencing to measure gene mutations.

Huashan Hospital

Professor

Blood and Lymph Conditions

Hematologic Neoplasms

Hematologic Diseases

Part A will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of SRF231 as a monotherapy in patients with advanced solid tumors and lymphoma/Chronic lymphocytic leukemia.

Depending upon the results from Part A of the study and the decision from the Safety Review Committee, 1 or 2 doses or dosing frequencies of SRF231 in select advanced solid and hematologic malignancies.

SRF231 specifically blocks the interaction between CD47 and signal regulatory protein alpha and acts as a potent enhancer of human tumor cell phagocytosis.

SRF231

Robert Ross, MD

This Phase 1/1b, open-label, first-in-human, monotherapy study will be conducted in 2 parts. Part A will consist of the SRF231 monotherapy dose-escalation portion of the study, and will enroll up to 48 patients with advanced solid tumors and hematological cancers. Part B will include monotherapy expansion cohorts in advanced solid and hematologic cancers to further examine SRF231 as monotherapy (100 patients total).

This first-in-human study is designed to evaluate the safety and tolerability of SRF231 as a monotherapy via dose escalation (Part A), and to determine the dose(s) of SRF231 to be further examined in expansion cohorts as monotherapy. The preliminary clinical activity of SRF231 administered as monotherapy will be characterized, along with pharmacokinetics (PK) and pharmacodynamics. In Part B, the safety and tolerability of SRF231 as monotherapy will be evaluated in select patient cohorts of advanced cancers and evaluate clinical activity. The study also is designed to examine the effect of SRF231 monotherapy on peripheral blood immune cell subsets, peripheral blood gene expression, and serum biomarkers

This Phase 1/1b, open-label, first-in-human, monotherapy study will be conducted in 2 parts. Part A will consist of the SRF231 monotherapy dose-escalation portion of the study, and will enroll up to 48 patients with advanced solid tumors and lymphoma/CLL.

Part B will include 5 monotherapy expansion cohorts: in advance solid and hematologic cancers (100 patients total).

Study of SRF231 in Patients With Advanced Solid and Hematologic Cancers

A Phase 1 Study of SRF231 in Patients With Advanced Solid and Hematologic Cancers

The number of patients in Part A who experienced a DLT during Cycle 1 or completed at least 75% of the prescribed Cycle 1 SRF231 dose will be used to assess tolerability and determine the appropriate dose for Part B.

For Part A, the NTD is the dose level at which 2 or more patients experience a DLT in the first cycle of treatment.

For Part A, the MTD is defined as the dose level immediately below the non-tolerated dose (NTD). A total of 6 patients must be treated at a dose level for it to be considered the MTD.

Safety and tolerability of SRF231 monotherapy will be assessed by summarizing adverse events (AEs) and will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE that emerges or worsens in the period from the first dose of study treatment to 30 days after the last dose of study drug assessed by per CTCAE version 4.03 or higher.

Cmax in serum for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods.

Tmax in serum for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods.

AUC 0-last for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods

AUC 0-INF for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods.

T1/2 for all patients who receive at least one dose of SRF231 and had at least one measurable concentration based on the actual sample collection times determined using standard noncompartmental methods.

Blood samples will be collected from all patients at multiple time points for analysis of CD47 receptor occupancy by SRF231. PD analyses will be descriptive and summary tabulations may be produced.

Determine the incidence of ADAs in all patients who receive at least one dose of SRF231 and had at least one measurable sample.

ORR will be estimated by the percentage of patients achieving a best overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, International Working Group Lugano Criteria (IWG Lugano) or other tumor-appropriate response criteria.

DoR defined as the time from first documented response to documented disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, International Working Group Lugano Criteria (IWG Lugano) or other tumor-appropriate response criteria will be summarized.

DCR defined as the percentage of patients with CR, PR or SD determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, International Working Group Lugano Criteria (IWG Lugano) or other tumor-appropriate response criteria will be summarized.

PFS defined as the time from the first treatment on study to death or documented disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, International Working Group Lugano Criteria (IWG Lugano) or other tumor-appropriate response criteria will be summarized.

Surface Oncology

Glioblastoma

Astrocytoma

Histological samples from 10 GBM removed from patients with long-term survival and 10 GBM removed from patients with short-term survival

no intervention

Despite advances in neurosurgery , radiotherapy and chemotherapy, the median survival in GBM patients is only 15 months from diagnosis. Immunotherapy by checkpoint inhibitors (PD1 /PDL-1) appears as a promising treatment for many cancers. However, first clinical results are disappointing for GBM. An hypothesis is the immunosuppressive activity from infiltrating non-tumor cells. Conversion of non-tumor cells from an immunosuppressive to an immuno-activating phenotype could be attempted in a therapeutic perspective.

An important and constant infiltration of cells marked with CD45 has been observed in 77 GBM studied for the prognostic value of PDL1 and IL17 infiltration (in association with Pr Ghiringhelli ; INSERM ; Dijon) . However, CD45 is present at the surface of all leucocytes. The purpose of this project is to better characterize the nature and functionality of the CD45+ cells that infiltrate GBM (lymphocytes and their sub-types, macrophages, microglial cells). Formalin-fixed paraffin-embedded GBM samples will be studied. A panel of immune cell antibody will be used for the immuno-histological (IH) study. Furthermore, the investigator will compare these data with those obtained by the nanoString technology, a multiplexed measurement of gene expression.

Immunological and Functional Characterization of Cellular Population CD45+ Infiltrating Human Glioblastoma

number of cells which express CD45 in the immunological environment from GBM, with using NanoString/RNAseq (NGS) and immunohistology

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Role of B7-H4 in Tumor Vaccine	NCT06156150	Glioma	tumor vaccine	18 Years - 80 Years	Huashan Hospital
Study of SRF231 in Patients With Advanced Solid and Hematologic Cancers	NCT03512340	Advanced Solid ... Hematologic Can...	SRF231	18 Years - 99 Years	Surface Oncology
Study of SRF231 in Patients With Advanced Solid and Hematologic Cancers	NCT03512340	Advanced Solid ... Hematologic Can...	SRF231	18 Years - 99 Years	Surface Oncology
Study of SRF231 in Patients With Advanced Solid and Hematologic Cancers	NCT03512340	Advanced Solid ... Hematologic Can...	SRF231	18 Years - 99 Years	Surface Oncology
Immunological and Functional Characterization of Cellular Population CD45+ Infiltrating Human Glioblastoma	NCT03687099	Glioblastoma	no intervention	18 Years -	Centre Hospitalier Universitaire, Amiens

Spots Global Cancer Trial Database for macrophage

Every month we try and update this database with for macrophage cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for macrophage

Every month we try and update this database with for macrophage cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for macrophage cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.