SGN-B7H4V for Advanced Cancers
Recruiting in Palo Alto (17 mi)
+21 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: Seagen Inc.
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests a new drug called SGN-B7H4V for safety and side effects in patients with advanced or metastatic solid tumors. It aims to find the right dosage and see if the drug can effectively treat their cancer.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, it is common for clinical trials to have specific requirements, so it's best to discuss your current medications with the trial coordinators.
What data supports the idea that SGN-B7H4V for Advanced Cancers is an effective treatment?
The available research shows that targeting B7-H4, which is part of the SGN-B7H4V treatment, can help the body's immune system fight cancer more effectively. Studies have found that blocking B7-H4 can restore the body's natural ability to attack cancer cells, especially in ovarian cancer. This is because B7-H4 is found in high levels in many tumors and is linked to aggressive cancer behavior. By using antibodies to block B7-H4, researchers have been able to improve the immune response against tumors, suggesting that SGN-B7H4V could be an effective treatment for advanced cancers.
12345What safety data is available for SGN-B7H4V in advanced cancers?
The provided research does not contain specific safety data for SGN-B7H4V or its evaluations under different names. The studies listed focus on other treatments and their safety profiles in various cancer types.
678910Is the drug SGN-B7H4V a promising treatment for advanced cancers?
Yes, SGN-B7H4V is a promising treatment for advanced cancers because it targets B7-H4, a protein that can help tumors grow by weakening the immune system. By blocking B7-H4, SGN-B7H4V may help the immune system fight cancer more effectively.
1341112Eligibility Criteria
This trial is for adults with advanced solid tumors that are locally advanced, unresectable, or metastatic. Participants must be in good physical condition (ECOG 0 or 1), have measurable disease, and provide tumor tissue. Those with recent other cancers, brain metastases, previous similar treatments, significant neuropathy, or active corneal disease can't join.Inclusion Criteria
My condition has not improved with standard treatments or I cannot tolerate them.
I have a specific type of advanced or metastatic cancer.
I can provide a sample of my tumor for the study.
+2 more
Exclusion Criteria
My cancer has spread to the lining of my brain and spinal cord.
My brain metastases are stable, and I haven't taken corticosteroids for them in the last 7 days.
I have not had any other cancers in the last 3 years, or if I have, they are not likely to spread.
+3 more
Participant Groups
SGN-B7H4V is being tested for safety and effectiveness in treating various solid tumors. The study has three parts: determining the right dose (Parts A & B) and then assessing its safety and how well it works at that dose (Part C).
2Treatment groups
Experimental Treatment
Group I: SGN-B7H4V and Pembrolizumab (Parts D and E)Experimental Treatment2 Interventions
SGN-B7H4V in combination with Pembrolizumab.
Group II: SGN-B7H4V (Parts A, B, and C)Experimental Treatment1 Intervention
SGN-B7H4V monotherapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Northwestern UniversityChicago, IL
McGill University Department of Oncology / McGill University Health CentreMontreal, Canada
University of Ottawa / Ottawa General HospitalOttawa, Canada
SCRI Oncology PartnersNashville, TN
More Trial Locations
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Who Is Running the Clinical Trial?
Seagen Inc.Lead Sponsor
References
The prognostic impact of B7-H3 and B7-H4 in head and neck squamous cell carcinoma. [2023]Immune checkpoint inhibition is a therapeutic option in many cancer entities. In head and neck squamous cell carcinoma (HNSCC) targeting of the PD-1/PD-L1 (B7-H1) axis is approved in recurrent/metastatic disease and is being explored in the curative setting. Here, we evaluated two related members of the B7 family, B7-H3 & B7-H4, for their prognostic impact under standard treatment.
Novel recombinant human b7-h4 antibodies overcome tumoral immune escape to potentiate T-cell antitumor responses. [2022]B7-H4 (VTCN1, B7x, B7s) is a ligand for inhibitory coreceptors on T cells implicated in antigenic tolerization. B7-H4 is expressed by tumor cells and tumor-associated macrophages (TAM), but its potential contributions to tumoral immune escape and therapeutic targeting have been less studied. To interrogate B7-H4 expression on tumor cells, we analyzed fresh primary ovarian cancer cells collected from patient ascites and solid tumors, and established cell lines before and after in vivo passaging. B7-H4 expression was detected on the surface of all fresh primary human tumors and tumor xenotransplants, but not on most established cell lines, and B7-H4 was lost rapidly by tumor xenograft cells after short-term in vitro culture. These results indicated an in vivo requirement for B7-H4 induction and defined conditions for targeting studies. To generate anti-B7-H4-targeting reagents, we isolated antibodies by differential cell screening of a yeast-display single-chain fragments variable (scFv) library derived from patients with ovarian cancer. We identified anti-B7-H4 scFv that reversed in vitro inhibition of CD3-stimulated T cells by B7-H4 protein. Notably, these reagents rescued tumor antigen-specific T-cell activation, which was otherwise inhibited by coculture with antigen-loaded B7-H4+ APCs, B7-H4+ tumor cells, or B7-H4- tumor cells mixed with B7-H4+ TAMs; peritoneal administration of anti-B7-H4 scFv delayed the growth of established tumors. Together, our findings showed that cell surface expression of B7-H4 occurs only in tumors in vivo and that antibody binding of B7-H4 could restore antitumor T-cell responses. We suggest that blocking of B7-H4/B7-H4 ligand interactions may represent a feasible therapeutic strategy for ovarian cancer.
Potential targeting of B7-H4 for the treatment of cancer. [2022]Observations noting the presence of white blood cell infiltrates within tumors date back more than a century, however the cellular and molecular mechanisms regulating tumor immunity continue to be elucidated. The recent successful use of monoclonal antibodies to block immune regulatory pathways to enhance tumor-specific immune responses for the treatment of cancer has encouraged the identification of additional immune regulatory receptor/ligand pathways. Over the past several years, a growing body of data has identified B7-H4 (VTCN1/B7x/B7S1) as a potential therapeutic target for the treatment of cancer. The potential clinical significance of B7-H4 is supported by the high levels of B7-H4 expression found in numerous tumor tissues and correlation of the level of expression on tumor cells with adverse clinical and pathologic features, including tumor aggressiveness. The biological activity of B7-H4 has been associated with decreased inflammatory CD4+ T-cell responses and a correlation between B7-H4-expressing tumor-associated macrophages and FoxP3+ regulatory T cells (Tregs) within the tumor microenvironment. Since B7-H4 is expressed on tumor cells and tumor-associated macrophages in various cancer types, therapeutic blockade of B7-H4 could favorably alter the tumor microenvironment allowing for antigen-specific clearance tumor cells. The present review highlights the therapeutic potential of targeting B7-H4.
Isolation and Validation of Anti-B7-H4 scFvs from an Ovarian Cancer scFv Yeast-Display Library. [2015]B7-H4 (VTCN1, B7x, B7s) is an inhibitory modulator of T-cell response implicated in antigen tolerization. As such, B7-H4 is an immune checkpoint of potential therapeutic interest. To generate anti-B7-H4 targeting reagents, we isolated antibodies by differential cell screening of a yeast-display library of recombinant antibodies (scFvs) derived from ovarian cancer patients and we screened for functional scFvs capable to interfere with B7-H4-mediated inhibition of antitumor responses. We found one antibody binding to B7-H4 that could restore antitumor T cell responses. This chapter gives an overview of the methods we developed to isolate a functional anti-B7-H4 antibody fragment.
Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. [2019]This phase I study evaluated nivolumab combined with erlotinib in patients with advanced EGFR-mutant NSCLC.
Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors. [2022]Study objectives included evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of VX15/2503 in advanced solid tumor patients.
Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. [2021]Preclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed or refractory B-cell malignant diseases.
A phase I trial to determine the safety, pharmacokinetics, and pharmacodynamics of intercalated BMS-690514 with paclitaxel/carboplatin (PC) in advanced or metastatic solid malignancies. [2015]A phase I dose escalation study was performed to determine the maximum tolerated dose (MTD) of intercalated dosing of BMS-690514, a reversible oral panHER/VEGF receptor inhibitor, combined with paclitaxel/carboplatin (PC) in advanced solid tumors. Secondary endpoints included safety, pharmacokinetics (PK), exploratory pharmacodynamics (PD), and preliminary efficacy.
Controlling tumor invasion: bevacizumab and BMP4 for glioblastoma. [2015]Bevacizumab has been reported to result in increased tumor invasion when used to treat malignant glioma. We hypothesized that BMP4 would prevent diffuse tumor infiltration induced by bevacizumab for malignant glioma in a xenograft model.
Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. [2022]Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is necessary to investigate the safety and efficacy of Ate/Bev in real settings.
B7-H4 is a positive regulator of antitumor immunity. [2022]B7-H4 (B7x, B7S1, VTCN1, DD-0110) is a member of the B7 superfamily that negatively regulates T cell responses.1 In addition, B7-H4 expression is increased on tumors and has been shown to be a negative prognostic marker for many cancers.2 Unexpectedly our recent study demonstrated that B7-H4 inhibited tumor growth and was required to promote effective antitumor responses.3.
Serum B7-H4 expression is a significant prognostic indicator for patients with gastric cancer. [2022]B7-H4 is a novel B7 ligand that plays an important role in the T cell-mediated immune response as a negative regulator. Previous studies have suggested the aberrant expression of membrane B7-H4 in tumor cells. The aim of this study is to determine the expression levels of preoperative soluble B7-H4 (sB7-H4) in circulation and to investigate the correlations between sB7-H4 levels and clinicopathological parameters as well as the survival rate of patients with gastric cancer.