MVA p53 vaccine (Tara Immuno-Oncology)(MVA p53 vaccine (Tara Immuno-Oncology)) - 药物靶点：p53_在研适应症：复发性卵巢癌，复发性铂耐药性输卵管癌，复发性铂耐药性卵巢癌_专利_临床

概要

基本信息

药物类型

通用抗原疫苗、治疗性疫苗

别名

p53MVA vaccine Tara ImmmunoOncology、p53MVAvaccine

靶点

p53

作用机制

p53刺激剂(p53蛋白刺激剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [3]

在研适应症

复发性卵巢癌复发性铂耐药性输卵管癌复发性铂耐药性卵巢癌+ [13]

非在研适应症

复发性结肠癌复发性胃癌复发性原发性腹膜癌+ [1]

原研机构

City of Hope National Medical Center

在研机构

National Cancer Institute

City of Hope National Medical Center

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

4

项与 MVA p53 vaccine (Tara Immuno-Oncology) 相关的临床试验

NCT03113487

/ Active, not recruiting临床2期IIT

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

This phase II trial studies how well modified vaccinia virus ankara vaccine expressing p53 (p53MVA) and pembrolizumab work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving p53MVA and pembrolizumab together may work better in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.

开始日期2018-02-01

申办/合作机构

City of Hope National Medical Center

[+1]

NCT02432963

/ Active, not recruiting临床1期IIT

A Phase I Study of a p53MVA Vaccine in Combination With Pembrolizumab

This phase I trial studies the side effects of vaccine therapy and pembrolizumab in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment, that have failed prior therapy, and that cannot be removed by surgery. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving vaccine therapy together with pembrolizumab may be a better treatment in patients with solid tumors.

开始日期2016-06-14

申办/合作机构

City of Hope National Medical Center

[+1]

NCT02275039

/ Completed临床1期IIT

A Phase I Study of a p53MVA Vaccine in Combination With Gemcitabine in Ovarian Cancer

This phase I trial studies the side effects and recommended dose of the combination of p53MVA vaccine (modified vaccinia virus ankara vaccine expressing tumor protein p53 [p53]) and gemcitabine hydrochloride in treating patients with ovarian epithelial cancer that has come back. Vaccines made from inserting a laboratory-treated gene into a person's tumor cells may help the body build an effective immune response to kill tumor cells that express p53. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving modified vaccinia virus ankara vaccine expressing p53 together with gemcitabine hydrochloride may work better in treating patients with ovarian epithelial cancer.

开始日期2015-01-01

申办/合作机构

City of Hope National Medical Center

[+1]

100 项与 MVA p53 vaccine (Tara Immuno-Oncology) 相关的临床结果

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100 项与 MVA p53 vaccine (Tara Immuno-Oncology) 相关的转化医学

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100 项与 MVA p53 vaccine (Tara Immuno-Oncology) 相关的专利（医药）

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8

项与 MVA p53 vaccine (Tara Immuno-Oncology) 相关的文献（医药）

2023-12-20·Cancer Research Communications

Immunologic Signatures of Peripheral Blood T Cells Reveal the Outcome of p53MVA Vaccine and Pembrolizumab Treatment in Patients with Advanced Ovarian Cancer

Article

作者: Dempsey, Shannon ; Ruel, Nora ; Dellinger, Thanh H ; Diamond, Don J ; Frankel, Paul ; Eng, Melissa ; Cristea, Mihaela ; Tinsley, Raechelle ; Kos, Ferdynand J ; Stewart, Daphne

AbstractPurpose:Our previous studies indicated that p53-reactive T cells were associated with clinical benefit in patients with advanced ovarian cancer who were treated with p53-expressing modified vaccinia Ankara (p53MVA) vaccine and gemcitabine chemotherapy. To replace chemotherapy with an approach that will enhance vaccine efficacy and antitumor immunity, we treated patients with p53MVA in combination with PD-1 checkpoint blocker, pembrolizumab. We also attempted to further characterize the activation status of T cells prior to vaccination and during treatment.Experimental Design:Patients received up to three triweekly vaccinations concurrent with pembrolizumab, followed by pembrolizumab monotherapy at 3-week intervals. Correlative studies analyzed peripheral blood T-cell phenotypes and profiles of immune function gene expression.Results:We observed 6/28 (21%) patients with a clinical benefit to therapy, including 3 partial responses (PR) and 3 patients with stable disease (SD) for 6+ months. The median progression-free survival was 1.8 months (95% confidence interval: 1.7–3.8) and median overall survival was 15.1 months (9.4–30.4). Two patients remain progression-free at 28 and 33 months. Of the 18 patients evaluable in correlative studies, 6 were immunologic responders of whom 5 had clinical benefit (3 PR, 2 SD). Immunologic non-responders expressed in pretreatment peripheral blood mononuclear cell samples high levels of mRNA for multiple molecules associated with terminally differentiated T cells.Conclusions:p53MVA/pembrolizumab immunotherapy showed promising antitumor activity in patients who demonstrated functionally competent peripheral blood T cells. Detection of markers of terminally differentiated T cells before treatment may identify patients unlikely to respond to p53MVA/pembrolizumab.Significance:The activity of a combination immunotherapy of p53 vaccine and PD-1 checkpoint blockade in patients with platinum-resistant ovarian cancer was evaluated in a phase II trial. Clinical benefit was correlated with the responsive immune status of patients before and during the treatment, defining potential predictive markers for immune therapy.

2019-03-08·Clinical and Translational Oncology3区 · 医学

Evaluation of safety and efficacy of p53MVA vaccine combined with pembrolizumab in patients with advanced solid cancers

3区 · 医学

Article

作者: Hardwick, N ; Li, D ; Kos, F J ; Chung, V ; Waisman, J ; Frankel, P ; Li, M ; Chao, J ; Zurcher, K ; Diamond, D J ; Yuan, Y

BACKGROUNDVaccination of cancer patients with p53-expressing modified vaccinia Ankara virus (p53MVA) has shown in our previous studies to activate p53-reactive T cells in peripheral blood but without immediate clinical benefit. We hypothesized that the immunological responses to p53MVA vaccine may require additional immune checkpoint blockade to achieve clinically beneficial levels. We therefore conducted a phase I trial evaluating the combination of p53MVA and pembrolizumab (anti-PD-1) in patients with advanced solid tumors.PATIENTS AND METHODSEleven patients with advanced breast, pancreatic, hepatocellular, or head and neck cancer received up to 3 triweekly vaccines in combination with pembrolizumab given concurrently and thereafter, alone at 3-week intervals until disease progression. The patients were assessed for toxicity and clinical response. Correlative studies analyzed p53-reactive T cells and profile of immune function gene expression.RESULTSWe observed clinical responses in 3/11 patients who remained with stable disease for 30, 32, and 49 weeks. Two of these patients showed increased frequencies and persistence of p53-reactive CD8⁺ T cells and elevation of expression of multiple immune response genes. Borderline or undetectable p53-specific T cell responses in 7/11 patients were related to no immediate clinical benefit. The first study patient had a grade 5 fatal myocarditis. After the study was amended for enhanced cardiac monitoring, no additional cardiac toxicities were noted.CONCLUSIONWe have shown that the combination of p53MVA vaccine with pembrolizumab is feasible, safe, and may offer clinical benefit in select group of patients that should be identified through further studies.

2018-03-15·Clinical Cancer Research1区 · 医学

p53-Reactive T Cells Are Associated with Clinical Benefit in Patients with Platinum-Resistant Epithelial Ovarian Cancer After Treatment with a p53 Vaccine and Gemcitabine Chemotherapy

1区 · 医学

Article

作者: Leong, Lucille ; Cristea, Mihaela ; Kos, Ferdynand ; Eng, Melissa ; Kaltcheva, Teodora ; Tinsley, Raechelle ; Tsai, Weimin ; Frankel, Paul ; Kilpatrick, Julie ; Chung, Vincent ; Diamond, Don J. ; Ellenhorn, Joshua D.I. ; Wilczynski, Sharon ; Ruel, Christopher ; Hardwick, Nicola R. ; Morgan, Robert

AbstractPurpose: To conduct a phase I trial of a Modified Vaccinia Ankara vaccine delivering wild-type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer.Experimental Design: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses.Results: Eleven patients were evaluated for p53MVA/gemcitabine toxicity, clinical outcome, and immunologic response. Toxicity: there were no DLTs, but 3 of 11 patients came off study early due to gemcitabine-attributed adverse events (AE). Minimal AEs were attributed to p53MVA vaccination. Immunologic and clinical response: enhanced in vitro recognition of p53 peptides was detectable after immunization in both the CD4+ and CD8+ T-cell compartments in 5 of 11 and 6 of 11 patients, respectively. Changes in peripheral T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSC) did not correlate significantly with vaccine response or progression-free survival (PFS). Patients with the greatest expansion of p53-reactive T cells had significantly longer PFS than patients with lower p53-reactivity after therapy. Tumor shrinkage or disease stabilization occurred in 4 patients.Conclusions: p53MVA was well tolerated, but gemcitabine without steroid pretreatment was intolerable in some patients. However, elevated p53-reactive CD4+ and CD8+ T-cell responses after therapy correlated with longer PFS. Therefore, if responses to p53MVA can be enhanced with alternative agents, superior clinical responses may be achievable. Clin Cancer Res; 24(6); 1315–25. ©2018 AACR.

100 项与 MVA p53 vaccine (Tara Immuno-Oncology) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
复发性卵巢癌	临床2期	美国	National Cancer Institute	2018-02-01
复发性铂耐药性输卵管癌	临床2期	美国	National Cancer Institute	2018-02-01
复发性铂耐药性卵巢癌	临床2期	美国	National Cancer Institute	2018-02-01
复发性铂耐药性原发性腹膜癌	临床2期	美国	National Cancer Institute	2018-02-01
胰腺癌	临床1期	美国	National Cancer Institute	2011-10-01
直肠癌	临床1期	美国	National Cancer Institute	2011-10-01
复发性原发性腹膜癌	临床前	美国	National Cancer Institute	2015-01-01
复发性结肠癌	临床前	美国	National Cancer Institute	2011-10-01
复发性胃癌	临床前	美国	National Cancer Institute	2011-10-01
III期结肠癌	临床前	美国	National Cancer Institute	2011-10-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03113487 (CTgov)	临床2期	复发性铂耐药性原发性腹膜癌 \| 复发性卵巢癌 \| 复发性铂耐药性输卵管癌 \| 复发性铂耐药性卵巢癌	29	Pembrolizumab+p53MVA	遞製簾淵夢範製構蓋憲(顧鏇壓獵製獵構遞膚淵) = 夢鹽網衊製淵鹹構衊衊鬱衊壓襯構壓範製構構 (鬱醖遞鏇淵艱網艱遞網, 積網鏇築膚夢壓糧鬱壓 ~ 鑰齋廠廠願壓醖衊廠顧) 更多	-	2024-10-08
NCT02432963 (ASCO2018 \| ASCO_SITC2018) 人工标引	临床1期	实体瘤	-	p53MVA vaccine+pembrolizumab (TNBC)	(蓋淵襯憲蓋齋夢築艱蓋) = 鏇積鬱廠願遞積衊鑰鏇齋鬱糧願鬱鏇餘糧製醖 (艱淵糧積築壓蓋構淵網 ) 更多	积极	2018-01-25
NCT02432963 (ASCO2018 \| ASCO_SITC2018) 人工标引	临床1期	实体瘤	-	p53MVA vaccine+pembrolizumab (HNSCC)	(蓋淵襯憲蓋齋夢築艱蓋) = 餘糧製憲壓鏇繭顧壓淵齋鬱糧願鬱鏇餘糧製醖 (艱淵糧積築壓蓋構淵網 )	积极	2018-01-25
NCT02275039 (ASCO 12016 \| ASCO 22016) 人工标引	临床1期	复发性卵巢癌	-	p53MVA vaccine+gemcitabine	(餘範積築製蓋淵衊繭築) = not meeting DLT definition included: neutropenia (grade 3 in 1 pt, grade 4 in 1 pt), anemia (grade 3, 2pts), hyperuricemia (grade 4, 1pt) hyponatremia (grade 3, 1pt), leukopenia (grade 3, 1pt) 觸獵憲觸壓繭餘醖糧襯 (網築夢憲獵廠鑰範膚衊 ) 更多	积极	2016-06-03
ASCO2007	临床2期	卵巢癌	21	Subcutaneous peptide admixed with ISA-51 and GM-CSF adjuvants	觸願蓋淵築願淵襯網艱(顧鏇齋齋廠鑰艱獵壓廠) = 遞鹹壓醖餘願繭製觸蓋膚鹽廠繭觸簾鏇網膚鏇 (艱繭醖襯鹹夢製簾積鑰 ) 更多	-	2007-06-20
ASCO2007	临床2期	卵巢癌	21	p53 vaccine (Peptide-pulsed dendritic cells given intravenously)	觸願蓋淵築願淵襯網艱(顧鏇齋齋廠鑰艱獵壓廠) = 構淵鏇鬱鹽餘顧顧積遞膚鹽廠繭觸簾鏇網膚鏇 (艱繭醖襯鹹夢製簾積鑰 ) 更多	-	2007-06-20