Search results for "immunotherapy"

In the literature: April 2019

2019

Glioblastoma (GBM) remains an unmet need in Medical Oncology considering its poor prognosis and the lack of advances in therapeutics in more than one decade.1 Despite the initial enthusiasm, the development of immunotherapy in GBM has proved to be challenging, with a disappointing negative phase III clinical trial.2 Some of the phenotypic hallmarks of GBM make immunotherapy difficult. Its relatively low mutational load, its immunologically ‘cold’ microenvironment with scarce infiltrating immune effector cells, a dominant myeloid compartment composed by microglia and myeloid-derived suppressor cells and a strong immunosuppression, both local, mediated by immunosuppressive regulatory T cells …

Association of immune-regulatory (FoxP3+)-T-cell tumor infiltration status with benefit from chemoimmunotherapy with gemcitabine, oxaliplatin, 5-FU/F…

2009

3045 Background: GOLFIG is a novel chemoimmunotherapy regimen, combining gemcitabine, oxaliplatin, 5-FU/FA with immunoadjuvant GM-CSF and aldesleukine, which resulted safe and very active in colon cancer patients. Antitumor activity and immunity feedback to the treatment resulted strictly correlated. The best outcome was observed in patients showing autoimmunity signs, rise in central-memory-T cells, and decline in peripheral and tumor infiltrating immuno-regulatory T (Treg) cells. On these bases, we investigated a possible correlation between Treg tumor infiltration at diagnosis and clinical outcome of these patients. Methods: An immunohistochemistry study was carried out to quantify the …

Abstract 4082: Preclinical assessment of external or targeted radiotherapy in combination with immunotherapies and co-development of companion imagin…

2019

Abstract Immunotherapies have proven to be highly efficient for cancer treatments and combination with either internal vectorized or external radiotherapies can enhance this efficacy through notably increasing tumor immune infiltrate. The clinical evaluation of such combination therapies requires expertise and exquisite processes in multiple fields, immunotherapy, radiotherapy and nuclear medicine. Similarly, this applies into preclinical settings for assessing proof of concept of novel combinations. Herein, we will present our preclinical evaluation process to combine external or internal (i.e. lutetium-177 radiolabeled molecule) radiotherapy with immunotherapies that include radiochemistr…

Abstract CT201: The Mutanome Engineered RNA Immuno-Therapy (MERIT) project

2015

Abstract The Mutanome Engineered RNA Immuno-Therapy (MERIT) consortium will clinically and industrially validate a pioneering RNA-based immunotherapy concept that targets individual tumor antigens and tumor-specific mutations in triple negative breast cancer (TNBC) patients. This biomarker-guided, personalized therapy is a collaborative effort of five partners from academia and industry and is funded by the European Commission's FP7 and led by BioNTech AG. TNBC is an aggressive, molecularly heterogeneous cancer that accounts for 20% of all breast cancer patients. The 5-year survival rate is less than 80%. The molecular heterogeneity across TNBCs results in a lack of common targetable molecu…

Sequential ipilimumab (Ipi) versus best supportive care (BSC) following first-line chemotherapy (Ctx) in patients (pts) with unresectable locally adv…

2013

TPS4151 Background: First-line systemic CTX is standard-of-care for advanced gastric cancer. However, most pts relapse or have severe adverse events (AEs), creating a need for new therapies with better benefit/risk and toxicity profiles. Endogenous immune activity against tumor cells has been demonstrated in the human gastric cancer tumor microenvironment, supporting a role for immunotherapy. As a new maintenance concept, sequential administration of immunotherapy may prolong clinical benefit of first-line CTX before disease progression (PD). Ipi, a fully human monoclonal antibody which binds CTLA-4, augments the antitumor immune response. Ipi improved overall survival (OS) in patients wit…

Progression-Free Survival Early Assessment Is a Robust Surrogate Endpoint of Overall Survival in Immunotherapy Trials of Hepatocellular Carcinoma

2020

Background: Radiology-based outcomes, such as progression-free survival (PFS) and objective response rate (ORR), are used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of PFS with overall survival (OS) in clinical trials of systemic therapies targeting advanced hepatocellular carcinoma (HCC) by novel meta-regression methods. Methods: A search of databases (PubMed, American Society of Clinical Oncology (ASCO), and European Society for Medical Oncology (ESMO) Meeting Libraries, Clinicaltrials.gov) for trials of systemic therapies for advanced HCC reporting both OS and PFS was performed. Individual patient data were extracted from PFS and OS Kaplan&nd…

Understanding mechanisms of primary resistance to checkpoint inhibitors will lead to precision immunotherapy of advanced gastric cancer

2019

Systemic Inflammatory Markers and Oncologic Outcomes in Patients with High-risk Non-muscle-invasive Urothelial Bladder Cancer

2018

Background: Serum levels of neutrophils, platelets, and lymphocytes have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer (BC). Objective: To evaluate the prognostic role of the combination of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) in patients with high-risk non–muscle-invasive urothelial BC (NIMBC). Design, setting, and participants: A total of 1151 NMIBC patients who underwent first transurethral resection of the bladder tumor (TURBT) at 13 academic institutions between January 1, 2002 and December 31, 2012 were included in this analysis. The median follow-up was 48 mo.…

Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX ch…

2013

The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/ label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m 2, day 1); oxaliplatin (85 mg/m2, day 2); levofolinate (100 mg/m2, days 1-2), 5-fluorouracil (5-FU) (400…

Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy

2016

Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median C(max) and C(trough) values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher C(max) and C(trough) values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas …