scholarly journals A Neoantigen-Based Peptide Vaccine for Patients With Advanced Pancreatic Cancer Refractory to Standard Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Zheling Chen ◽  
Shanshan Zhang ◽  
Ning Han ◽  
Jiahong Jiang ◽  
Yunyun Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Cancer Patients ◽  
Peptide Vaccine ◽  
Advanced Pancreatic Cancer ◽  
Effector Memory ◽  
Post Vaccination ◽  
Specific Subset ◽  
Vaccine Treatment

BackgroundNeoantigens are critical targets to elicit robust antitumor T-cell responses. Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients’ overall survival (OS) for several cancer types. However, the safety and efficacy of these vaccine modalities remains unclear in pancreatic cancer patients.MethodsThis retrospective study enrolled 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by our in-house pipeline iNeo-Suite were selected, manufactured and administered to these patients with low tumor mutation burden (TMB) (less than 10 mutations/Mb). Each patient received multiple doses of vaccine depending on the progression of the disease. Peripheral blood samples of each patient were collected pre- and post-vaccination for the analysis of the immunogenicity of iNeo-Vac-P01 through ELISpot assay and flow cytometry.ResultsNo severe vaccine-related adverse effects were witnessed in patients enrolled in this study. The mean OS, OS associated with vaccine treatment and progression free survival (PFS) were reported to be 24.1, 8.3 and 3.1 months, respectively. Higher peripheral IFN-γ titer and CD4+ or CD8+ effector memory T cells count post vaccination were found in patients with relatively long overall survival. Remarkably, for patient P01 who had a 21-month OS associated with vaccine treatment, the abundance of antigen-specific TCR clone drastically increased from 0% to nearly 100%, indicating the potential of iNeo-Vac-P01 in inducing the activation of a specific subset of T cells to kill cancer cells.ConclusionsNeoantigen identification and selection were successfully applied to advanced pancreatic cancer patients with low TMB. As one of the earliest studies that addressed an issue in treating pancreatic cancer with personalized vaccines, it has been demonstrated that iNeo-Vac-P01, a personalized neoantigen-based peptide vaccine, could improve the currently limited clinical efficacy of pancreatic cancer.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT03645148).Registered August 24, 2018 - Retrospectively registered

scholarly journals Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multi-centre, parallel group, double-blind, randomised controlled clinical trial (MISTRAL)

2020 ◽  
Author(s):  
Kathrin Wode ◽  
Johanna Hök Nordberg ◽  
Gunver Sophia Kienle ◽  
Nils Elander ◽  
Britt-Marie Bernhardson ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Advanced Pancreatic Cancer ◽  
Health Related Quality ◽  
Mistletoe Extract ◽  
Related Quality ◽  
Health Related

Abstract Background Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported. The objective of the present study is to assess the value of mistletoe extract as a complement to standard 18 treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with 19 regard to overall survival and health-related quality of life. Methods The trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01mg to 20mg three times per week for nine months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status zero to two; main exclusion criteria are life expectancy less than four weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews. Discussion To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer. Trial registration EU Clinical Trial Register, EudraCT Number 2014-004552-64. Registered 19 January 2016, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004552-64/SE

A phase II study of lapatinib and capecitabine in first-line treatment of metastatic pancreatic cancer (ICORG 08- 39).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 315-315 ◽  
Author(s):  
R. S. McDermott ◽  
P. Calvert ◽  
M. Parker ◽  
G. Webb ◽  
B. Moulton ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Survival Duration ◽  
Synergistic Activity ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

315 Background: The combination of capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer patients has proved beneficial in terms of median survival duration, objective radiological response rate and decrease in tumour marker levels from baseline. In the phase I study of capecitabine and lapatinib carried out in advanced solid tumors, the optimal tolerated regimen was determined to be lapatinib 1,250 mg plus capecitabine 2,000 mg/m2/day. At these dose levels, the combination was well tolerated with few grade 3 toxicities and no grade 4 toxicity. Our preclinical work suggested synergistic activity of capecitabine and lapatinib in pancreatic cancer. We initiated a study of this combination in the first-line therapy of metastatic pancreas cancer. Methods: This was a single-arm multicenter study in patients with chemotherapy-naive metastatic pancreatic cancer. The primary endpoint was overall survival. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 12 patients. If at least seven of these patients survived for at least six months, then a further 20 patients would be enrolled into the study. If six or fewer of the initial 12 patients met the specified study survival criteria, the study would be halted. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Clinical and laboratory parameters were assessed to evaluate disease response and toxicity of therapy. The study patients received lapatinib 1,250 mg/day, plus capecitabine 2000 mg/m2/day on days 1-14 every 21 days. Results: Nine patients were enrolled. Seven of these patients did not achieve the interim protocol response requirement of survival for at least 6 months, to allow for the study to continue to the second cohort of patients. Median overall survival from first dose was 4 months. Median time on treatment was 2 months. There were no objective responses. There were no unexpected toxicities. Conclusions: The addition of lapatinib to capecitabine does not improve overall survival in the first-line treatment of advanced pancreatic cancer patients. [Table: see text]

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors for locally advanced pancreatic cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 326-326
Author(s):  
Byung Min Lee ◽  
Seung Yeun Chung ◽  
Jee Suk Chang ◽  
Kyong Joo Lee ◽  
Si Young Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Pre Treatment

326 Background: It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and in combination would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. Methods: A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR < 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR < 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Results: Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR < 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR < 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR < 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p = 0.011) and PFS (p = 0.026). PLR > 149 also proved to be a significant factor for poorer OS (p = 0.003) and PFS (p = 0.021). Conclusions: Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. Pre-treatment NLR and PLR are useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.

scholarly journals Five advanced pancreatic cancer patients in a Phase I study of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (BATS)

2015 ◽  
Vol 3 (Suppl 2) ◽  
pp. P55 ◽  
Author(s):  
Lawrence G Lum ◽  
Minsig Choi ◽  
Archana Thakur ◽  
Abhinav Deol ◽  
Kristie Fields ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Phase I ◽  
Cancer Patients ◽  
Phase I Study ◽  
Bispecific Antibody ◽  
Advanced Pancreatic Cancer ◽  
Activated T Cells

scholarly journals Neoadjuvant Treatment in Locally Advanced Pancreatic Cancer (LAPC) Patients with FOLFIRINOX or Gemcitabine NabPaclitaxel: A Single-Center Experience and a Literature Review

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 981 ◽  
Author(s):  
Fabiana Napolitano ◽  
Luigi Formisano ◽  
Alessandro Giardino ◽  
Roberto Girelli ◽  
Alberto Servetto ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Disease Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Single Center Experience ◽  
Number Of Patients

The optimal therapeutic strategy for locally advanced pancreatic cancer patients (LAPC) has not yet been established. Our aim is to evaluate how surgery after neoadjuvant treatment with either FOLFIRINOX (FFN) or Gemcitabine-NabPaclitaxel (GemNab) affects the clinical outcome in these patients. LAPC patients treated at our institution were retrospectively analysed to reach this goal. The group characteristics were similar: 35 patients were treated with the FOLFIRINOX regimen and 21 patients with Gemcitabine Nab-Paclitaxel. The number of patients undergoing surgery was 14 in the FFN group (40%) and six in the GemNab group (28.6%). The median Disease-Free Survival (DFS) was 77.10 weeks in the FFN group and 58.65 weeks in the Gem Nab group (p = 0.625), while the median PFS in the unresected group was 49.4 weeks in the FFN group and 30.9 in the GemNab group (p = 0.0029, 95% CI 0.138–0.862, HR 0.345). The overall survival (OS) in the resected population needs a longer follow up to be completely assessed, while the median overall survival (mOS) in the FFN group was 72.10 weeks and 53.30 weeks for the GemNab group (p = 0.06) in the unresected population. Surgery is a valuable option for LAPC patients and it is able to induce a relevant survival advantage. FOLFIRINOX and Gem-NabPaclitaxel should be offered as first options to pancreatic cancer patients in the locally advanced setting.

Clinical Roles of Increased Populations of Foxp3+CD4+ T Cells in Peripheral Blood from Advanced Pancreatic Cancer Patients

Pancreas ◽  
2006 ◽  
Vol 33 (4) ◽  
pp. 386-390 ◽  
Author(s):  
Tetsuya Ikemoto ◽  
Takeshi Yamaguchi ◽  
Yuji Morine ◽  
Satoru Imura ◽  
Yuji Soejima ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Advanced Pancreatic Cancer
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