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  • 1
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    A phase 2, open-label study of rucaparib in patients with pancreatic cancer and a known deleterious BRCA mutation.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. TPS4161-TPS4161
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. TPS4161-TPS4161
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.tps4161
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Development of artificial intelligence–derived histological biomarkers for first-line treatment selection in metastatic pancreatic ductal adenocarcinoma (mPDAC).
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 743-743
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 743-743
    Abstract: 743 Background: The prognosis of metastatic pancreatic ductal adenocarcinoma (mPDAC) remains poor with a median survival time of 10-12 months. First-line treatment is largely influenced by performance status with fit patients more often receiving FOLFIRINOX (FFX) than Gemcitabine+Nab-Paclitaxel (GNP). Although the two regimens have improved outcomes over gemcitabine monotherapy, no biomarkers routinely used in clinical practice can predict which regimen is optimal to facilitate a precision medicine approach. We developed two signatures (V-FFX and V-GNP) associated with treatment outcomes for the respective first-line regimens using a retrospective cohort of mPDAC cases. Methods: We conducted a retrospective study of mPDAC patients treated at two institutions (UPMC and Cedars Sinai) from 2014 to 2021. Digitized histological H & E sections corresponding to 145 metastatic PDAC patients treated with either first-line FFX or GNP were included. Independent randomized training and test datasets were constructed for FFX-treated (train: 41, test: 25) and GNP-treated (train: 49, test: 30) patients. To construct the histological assay, a deep-learning algorithm then segmented nuclei to extract quantitative histological features. Features associated with disease-specific survival (DSS) for FFX and GNP were identified utilizing univariate Cox proportional hazards (CPH) models for the respective training sets and V-FFX and V-GNP signatures were constructed. DSS stratification of the V-FFX and V-GNP signatures were examined using Kaplan-Meier analysis and the log-rank test and DSS percentages at 12 months were calculated on the respective test sets. Results: The V-FFX and V-GNP signatures were found to be significantly associated with treatment outcomes stratified in the respective test sets (log-rank test, V-FFX: p=0.046, V-GNP: p=0.004). 29 of 55 patients tested positive for only one of either V-FFX and V-GNP signatures. Kaplan-Meier analysis demonstrated robust separation with hazard ratios for the V-FFX and V-GNP signatures of 3.01 (95% CI: 0.96, 9.45) and 4.81 (95% CI: 1.74, 13.3). DSS at 12 months for patients in V-FFX +ve vs -ve groups were 88% (8/9) vs 50% (7/14). DSS at 12 months for patients in V-GNP +ve vs -ve groups were 66% (8/12) vs 15% (2/13). Conclusions: AI derived V-FFX and V-GNP morphological signatures were strongly associated with treatment outcomes for first-line FFX and GNP and can potentially aid in the selection of first-line treatment for mPDAC patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.743
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 3
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    Gemcitabine response prediction in the adjuvant treatment of resected pancreatic ductal adenocarcinoma using an AI histopathology platform.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e16295-e16295
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16295-e16295
    Abstract: e16295 Background: Adjuvant chemotherapy improves survival following resection of pancreatic ductal adenocarcinoma (PDAC). A modified fluorouracil/irinotecan/oxaliplatin regimen (mFOLFIRINOX) has demonstrated improved disease free survival and overall survival, though gemcitabine-based monotherapy and gemcitabine plus capecitabine are alternatives in less fit patients. Though there are several proposed biomarkers to guide treatment decisions (GATA6, hENT1, and GemPred), no biomarker is used to guide treatment selection in clinical practice. Consequently, we sought to develop an artificial intelligence-derived signature of features from digital images of routine histopathology specimens that could identify patients susceptible to routine chemotherapeutic agents. Methods: 139 whole-slide digitized histological slides corresponding to 102 resected PDAC tumors from TCGA-PAAD were used in this study. This dataset corresponded to patients that had received either gemcitabine-backbone or 5 FU-backbone chemotherapy as their first-line adjuvant treatment. We extracted nuclei images from tissue regions using segmentation models and computed geometric features of these nuclei which we then correlated with Disease Specific Survival (DSS) in order to construct a signature associated with treatment benefit. This signature was compared against two board certified pathologists using the grade of the digital slides images to classify patients into above or below average DSS buckets. Results: Among quantitative geometric features, a set of area and ellipse features describing nuclei geometry correlated most with response to gemcitabine (R̃0.4). The cox proportional hazards model using these geometric nuclei features was found to be predictive of response to gemcitabine and achieved a C-index (95% CI) of 0.69 (0.58, 0.79). The pathologist-based baseline model for above and below average DSS had a median DSS of 443 and 461 days respectively. Using the average expected lifetime as the threshold, the model divides patients receiving gemcitabine into two histological subtypes with median DSS of 586 and 394 days respectively (p 〈 0.05). The model appeared specific to gemcitabine. Among patients receiving 5-FU (n = 10) there was no statistical significance in median DSS between the subtypes and a c-index of 0.63 (0.27, 1.0). Conclusions: An artificial intelligence approach utilizing only routine histopathology can identify features that correlate with treatment outcomes in PDAC with classification performance (c-index:0.69) superior to the validated AJCC treatment prediction tool (0.59).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e16295
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Phase II study of PEGPH20 plus pembrolizumab for patients (pts) with hyaluronan (HA)-high refractory metastatic pancreatic adenocarcinoma (mPC): PCRT16-001.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 4_suppl ( 2022-02-01), p. 576-576
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 4_suppl ( 2022-02-01), p. 576-576
    Abstract: 576 Background: Stromal HA poses a physical barrier and protects tumor cells from immune surveillance. PEGPH20 is a pegylated, human recombinant PH20 hyaluronidase that remodels tumor stroma. Preclinical studies of PEGPH20 showed improved infiltration of cytotoxic T-lymphocytes and delivery of chemotherapy and PD1/PD-L1 antibodies. This study aimed to evaluate the efficacy, safety, and translational biomarkers of PEGPH20 plus pembrolizumab in pts with HA-high refractory mPC. Methods: mPC pts with HA-high expression, ECOG PS 0-1, ≤ 2 prior therapies for metastatic disease, life expectancy ≥ 12 weeks were treated with PEGPH20 3 µg/kg iv on D1, D8, D15 and pembrolizumab 200 mg iv on D1 in 21-day cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints were safety, overall survival (OS), and objective response rate (ORR). Blood and tumor biopsies were collected at baseline and on-study. Translational endpoints included flow cytometry and IHC for immune subsets, T-cell receptor sequencing, immune transcriptome, circulating cytokines, and plasma and tumor HA levels. Assuming a one-sided α-level of 0.05 and power of 80%, 31 evaluable pts were needed to detect an improvement of median PFS from 3 to 6 months. Results: Between May 2019 to Nov 2019, 38 pts were screened for HA expression, and 8 pts were enrolled, with median age 68 years (range 60-73), 7 males, and median 2 prior therapies (range 1-4). The accrual was stopped early by Halozyme Pharmaceuticals due to lack of benefit from PEGPH20 added to chemotherapy in the HALO-301 study. Treatment exposure median was 2 cycles (range 1-6). Reasons for study discontinuation were disease progression (n = 4), termination by sponsor (n = 3), patient withdrawal to enroll in hospice (n = 1). Treatment related toxicities were musculoskeletal (n = 6, grade 1/2), edema (n = 2, grade 1), fatigue (n = 1, grade 3), dyspnea (n = 1, grade 2), hypothyroidism (n = 1, grade 2). Median OS was 7.2 months (95% CI 1.2-11.8), and median PFS was 1.5 months (95% CI 0.9-4.4). Best response was stable disease (n = 2, 25%) lasting 2.2 and 9 months, respectively, and no responses were noted. Patients with available molecular sequencing data had MSS tumors. Translational biomarkers will be presented. Conclusions: Pembrolizumab and PEGPH20 did not increase PFS compared to historical data among heavily pretreated mPC pts, but the median OS of 7.2 months is encouraging. Translational analyses will provide insights into immune modulatory effects from PEGPH20 that could inform future studies with stroma targeted therapies and immune checkpoint blockade in mPC. Clinical trial information: NCT03634332.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.4_suppl.576
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Phase III double-blinded, placebo-controlled study of MABp1 for improving survival in metastatic colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 4_suppl ( 2016-02-01), p. TPS784-TPS784
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. TPS784-TPS784
    Abstract: TPS784 Background: Interleukin 1 alpha (IL-1a) is a pro-inflammatory cytokine that initiates and propagates sterile inflammatory responses. IL-1a is present on the surface of tumors, and released from necrotic cells within the microenvironment, where it upregulates MMPs, VEGF, chemotactic cytokines, and IL-6 contributing to tumor growth and infiltration of the microenvironment by T-regulatory cells and tumor associated macrophages. IL-1a is also found on the surface of platelets and activates vascular endothelium allowing for circulating tumor cells to establish new areas of metastasis. Specific blockade of IL-1a with the true human IgG1k antibody MABp1, is expected to deprive the tumor of its ability to grow, spread, and evade immune surveillance. A phase I/II study showed radiographic evidence of tumor response in mCRC patients, as well as clinically meaningful improvement in cancer associated symptoms, with no significant toxicity. In the context of this therapy, the improvement in key cancer symptoms, including reversal of lean body mass loss, fatigue, and anorexia, is the direct result of an anti-neoplastic effect and is expected to correlate with an overall survival benefit. Methods: This “Phase III Study of MABp1 in Patients With Advanced Colorectal Cancer (XCITE)” is a global study of 600 patients, ECOG-PS 0-2, metastatic CRC refractory to oxaliplatin, irinotecan, fluoropyrimidine, and EGFR-inhibitors if KRAS wildtype. Patients are randomized 2:1 to receive MABp1 7.5 mg/kg iv every two weeks plus best supportive care (BSC) versus placebo (iv Q2 week) plus BSC. BSC does not include any other therapy with proven anti-cancer activity. The primary endpoint is OS, with secondary endpoints of PFS, ORR, change in lean body mass, and QoL. Patients continue on trial until clinical or radiographic progression as defined by the immune related response criteria (irRC). The study is powered to show a clinically meaningful improvement in OS, evaluated by log-rank test with a one-sided alpha of 0.025. As of September 2015, enrollment is currently underway in the United States and Europe, and results of the first interim analysis are expected in 2016. [NCT01767857]. Clinical trial information: NCT01767857.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.4_suppl.tps784
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Online Resource
    Demoralization and depression in pancreatic cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 4_suppl ( 2020-02-01), p. TPS778-TPS778
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. TPS778-TPS778
    Abstract: TPS778 Background: Demoralization is a maladaptive coping response to stressful situations characterized by thoughts of hopelessness, helplessness, and loss of meaning and purpose. Psychometrically, it is measured using the Demoralization-Scale II (DS-II), a validated questionnaire that yields a patient-reported quantification (scale 0-32) of demoralization. Previous studies involving patients with progressive disease have uncovered a strong positive correlation between demoralization and depression, respectively measured by the DS-II and Patient Health Questionnaire-9 (PHQ-9) surveys. Here, we aim to characterize demoralization and its relationship to depression in pancreatic cancer patients, a unique patient population in terms of its poor prognosis. We hypothesize that demoralization is highly prevalent in the pancreatic cancer patient population and strongly correlated with depression. Methods: Eligible patients with an active pancreatic cancer diagnosis, after consenting to an IRB approved protocol, will be administered the DS-II and PHQ-9 surveys to yield psychometric measurements for analysis. The primary objective of this project is to determine the association between demoralization (DS-II) and depression (PHQ-9) in pancreatic cancer patients. Secondary objectives include associations between demoralization and ethnicity, sexual orientation, suicidal ideation, education, cancer stage, and disease progression. Data will be analyzed via simple linear regression. An ANOVA will also be conducted using DS-II groups as the categorical variable and PHQ-9 scores as the continuous variable, and vice versa. This is a multi-institutional study to be conducted at Cedars-Sinai Medical Center, New York University, University of Washington, UC San Francisco, and Lewis Katz Schools of Medicine.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.4_suppl.TPS778
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Leveraging patient-reported outcomes (PROs) in patients with pancreatic cancer: The Pancreatic Cancer Action Network (PanCAN) online patient registry experience.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 29_suppl ( 2020-10-10), p. 154-154
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 29_suppl ( 2020-10-10), p. 154-154
    Abstract: 154 Background: By allowing patients (pts) to self-report key issues related to their quality of life and symptoms, PROs have important clinical and research implications. The PanCAN Registry, which began collecting data in July 2015, is a pancreatic cancer-specific global online registry enabling pts to report sociodemographics, disease/management characteristics, and PROs via online surveys. We sought to describe pt experiences with the PanCAN Registry. Methods: We assessed individual characteristics and interactions with the registry (visits, survey completions, and longitudinal use) from 7/2015-10/2019 for pts who provided permission to use their data. The registry allows pts to complete surveys about their experience (e.g. basics of pancreatic cancer, general information), symptoms (e.g. fatigue, pain), diagnostics (e.g. labs, scans), and drug therapy (e.g. type, frequency). We validated PROs using the PanCAN Know Your Tumor database. For a subset of pts (those with de novo metastatic disease), we compared PROs, treatment patterns, and side effects by age (+/- 65 years) and treatment site (community or academic). Results: Of 2,836 pts who visited the registry, 2,076 (73%) completed at least one survey (median age = 64 [range: 18-97], 48% women, 92% white, 32% metastatic disease). Pts most commonly completed the basics (73%), general information (39%), and drug therapy (37%) surveys. Overall, 10% answered surveys longitudinally. We observed 95% concordance between PROs and the PanCAN Know Your Tumor database. Among the 667 pts with de novo metastatic disease, 34% were older (age 65+) and 50% were treated at academic sites. Younger pts were more hopeful about the treatment plan (strongly agree: 24% v 12%, p 〈 .01) and reported less constipation (moderate/severe: 33% v 48%, p 〈 .01) compared with older pts. Pts treated at academic sites reported less frequent treatment breaks of 〉 2 weeks (28% v 58%, p = 0.01) and more frequent severe cytopenias (27% v 12%, p = 0.01) compared with those treated at community sites. Conclusions: With 〉 2,800 pts visiting the PanCAN registry and 〉 70% completing a survey, these findings demonstrate the feasibility, robustness, and research potential of an online PRO registry. We observed important differences by age and treatment site regarding pts’ outlook, symptoms, treatment patterns, and side effects. With increasing focus on PROs, registries like this can facilitate standardized PRO reporting and monitoring, while also providing a valuable research database.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.29_suppl.154
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 8
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    Precision Promise (PrP): An adaptive, multi-arm registration trial in metastatic pancreatic ductal adenocarcinoma (PDAC).
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS4188-TPS4188
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS4188-TPS4188
    Abstract: TPS4188 Background: The success rate of drug development in PDAC is disappointingly low.PrP is a transformative, adaptive platform clinical trial designed to continuously evaluate many novel therapeutic options while increasing the probability that patients (pts) are randomized to effective experimental therapies. It cultivates enhanced cooperation among groups representing pts advocacy, pharmaceutical companies, academia, and the FDA. This patient-centric study aims to become the largest Phase 3 registrational study in PDAC and represents a fundamental shift in drug development for PDAC in the United States (US). Methods: PrP (NCT04229004) is a platform clinical trial sponsored by the Pancreatic Cancer Action Network (PanCAN), developed based on the FDA 2020 guidance document regarding "complex innovative designs" in registration trials https://www.fda.gov/media/130897/download . It utilizes adaptive randomization and other Bayesian statistical innovations provided by Berry Consultants LLC, including the “time machine” which uses all previously randomized controls for each arm, suitably adjusted for line of therapy and the time period of the arm. Focused on 1 st and 2 nd line treatment of mPDAC, PrP uses an adaptive platform design with randomization to one of 2 control arms (gemcitabine + nab-paclitaxel (GA) or mFOLFIRINOX, 30% of pts) or experimental therapy (70% of pts). Candidate experimental arms are reviewed by an Arm Selection Committee based on validity of the treatment target and strength of the pre-clinical and clinical data. The primary endpoint is overall survival (OS). Pts undergo pre- and on-treatment biopsies with state-of-the-art genomic, transcriptomic, and immune analysis, along with a serial collection of blood-based research samples. Pts are managed using novel supportive care techniques; PrP contains 3 sub-protocols evaluating quality of life, sarcopenia, and actigraphy. PrP launched in 2020 and has enrolled 〉 130 pts; 30 US sites have been selected with 17 currently active. Current experimental arms include: (i) GA + Pamrevlumab, an anti-CTGF Ab, (ii) Racemetyrosine monotherapy, a cancer metabolism-based therapy (for follow-up of patients) and (iii) an immuno-oncology arm in activation. Other arms are in the planning stages. Compared to traditional designs, PrP offers several advantages: multiple investigational treatments evaluated in parallel over time; ̃175 pts per experimental arm required to initiate a regulatory registration; and continuous learning from every patient, resulting in significant savings of time and resources. PrP has created an entirely new learning environment for accelerating drug development in PDAC. Clinical trial information: NCT04229004.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.TPS4188
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 9
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    RUCAPANC: An open-label, phase 2 trial of the PARP inhibitor rucaparib in patients (pts) with pancreatic cancer (PC) and a known deleterious germline or somatic BRCA mutation.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 4110-4110
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 4110-4110
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.4110
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 10
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    PCRT16-001: Phase II study of PEGPH20 plus pembrolizumab for patients (pts) with hyaluronan (HA)-high refractory metastatic pancreatic ductal adenocarcinoma (mPDA).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 4_suppl ( 2020-02-01), p. TPS785-TPS785
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. TPS785-TPS785
    Abstract: TPS785 Background: PDA is characterized by invasiveness and therapeutic resistance in part due to a desmoplastic stroma and an immunosuppressive microenvironment ( Provenzano PP, Hingorani S. Br J Cancer 2013). PD1/PD-L1 inhibitors have no single agent activity in PDA, except for pts with mismatch repair defects. There is high need to overcome resistance to immune targeted therapies and develop biomarkers for pts selection. Stromal HA poses a physical barrier and protects tumor cells from immune surveillance ( Kultti A, et al Biomed Res Int 2014). By remodeling the tumor stroma, PEGPH20 allows infiltration of cytotoxic T lymphocytes, and improves delivery of chemotherapy and PD1/PD-L1 antibodies ( Singha NC, et al Mol Cancer Ther 2015). mPDA pts refractory to 1 st line therapy have median overall survival (OS) of 6 mos. We hypothesize that stroma remodeling with PEGPH20 sensitizes PDA to immune therapy, and stroma and immunologic biomarkers will identify pts most likely to benefit. In this trial we will evaluate the efficacy, safety and translational biomarkers of PEGPH20 plus pembrolizumab in HA-high refractory mPDA. Methods: Eligible pts have ECOG PS 0-1, ≤ 2 prior therapies for mPDA, life expectancy ≥ 12 wks, able/willing to have tumor biopsies at baseline and after 6 wks of treatment. PEGPH20 dosing is 3 µg/kg iv QW and pembrolizumab 200 mg iv Q3W (2-4 hrs after PEGPH20 on wk 1) in 3-wk cycles. All pts receive prophylactic low molecular weight heparin. Primary endpoint: progression-free survival (PFS). Secondary endpoints: safety, OS, response rates. Translational endpoints: flow cytometry of peripheral and intratumoral immune cells, T-cell receptor sequencing, immune transcriptome, immune subsets IHC, circulating cytokines, serial plasma and tumor HA levels. For the primary endpoint of PFS, with a sample size of 31 evaluable pts, a one-sided α-level of 0.05, assuming 12 mos of accrual and 6 mos of follow-up, this study has 80% power to detect a difference between the null hypothesis median PFS 3 mos, versus the alternative hypothesis median PFS 6 mos. The study was activated in May 2019 and is open to accrual; 6 pts were enrolled as of 24Sept 2019. Clinical trial information: NCT03634332.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.4_suppl.TPS785
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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