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  • 1
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    A phase I/II clinical trial of autologous CMV-specific T cells in glioblastoma (GBM) patients to reveal a lack of immune effector function.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 2515-2515
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 2515-2515
    Abstract: 2515 Background: Cytomegalovirus (CMV) antigens are present in 〉 90% of GBMs but not in normal brain making it an attractive immunological target. Methods: Highly functional autologous polyclonal CMV pp65 specific T cells were expanded under GMP-compliant conditions from GBM patients and administered after 3 weeks of lymphodepleting dose-dense temozolomide (ddTMZ, 100 mg/m 2 ). The phase I component used a 3+3 design ascending through four dose levels (5 x 10 6 cells to 1 x 10 8 cells). Treatment was repeated every 6 weeks for a total of 4 cycles. Dose expansion was conducted in recurrent GBM patients undergoing resection and in newly diagnosed GBM patients following concurrent chemoradiation. In vivo persistence and effector function of the adoptively transferred CMV-specific T cells was determined by dextramer staining and multiparameter flow cytometry in serially-sampled peripheral blood and in the tumor microenvironment. Results: 65 patients were screened, 25 underwent leukapheresis, and 20 completed at least 1 cycle. Median age 48 (27-69), 35% were MGMT methylated, and 10% were IDH mutated. No dose limiting toxicities (DLTs) observed. Complete radiographic response was observed in 1 patient, partial responses in 2, stable disease in 9, and progressive disease in 8. The median PFS time was 1.3 months (95% CI: 0-8.3 months) and the median OS time was 12 months (95% CI: 6 months to not reached). Repeated infusions of CMV-TC were associated with significant increase in circulating CMV+ CD8+ T cells, but cytokine production reflective of effector activity (CD107a, TNFα, IFNγ, IL2) was suppressed in these cells including directly from the GBM microenvironment. Conclusions: Adoptive infusion of CMV-specific T cells after lymphodepleting ddTMZ was well-tolerated. However, effector function of the adoptively transferred T cells was attenuated indicating further modulation of the T cell is required to prevent its dysfunction prior to proceeding to large scale clinical studies. Clinical trial information: NCT02661282 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.2515
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 2
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    Precision medicine in recurrent glioblastoma: A feasibility trial conducted by the Ivy Foundation Early Phase Clinical Trials Consortium.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. 2031-2031
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 2031-2031
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.2031
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
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  • 3
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    Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 12 ( 2017-04-20), p. 1341-1367
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 12 ( 2017-04-20), p. 1341-1367
    Abstract: I am pleased to present Clinical Cancer Advances 2017, which highlights the most promising advances in patient-oriented cancer research over the past year. The report gives us an opportunity to reflect on what an exciting time it is for cancer research and how swiftly our understanding of cancer has improved. One year ago, the White House announced the national Cancer Moonshot program to accelerate progress against cancer. This shared vision of progress has reinvigorated the research community, identified new areas of scientific collaboration, and raised our ambitions regarding what may be possible beyond the progress we have already made. When I entered the field 35 years ago, I could not have imagined where we would be today. We can now detect cancer earlier, target treatments more effectively, and manage adverse effects more effectively to enable patients to live better, more fulfilling lives. Today, two of three people with cancer live at least 5 years after diagnosis, up from roughly one of two in the 1970s. This progress has resulted from decades of incremental advances that have collectively expanded our understanding of the molecular underpinnings of cancer. There is no better current example of this than ASCO’s 2017 Advance of the Year: Immunotherapy 2.0. Over the last year, there has been a wave of new successes with immunotherapy. Research has proven this approach can be effective against a wide range of hard-to-treat advanced cancers previously considered intractable. Researchers are now working to identify biologic markers that can help increase the effectiveness of treatment and determine who is most likely to benefit from immunotherapy. This knowledge will enable oncologists to make evidence-based decisions so as many patients as possible might benefit from this new type of treatment. Each successive advance builds on the previous hard work of generations of basic, translational, and clinical cancer researchers. Importantly, the advances described in this report would not have been possible without the individuals who volunteered to participate in clinical trials as part of their treatment. To turn the promising vision of a cancer moonshot into meaningful advances, we need sustained, robust federal funding for continued research and innovation. Approximately 30% of the research highlighted in this report was funded, at least in part, through federal dollars appropriated to the National Institutes of Health or the National Cancer Institute. Without this federal investment—unique internationally in scale, duration, and impact for decades—I fear we may lose the forward momentum needed to further the progress we see highlighted in this report. Federal lawmakers can further fuel progress by advancing initiatives that facilitate the use of big data to achieve the common good of high-quality care for all patients. Such programs, like ASCO’s CancerLinQ, will rapidly increase the pace of progress and dramatically expand the reach of treatment advances to the millions of patients who are living with cancer today or who will do so in the future. This investment will yield medical, scientific, economic, and societal benefits for years to come. Much work still lies ahead. Many questions remain about how cancer develops and spreads and how best to treat it. As you read through Clinical Cancer Advances 2017, I hope you are as inspired as I am by the gains the clinical cancer research community has made over the past year and by the promise of a new era of advances just over the horizon. Daniel F Hayes, MD, FASCO, FACP ASCO President, 2016 to 2017
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.71.5292
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 4
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    Paxalisib in patients with newly diagnosed glioblastoma with unmethylated MGMT promoter status: Final phase 2 study results.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 2047-2047
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 2047-2047
    Abstract: 2047 Background: Paxalisib, a potent oral selective brain-penetrant small molecule PI3K/mTOR inhibitor, has shown activity in nonclinical brain cancer models and promising phase 1 data in progressive / recurrent high-grade gliomas (NCT01547546). This multicenter phase 2 progressive design trial (NCT03522298) aimed to establish the maximum tolerated dose (MTD) for once-daily (QD) dosing, and to evaluate safety, tolerability, pharmacokinetics (PK), and clinical activity of paxalisib in patients with newly diagnosed glioblastoma and unmethylated MGMT promotor status. Methods: Eligible patients were males or females, aged ≥18 years, who had undergone surgical resection and chemoradiotherapy (Stupp Regimen), and were considered to be progression free before starting adjuvant paxalisib. Stage 1 used a standard 3+3 dose-escalation design to determine the MTD in this population. Stage 2 was a two-arm, open-label, expansion cohort with patients randomized 1:1 to receive paxalisib at the MTD under fed or fasted conditions. In both stages, treatment comprised daily paxalisib administered in 28-day cycles, continuously until disease progression or unacceptable toxicity. Efficacy analyses are based on investigator review and from date of diagnosis. Results: Patients (n = 30; 70.0% males, 83.3% white, mean age 58.5 years) had a mean time since diagnosis of 3.75 months. The majority (n = 29) received between 1 and 6 treatment cycles and one received 29 cycles. In Stage 1 (n = 9), an MTD of 60mg was established on the dose-limiting toxicities of hyperglycemia (n = 1) and stomatitis (n = 1) at 75mg. Paxalisib at 60mg was well-tolerated and adverse events were consistent with other PI3K inhibitor medicines. At the MTD (60mg), the PK profile was linear and dose-proportional with no differences in T max and elimination half-life under fed and fasted conditions. For the overall ITT population, the median progression free survival was 8.4 months (RANO) and 8.6 months (mRANO) and the median overall survival was 15.7 months. In a mITT (n = 22 patients treated with 60mg daily and ≥1 post-baseline assessment), the median PFS was 9.6 months (mRANO). Conclusions: The primary study endpoints were met; PK and safety were consistent with prior clinical experience. The MTD showed encouraging clinical activity, prolonging PFS and improving OS. Further efficacy confirmation of paxalisib 60 mg QD in newly diagnosed glioblastoma in a pivotal trial is ongoing (GBM AGILE, NCT03970447). Clinical trial information: NCT03522298.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.2047
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 5
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    INDIGO: A global, randomized, double-blind, phase III study of vorasidenib (VOR; AG-881) vs placebo in patients (pts) with residual or recurrent grade II glioma with an isocitrate dehydrogenase 1/2 (IDH1/2) mutation.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS2574-TPS2574
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS2574-TPS2574
    Abstract: TPS2574 Background: Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options consist of surgery followed by observation (“watch and wait”) for pts with lower risk for disease progression or post-operative chemo-radiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (m IDH1/2) occur in approximately 70% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate (2-HG). VOR, an oral, potent, reversible, brain-penetrant inhibitor of mIDH1/2, was evaluated in 76 pts with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at doses of 〈 100 mg daily. Preliminary clinical activity was observed in non-enhancing glioma pts in both studies, most recently with an objective response rate (ORR) of 30.8% at 50 mg QD in the perioperative study and 〉 90% 2-HG suppression at this dose level relative to untreated control samples (Mellinghoff et al., J Clin Oncol 2019). Methods: Approximately 366 pts will be randomized 1:1 to VOR (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria include: age ≥12 years; grade 2 oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed m IDH1/2 status; ≥1 prior surgery for glioma within the previous 5 years but no other anticancer therapy; Karnofsky performance status ≥80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the VOR arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint is progression-free survival assessed by independent review. Secondary endpoints include safety and tolerability, tumor growth rate assessed by volume, time to next intervention, ORR, overall survival, quality of life assessed by the Functional Assessment of Cancer Therapy–Brain questionnaire, and plasma pharmacokinetics. Exploratory endpoints include seizure activity and neuro-cognitive function. Clinical data will be reviewed regularly throughout the study by an independent data monitoring committee. The study is currently enrolling pts in the US, with additional countries planned (NCT04164901). Clinical trial information: NCT04164901 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.TPS2574
    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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  • 6
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    Low-intensity focused ultrasound with systemic microbubble oscillators for blood-brain barrier disruption for liquid biopsy in glioblastoma (LIBERATE).
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS2084-TPS2084
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS2084-TPS2084
    Abstract: TPS2084 Background: Liquid biopsy in glioblastoma (GBM) is hindered by a lack of requisite circulating-free DNA (cfDNA) levels in blood due to the blood-brain barrier (BBB). This results in challenges to the identification of blood-based biomarkers and the development of novel biomarker-driven systemic therapies. Real-time image-guided low intensity focused ultrasound (LIFU) combined with IV microbubble oscillators (DEFINITY), non-invasively causes BBB disruption (BBBD). This clinical trial aims to evaluate the utility of LIFU for increasing cfDNA in blood for liquid biopsy in GBM. Methods: LIBERATE is a prospective, multi-center, self-controlled, ongoing, pivotal trial evaluating safety and technical efficacy of LIFU for BBBD to increase cfDNA in blood for GBM. Patients aged 〉 18-80 years with suspected GBM planned for tumor biopsy or resection at eleven centers in North America are being included. Patients with multifocal tumors or tumors arising from deep midline, thalamus, cerebellum, or brainstem are excluded. Patients are administered IV oscillating microbubbles for enhancing sonication, after which MR-guided BBBD using a 220 kHz LIFU device is performed with real-time acoustic feedback for effective cavitation. Before and after procedure, phlebotomies and MRI brain are performed to evaluate outcomes. The primary study endpoint is defined, per subject, as the ratio between their cfDNA level in blood 1-hour post-LIFU compared to cfDNA level in blood pre-procedure. The primary study hypothesis is that BBBD with LIFU leads to ≥2-fold increase in cfDNA in blood. The secondary hypothesis is that there exists ≥75% agreement between biomarker pattern in cfDNA sample from 1-hour post-LIFU sample and biomarker pattern in tumor tissue obtained later. The trial has been powered to evaluate both primary and secondary hypotheses. Based on an assumed true agreement rate of 91% and a one-sided alpha of 0.025, an exact test for binomial proportions provides a sample of N=50 with 84% power for the secondary hypothesis. Exploratory endpoints include (1) sensitivity of detection of known somatic mutations in cfDNA from blood samples collected before and after LIFU, (2) estimation of cfDNA levels post-LIFU in samples collected at 30 minutes, 1 hour, 2 hour, and 3 hour to determine time of greatest yield, (3) correlation of MRI parameters related to grading of BBBD and biomarkers positive in cfDNA from post-LIFU blood samples. Patient enrollment commenced in 2022 and 7 patients have been recruited by 02/13/2023. Clinical trial information: NCT05383872 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.TPS2084
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 7
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    Simultaneous molecular alterations in solid tumors with IDH1 or IDH2 mutations.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 11609-11609
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 11609-11609
    Abstract: 11609 Background: Somatic mutations in IDH1 or IDH2 genes are prevalent in diverse solid tumors and implicated in tumorigenesis. Therapeutic responses to IDH inhibitors are infrequent plausibly due to presence of simultaneous alterations activating compensatory molecular pathways. Methods: We retrospectively reviewed results from clinical genomic profiling with targeted next-generation sequencing in two independent data sets of archival formalin-fixed paraffin-embedded (FFPE) tumor samples (Ion Torrent 〈 50 genes, 300; FoundationOne 〈 343 genes, 30; Oncomine 128 genes, 4) and plasma liquid biopsies (Guardant360 〈 73 genes panel, 337 samples) from patients with solid tumors of all stages. Results: In 334 FFPE samples the most represented cancers were gliomas (50%), melanomas (14%), cholangiocarcinomas (11%), and non-small cell lung cancer (NSCLC, 6%). In 296 IDH1-mutated FFPE samples the most frequent simultaneous alterations were in TP53 (45%), BRAF (11%), KRAS (9%), and PIK3CA (26, 9%). In the most represented IDH1-mutated tumor types commonly altered genes were TP53 (66%) in gliomas, BRAF (53% [V600K/R 30%, V600E 19%]) in melanomas, PIK3CA (13%), CDKN2A (13%) in cholangiocarcinomas and KRAS (65%) in NSCLC. In 38 IDH2-mutated FFPE samples the most frequent simultaneous alterations were in TP53 (32%), and KRAS (16%). In 337 plasma samples the most represented cancers were NSCLC (39%), cholangiocarcinoma (13%), and breast cancer (8%). In 172 IDH1-mutated plasma samples the most frequent simultaneous alterations were in TP53 (40%), KRAS (23%), EGFR (16%) and BRAF (16%). In the most represented IDH1-mutated tumors commonly altered genes were TP53 (48%), KRAS (37%) in NSCLC and TP53 (37%), KRAS (24%), BRAF (18%) in cholangiocarcinoma. In 161 IDH2-mutated plasma samples the most frequent simultaneous alterations were in TP53 (43%), EGFR (20%), and KRAS (19%). In the most represented IDH2-mutated tumors commonly altered genes were TP53 (43%), EGFR (32%), KRAS (18%) in NSCLC and TP53 (18%), ESR1 (18%), KRAS (18%) in breast cancer. There were 4 tumors with IDH1 and IDH2mutations. Conclusions: IDH1 and IDH2 mutations often coexist with simultaneous oncogenic alterations including these in potentially druggable molecular targets.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.11609
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 8
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    An inhibitor of oxidative phosphorylation exploits cancer vulnerability
    Springer Science and Business Media LLC ; 2018
    In:  Nature Medicine Vol. 24, No. 7 ( 2018-07), p. 1036-1046
    Details
    In: Nature Medicine, Springer Science and Business Media LLC, Vol. 24, No. 7 ( 2018-07), p. 1036-1046
    Type of Medium: Online Resource
    ISSN: 1078-8956 , 1546-170X
    URL: Article
    DOI: 10.1038/s41591-018-0052-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 1484517-9
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  • 9
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    A phase I/IIa study to evaluate the safety and efficacy of blood-brain barrier (BBB) opening with the SonoCloud-9 implantable ultrasound device in recurrent glioblastoma patients receiving IV carboplatin.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 2049-2049
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 2049-2049
    Abstract: 2049 Background: Low intensity pulsed ultrasound (LIPU) in conjunction with intravenous microbubbles can transiently and reversibly disrupt the blood-brain barrier (BBB), allowing for an increase in the tissue concentration of chemotherapy agents in the brain. Mass spectrometry data from preclinical models (mouse, swine) showed a 〉 5x enhancement in carboplatin brain concentrations, which correlated well with the spatial distribution of a Gadolinium (Gd) contrast agent used for magnetic resonance imaging (MRI). Methods: The primary objective of this phase I/IIa study (NCT03744026) was to demonstrate the safety of BBB disruption using LIPU in patients with recurrent glioblastoma. This study was a 3+3 design using escalating numbers (3, 6, 9) of activated 1 MHz ultrasound emitters. Nine patients were treated in the escalation phase and another 12 patients were treated with 9 emitters in the expansion phase. Eligibility included recurrent GBM (any recurrence) with a maximum tumor size of 〈 70 mm. The SonoCloud-9 device (CarThera, Paris, France) was implanted during tumor debulking/resection surgery and replaced the bone flap, with the device targeting the tumor and surrounding peritumoral brain. The device was activated every four weeks for a duration of 270 seconds, concomitantly with IV DEFINITY microbubbles (10 ml/kg), to disrupt the BBB prior to administration of carboplatin (AUC 4-6). MRI was performed to verify safety and evaluate efficacy of BBB disruption with Gd enhancement. Results: No DLTs were observed. The overall tolerance of the SonoCloud-9 implant was good, with two transient, manageable grade 3 wound infections and one grade 1 acquired meningocele event considered as probably related to the overall procedure. The most frequent neurologic adverse events were grade 1 blurred vision (5%) and dizziness (5%). Conclusions: Significant Gd enhancement was observed after more than 90% of sonication sessions, suggesting effective BBB disruption and carboplatin enhancement. Clinical trial information: NCT03744026.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.2049
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Phase I/II study to evaluate the safety and clinical efficacy of atezolizumab (atezo; aPDL1) in combination with temozolomide (TMZ) and radiation in patients with newly diagnosed glioblastoma (GBM).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 2511-2511
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 2511-2511
    Abstract: 2511 Background: Immunotherapy strategies such as PD-1/PD-L1 inhibition may work synergistically with radiation, which is known to increase antigen presentation and promote a pro-inflammatory tumor microenvironment. This trial evaluated the safety and clinical efficacy of concurrent atezo with radiation therapy and TMZ followed by adjuvant atezo and TMZ in patients with newly diagnosed GBM, unselected for MGMT status. Methods: Eligibility criteria included patients with newly diagnosed GBM age 〉 18 yrs who had undergone only surgery. The primary endpoint was safety in Phase I (n = 10) and OS in Phase II (n = 50). Secondary endpoints included progression free survival (PFS), overall response rate (ORR), and duration of response. All 60 patients were evaluated for efficacy. Correlative endpoints include profiling of tumor immune cell populations and peripheral blood for evaluation of circulating chemokines/cytokines. Results: 60 patients were enrolled. With median follow-up time of 16.7 months (data cutoff = 30 Dec 2019), 24 patients had died and 32 had progressed. Median OS was 17.1 months (95% CI: 13.9, not reached). Median PFS was 9.7 months (95% CI: 7.6-15). Median PFS in MGMT methylated patients (n = 18) was 16.7 months (95% CI: 7.85, not reached) and 7.9 months (95% CI: 6.70-12.4) in MGMT unmethylated patients (n = 33). Treatment-related adverse events with maximum CTCAE grade 〉 3 occurred in 33 patients; the most common were LFT elevation (n = 5) and lymphopenia (n = 23). To date, 17 of the enrolled 60 patients underwent re-resection post treatment with atezo. The matched paired tumor analysis of pre and post treatment tissue will provide valuable insights into mechanisms of anti-PD-L1 therapy resistance. Tumor immunocorrelative studies are pending. Conclusions: Concurrent use of atezo with radiation and TMZ was tolerable and demonstrated modest efficacy. Clinical trial information: NCT03174197 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.2511
    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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