GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Society of Clinical Oncology (ASCO)  (16)
Material
Publisher
  • American Society of Clinical Oncology (ASCO)  (16)
Person/Organisation
Language
Years
Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Phase I/II study of nab-paclitaxel combined with S-1 as adjuvant chemotherapy in diffuse type of stage III gastric or gastroesophageal junction adenocarcinoma.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e16064-e16064
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e16064-e16064
    Abstract: e16064 Background: Diffuse type (Lauren's classification) of gastric adenocarcinoma (GAC) or gastroesophageal junction adenocarcinoma (GEJ) has a poorer prognosis than intestinal type of GAC or GEJ. Studies have shown that nab-paclitaxel combined with S-1 has a synergistic anti-tumor effect on advanced gastric cancer. We designed this trial to evaluate the efficacy and safety of nab-paclitaxel plus S-1 as adjuvant chemotherapy in diffuse type of stage III GAC or GEJ. Methods: This study was a multi-center, open-label, phase I/II study. The results of the phase I dose escalation study have already been reported, and the recommended phase II dose (RP2D) of nab-paclitaxel is 260mg/m 2 . Patients with stage III diffuse type GAC or GEJ after D2 dissection and achieved R0 resection were included in this study. S-1 monotherapy was used as adjuvant therapy in the first cycle. If absence of grade3/4 treatment-related adverse events (AEs) of S-1 monotherapy, nab-paclitaxel (260mg/m 2 , d1, q3w) and S-1 [body surface area (BSA) 〈 1.25 m 2 , 80mg/d; BSA 1.25–1.5 m 2 , 100mg/d; BSA 〉 1.5 m 2 , 120mg/d; d1-14, q3w] were administered for 6 cycles. Then patients still received S-1 monotherapy for 8 cycles. In phase II study, the primary endpoint was 1-year disease free survival (DFS) rate, and the secondary endpoints were 3-year DFS rate and safety. Results: From January 2021 to February 2023, a total of 42 patients were enrolled in this analysis (3 patients in nab-paclitaxel 260mg/m 2 dose group in phase I and 39 patients in phase II). The median age (range) was 53 (29~69) years, 18 patients (42.86%) were stage IIIA, 10 patients (23.81%) were stage IIIB and 14 patients (33.33%) were stage IIIC. The median follow-up time was 13.26 months. As of January 2023, 12 patients experienced recurrence. The 1-year-DFS rate was 74.07%, median DFS and 3-year-DFS rate were not reached. The incidence of adverse effects (AEs) was 78.57% (33/42), and the rate of grade 3-4 AEs was 42.86% (18/42). The most common AEs were neutropenia and leukopenia. In addition, we performed next generation sequencing (NGS) for 5 relapsed patients, and 5 non-relapsed patients who were matched to the relapsed patients. The results showed that the mutant rates of tumor supressor gene CDH1, ARID1A, KMT2D, and TP53 in non-relapsed patients were higher than that in relapsed patients. The positive rate of ctDNA were 60% in relapsed patients, but no ctDNA was detected in non-relapsed patients. Conclusions: Adjuvant chemotherapy with nab-paclitaxel and S-1 followed by S-1 monotherapy exhibited promising clinical efficacy, with acceptable tolerability. This study deserves further investigation and follow up for diffuse type of GAC or GEJ. Clinical trial information: NCT03977220 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e16064
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    The response of PD-1 inhibitor combined with Radiotherapy and GM-CSF(PRaG) with or without IL-2 in microsatellite stable metastatic colorectal cancer: Analysis of pooled data from two phase II trials.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e15561-e15561
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15561-e15561
    Abstract: e15561 Background: Immunotherapy has improved outcomes for metastatic colorectal cancer(mCRC) patients with MSI-H/dMMR but has not been effective in MSS/pMMR tumors, which comprise 95% of mCRC. In metastatic cancers, radiotherapy can be used as a local therapy and a sensitizer to PD-1/PD-L1 inhibitors. The synergistic effects of radiotherapy and PD-1/PD-L1 inhibitors can be reinforced by adding cytokines like granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2(IL-2). Our previous PRaG trial demonstrated that PD-1 inhibitors in combination with radiotherapy and GM-CSF could improve clinical response in patients with advanced refractory solid tumors. We found that mCRC patients with MSS/pMMR could also benefit from the PRaG regimen. Methods: Patients of mCRC with MSS/pMMR were collected from the PRaG trial and PRaG 2.0 trial. A treatment cycle consisted of radiotherapy (5 or 8Gy×2-3f) delivered for one metastatic lesion, PD-1 inhibitor dosing within one week after completion of radiotherapy, GM-CSF 200μg subcutaneous (SC) injection once daily for 14 days(d1-14), or GM-CSF 200μg (d1-7), and then sequentially followed by IL-2 200 million IU SC once daily for 7 days(d8-14). PRaG regimen was repeated every 21 days for at least 2 cycles until no appropriate lesions for irradiation or reached the tolerance dose. Pooled analysis of response rate (ORR), median progression-free survival (PFS), and treatment-related adverse eventswere calculated. Results: With the cutoff date of 31 December 2021, a total of 9 mCRC patients with MSS/pMMR were enrolled. All of the patients completed at least 2 cycles of PRaG therapy and one evaluation. The median follow-up was 7.6 months (95%CI, 3.8, 11.4). The ORR was 22.2%, and the disease control rate(DCR) was 66.7%. The median PFS was 5.6 months (95%CI, 1.5 to 9.7). One patient got complete remission, with PFS over 17months. Treatment-related adverse events (TRAE) occurred in 7 of 9 (77.8%) patients. One patient (11.1%) occurred Grade3 TRAE of renal insufficiency. Conclusions: Our preliminary results suggest that the PRaG regimen could improve clinical outcomes in mCRC patients with MSS/pMMR with acceptable toxicity.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e15561
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e16094-e16094
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16094-e16094
    Abstract: e16094 Background: Hepatoid adenocarcinoma (HAC) is a rare pathological subtype of extrahepatic tumor, featured by hepatoid differentiation and α-fetoprotein (AFP)-production. Hepatoid adenocarcinoma of the stomach (HAS), accounting for 0.17 to 15% of gastric cancers, is the most common subtype of HAC, and has attracted increasing attention duo to its high degree of malignancy. Compared with classic gastric cancer (GC), HAS showed a higher rate of vascular invasion, lymph node metastasis, and liver metastasis, with only 9% survival at 5 years. In this study, we aim to investigate the molecular features of HAS and identify the potential therapeutic targets for HAS. Methods: We conducted whole-exome sequencing (WES) of 40 paired tumor and normal samples, including 25 HAS, 6 HAC of other organ and 9 AFP-producing gastric cancer (AFPGC). All patients underwent radical surgery at Shanghai Zhongshan Hospital between July 2013 and September 2017. qRT-PCR, Western blot and immunohistochemistry were detected to explore MUC19 expression in HAS. CCK8 assay, Transwell assay, immunofluorescence assay and subcutaneous xenograft tumor model were used to detect functional effects and the mechanism of MUC19. Results: In HAS patients, the top 5 frequently mutated genes were TP53 (44%), TTN (44%), MUC19 (40%), CCNE1 (28%) and CDC27 (28%). Further compared with TCGA datasets, MUC19, CCNE1, CDC27 mutations were almost undetectable in STAD, CRC and HCC. In terms of CNV analysis, VSTM2B, PLEKHF1, POP4, URI1 and TERT were the most frequently amplificated genes in HAS tumor tissues. Interestingly, amplification of 4 genes (VSTM2B, CCNE1, LEKHF1, POP4), which located in chr19q12, was significantly associated with poor prognosis. The tumor mutational burden (TMB) levels and AFP expression of HAS and AFPGC patients were no significantly different, while patients with higher TMB had a remarkably longer overall survival ( p= 0.0065). Moreover, we found MUC19 expression was positively correlated with AFP levels in HAS and MUC19 promoted the transcription of AFP in GC cells. Mechanistically, MUC19 contributed to the aggressive malignancy phenotypes of GC cells through activating the Wnt/β-catenin signaling pathway. Conclusions: MUC19 may be a potential target for HAS diagnosis and treatment. Amplification of genes located in chr19q12 occurred frequently in HAS and were associate with poor prognosis. TMB was sensitive for the overall survival of HAS patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e16094
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Efficacy and safety of tislelizumab plus cetuximab and irinotecan in patients with previously treated RAS wild-type advanced colorectal cancer: Preliminary findings of a phase II, single-arm study.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 3566-3566
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 3566-3566
    Abstract: 3566 Background: For adequately treated patients (pts) with advanced colorectal cancer, the current third-line treatment standard of TKIs or TAS-102 administration has a low clinical objective response rate and its effectiveness seems to be limited. Preclinical studies have suggested that EGFR pathway blockage and immune checkpoint inhibition have synergistic therapeutic effects in these pts. The purpose of this study was to examine the efficacy and safety of tislelizumab (anti-PD-1 antibody) plus cetuximab and irinotecan in pts with previously treated RAS wild-type advanced colorectal cancer. Methods: This is an open-label, single-arm, phase II study. RAS wild-type advanced colorectal cancer pts with at least two previous lines of therapy were included in this study and administered with tislelizumab plus cetuximab and irinotecan until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) (RESCIT 1.1). Secondary endpoints included DCR, PFS, OS and safety. Results: In total, 35 eligible RAS wild-type advanced colorectal cancer pts were enrolled from March 2021 to September 2021. The median age was 58 years. All 35 pts were identified as BRAF/RAS wild-type, and 33 (94%) had left-sided colon cancer. The percentages of pts with second-line, third-line and ≥fourth-line previous treatments were 37%, 49%, and 14%, respectively. Thirty-four pts (97%) had received targeted therapies previously, including 29 (83%) with anti-EGFR therapy. By December 31, 2021, 2 pts had withdrawn from the study for personal reasons, and the remaining 33 were evaluated for efficacy. Twelve of the 33 (36.4%) pts achieved clinical partial remission and 14 (42.4%) achieved stable disease; disease progression occurred in 6 pts and 1 patient died. The ORR was 36.4% and the DCR was 78.8%. Until December 31, 2021, 23 pts continued treatments, and the median PFS was not reached. Among the 33 treated pts, 32 (97.0%) had treatment-related adverse events (AEs). Common AEs included rash (n = 32), fatigue (n = 29), decreased appetite (n = 24), nausea (n = 24), diarrhea (n = 13), liver dysfunction (n = 10), vomiting (n = 7), leukopenia (n = 7), anemia (n = 6), paronychia (n = 5), oral mucositis (n = 4), and neutropenia (n = 4). Four (12%) of the 33 pts reported grade ≥3 AEs, including rash (n = 1), neutropenia (n = 2) and vomiting (n = 1). Conclusions: Tislelizumab plus cetuximab and irinotecan shows an encouraging clinical efficacy and tolerable safety in previously treated pts with RAS wide-type advanced colorectal cancer. Clinical trial information: NCT05143099.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.3566
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Genomic alterations and clinical correlations of Chinese patients with hepatoid adenocarcinoma of the stomach/alpha-fetoprotein gastric cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e13514-e13514
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e13514-e13514
    Abstract: e13514 Background: Hepatoid adenocarcinoma of stomach (HAS) is a rare subtype of gastric cancer (GC) with poor prognosis due to frequent liver metastasis. HAS, recognized as an extrahepatic cancer that resembles hepatocellular carcinoma (HCC), is characterized by solid sheet-like growth structures with hepatoid differentiation and excessive production of alpha-fetoprotein (AFP). This HAS subtype of GC (AFPGC) is genetically distinct compared to other common GC but requires more evidences for better characterization. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues were collected from 25 HAS and 9 AFPGC patients at Zhongshan Hospital from July 2013 to August 2017 for whole exome sequencing (WES) test. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: Our cohort included 25 males and 9 females who had undergone surgical treatment. The 25 HAS patients had a median age of 66.5 years (range 48-82) and the 9 AFPGC patients had a median age of 64 years (range 52-76). Patients with AFP 〉 20 had a significantly better overall survival (OS) compared with patients with AFP≤20. The most frequently mutated genes were TP53 (44%), TTN (44%), and MUC19 (30%) in HAS tumor samples and CDC27 (44%), NKX2-3 (44%), and TTN (44%) in AFPGC samples. Patients with URI1 or POP4 alterations had a significantly poorer OS than patients without those genes mutations (7.6 months vs. 19.8 months, p = 0.016, and 10.9 months vs. 19.7 months, p = 0.038, respectively). However, patients with SPTA1 alterations had a significantly better OS compared to patients without SPTA1 alterations (27.6 months vs. 15.8 months, p = 0.042). Patients with higher tumor mutational burden (TMB) (≥3.9 muts/Mb) had a significantly better OS compared with patients with lower TMB ( 〈 3.9 muts/Mb), which indicated TMB may be an independent prognostic factor (HR: 0.032, 95%CI: 0.003-0.33, p = 0.004). Conclusions: Our study revealed the genomic profile of HAS/AFPGC patients. The most frequently mutated genes in HAS and AFPGC were different, which helps to better characterize these tumors. AFP and TMB may be potential biomarkers for predicting patients’ prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e13514
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Preoperative chemotherapy prior to primary tumor resection for asymptomatic synchronous unresectable colorectal liver-limited metastases: A multicenter randomized controlled trial.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 132-132
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 132-132
    Abstract: 132 Background: Most recently, there were 3 reports of prospective randomized clinical trials comparing the effects of primary tumor resection (PTR) for multiorgan metastatic colorectal cancer followed by chemotherapy with chemotherapy alone, but the results differed and unconvincing due to the prematurely study termination and research protocol changes. PTR was preferably performed for patients with asymptomatic synchronous unresectable colorectal liver-limited metastases (CRLMs) with conversion therapy purpose, including the CELIM, OLIVIA and our study (J Clin Oncol 2013;31:1931-8). This randomized phase III study investigated the superiority of preoperative chemotherapy prior to PTR for patients with asymptomatic synchronous unresectable CRLMs. Methods: Patients with asymptomatic synchronous unresectable CRLMs were randomly assigned to receive pre-PTR chemotherapy (arm A) or upfront PTR (arm B). Chemotherapy regimens of mFOLFOX6 plus cetuximab, mFOLFOX6 plus bevacizumab or mFOLFOX6 alone were decided according to the RAS genotype. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), tumor response, disease control rate (DCR), liver metastases resection rate, surgical complications and chemotherapy toxicity. Results: Between June 2012 and June 2018, a total of 320 patients were randomly assigned to arm A (160 patients) or arm B (160 patients). The cutoff date for survival data was June 2021, the median follow-up time was 36.2 months. Patients were well balanced. For the intention-to-treat population, the median PFS, median OS, and 3-year OS rates were 9.9 months, 28.0 months, and 37.0%, respectively. The median PFS in arm A was significantly improved compared with arm B (10.5 v 9.1 months; hazard ratio [95% CI, 0.60 to 0.95], 0.76; P = 0.013). Patients in arm A also had a significantly better DCR (84.4% v 75.0%; P = 0.037). The median OS was not significantly different (29.4 v 27.2 months; hazard ratio [95% CI, 0.58 to 1.01] , 0.77, P = 0.058), and the objective response rates were also not significantly different (53.1% v 45.0%; P = 0.146). The actual resection rate of liver metastases was not significantly different (21.9% v 18.1%; P = 0.402). There were mild morbidities and no 30-day postoperative mortalities in both arms. The rate of complications was not significantly different (37.7% v 30.8%, P = 0.201). The incidence of Clavien–Dindo 3-4 complications also did not reach statistical significance (4.5% v 3.8%, P = 0.759). Overall the observed toxicity was mostly mild. There was no significant difference in the overall incidence of predefined grade 3/4 events (42.2% v 40.4%, P = 0.744). There were no grade 5 events in either arm. Conclusions: For asymptomatic synchronous unresectable CRLMs, Pre-PTR chemotherapy improved the PFS compared with upfront PTR. Clinical trial information: NCT01307878 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.132
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Safety and efficacy of loading-dose thymosin α1 in patients with advanced and refractory solid tumors with lower absolute T lymphocyte.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e14543-e14543
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e14543-e14543
    Abstract: e14543 Background: Nowadays immune checkpoint inhibitors (ICIs) has been reshaping the paradigm of cancer therapy, including various refractory advanced solid tumors. Many studies have shown that low baseline peripheral blood-based immune cells, such as lymphocytes, was one of the most relevant parameters associated with immunotherapy efficacy and prognosis. Thymosin a1, a synthetic polypeptide, has been demonstrated to increase the number of peripheral lymphocytes, especially T cells in patients with solid malignancies. In this current study, we aimed to evaluate the efficacy of loading-dose thymosin a1 (Ta-1) on peripheral lymphocytes and subpopulations in advanced solid tumors and identify how it affects the clinical outcome. Methods: Participants with confirmed the number of peripheral blood-based CD3 + T cells less than 0.5 ´ 10 9 /L, advanced solid tumors that had progressed after standard treatment, or intolerance were enrolled. In this study, those received 3.2mg thymosin α1 subcutaneously in a daily loading dose for 7 days, and the peripheral blood immune indexes were detected on the ninth day. Afterwards, these patients were decided whether to receive radiotherapy and PD-(L)1 inhibitor based on the clinician’s judgement. The primary endpoint was overall survival (OS) and the secondary endpoint were treatment-related adverse events and a panel of circulating lymphocytic subpopulations. Results: As of the cutoff date of February 6 th , 2023, a total of 27 patients were enrolled.The median age of them was 61 years old (range: 39-78). Twenty-two patients (81.5%) had poor ECOG performance status of 2 and 3. Eight (29.6%) patients had received at least 3 prior lines of systematic treatments. Most patients (19, 70.3%) had 2 or more metastatic sites. After treated daily with 3.2mg Ta-1 for 7 days, twenty-four patients (88.9%) were subsequently received radiotherapy and PD-(L)1 inhibitors. By data cut-off, median duration of follow-up was 19.2 months (95%CI: 6.2 to NA;), and median OS was 19.6 months (95%CI: 6.6 to 27.2). We found that peripheral CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells, and natural killer (NK) cells were significantly increased after Ta-1 treatment. In an attempt to identify whether the increasing number of lymphocytes after Ta-1 treatment affects the clinical outcome, we compared the subgroup with increasing rate≥30 with that 〈 30%, which showed a trend of longer median OS in ≥30 subgroup than 〈 30% (19.6 months vs 3.9 months). No Grade ≥3 treatment-related adverse events occurred in all enrolled patients when treated with loading-dose Ta-1. Conclusions: In this study, we demonstrated that a daily loading-dose Tα-1 treatment increased the number of peripheral lymphocytic subpopulations, and this effect appears to benefit survival outcomes, shedding new light for patients with advanced or refractory solid tumors when initiated ICI treatment.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e14543
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    A multicenter, phase II trial of RC48-ADC combined with radiotherapy, PD-1/PD-L1 inhibitor, GM-CSF, and sequential IL-2 (PRaG3.0 regimen) for salvage therapy in patients with HER2-expressing advanced solid tumors.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e14614-e14614
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e14614-e14614
    Abstract: e14614 Background: Cancer immunotherapy has emerged as one of the most promising approaches in many kinds of advanced tumors. The PRaG therapy is an innovative cancer immunotherapy, when combined with radiotherapy, PD-1/L1 inhibitor and GM-CSF to generate the desired in situ vaccine effect to activate the immune response and modulate the tumor microenvironment. Previous studies have showed encouraging efficacy of the PRaG regimen in the treatment of advanced refractory tumors. RC48-ADC, an anti-HER2 antibody-drug conjugate with MMAE as cytotoxic payload has been recently demonstrated that ADCs are also able to induce immunogenic cell death and widespread release of cancer cell antigens, synergize with immunotherapy by promoting effector T-cell activation. The aim of this study is to explore efficacy and safety of PRaG3.0 regimen for therapy of HER2-expressing advanced solid tumors. Methods: Participants with advanced, confirmed HER2-expressing (IHC3+, 2+ or 1+) solid tumors that had progressed after standard of care, or intolerance were enrolled. In the cycle, those received RC48-ADC (2.0 mg/kg d1, every 3 weeks), then HFRT (2-3 doses of 5-8Gy) was delivered for one metastatic lesion every other day, followed by GM-CSF (200 μg d3-7), sequential IL-2 (2million IU d8-12), and PD-1/L1 inhibitor was dosing within one week after completion of HFRT. After RC48-ADC combined with PD-1/L1 inhibitor sequential cytokines for at least 6 cycles, then maintenance with PD-1/PD-L1 inhibitor was administered until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Results: As of Jan 2023, a total of 32 patients (n=6 for gynecological cancer, n=5 for pancreatic cancer, n=21 for other cancers) were enrolled, 26 of them completed at least 1 tumor assessment. The ORR was 38.5%, and the disease control rate was 69.2%. The ORR was 66.7% in gynecological cancer, 25.0% in pancreatic cancer, and 31.3% in other cancers. Notably, patients who were HER2 IHC1+ responded similarly to those who were IHC2+~3+, with ORR of 43.8% and 30.0%, respectively. Median progression-free survival was 7.2 months (95%CI: 4.9, 9.5). The most common treatment-related adverse events (TRAEs) included fatigue (28.1%), fever (28.1%), alopecia (28.1%) and anorexia (18.8%). Grade ≥3 TRAEs occurred in two patients (6.3%). In addition, activated plasmacytoid dendritic cell was significantly higher at baseline in responders (CR+PR) vs. nonresponders (SD+PD). Conclusions: The schedule of RC48-ADC was changed from once every 2 weeks to once every 3 weeks, and was still effective with significantly reduced side effects. These preliminary results suggest that PRaG3.0 regimen has a manageable safety profile and enhancing potential sensitivity in pretreated patients with HER2-expressing cancers. Clinical trial information: NCT05115500 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e14614
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Toripalimab with chemotherapy as first-line treatment for advanced biliary tract tumors: Update analytic results of an open-label phase II clinical study (JS001-ZS-BC001).
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e16170-e16170
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e16170-e16170
    Abstract: e16170 Background: A phase II clinical study was conducted to evaluate the safety and efficacy of toripalimab, a novel PD-1 inhibitor, combined with chemotherapy in patients with advanced biliary tract cancers (aBTCs) (NCT03796429). The preliminary results indicated the combination treatment is well tolerable and effective. Methods: Treatment naive patients with aBTCs received toripalimab (240mg intravenously every three weeks) combined with chemotherapy (gemcitabine 1000 mg/m2 d1, d8 + S-1 40-60mg bid D1-14, Q21d). The treatment continued until the disease progress or having intolerable effects. The primary endpoints of the study were progression free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), safety and treatment biomarkers. Results: At data cutoff (January 24, 2021), fifty aBTC patients were enrolled at Shanghai Zhongshan Hospital. Among these patients, 56% are males. The median age of the study participants was 62 years of age. The median follow-up time was 10 months (ranged from 4 to 19 months). The primary tumor type was intrahepatic cholangiocarcinoma (ICC) accounting for 48% of total cases, followed by gallbladder cancer (GBC) (40.0%), and extrahepatic cholangiocarcinoma (ECC) (12.0%). At the time of data collection, 48 eligible patients were included for data analysis. The median PFS was 7.0 months（95%CI, 5.5-9.1 months）and median OS was 16.0 months (95%CI, 12.1 to unreachable). The ORR was 27.1 % and disease control rate was 87.5% including 13 partial response (PR) and 29 stable disease (SD) cases. The most treatment related AEs (TRAE) were leukopenia (92.0%), anemia (86.0%) and rash (52.0%). Grade III/IV non-hematological TRAEs were seen in 12 patients (24.0%), including rash (n = 3), infection (n = 6), immune-related colitis (n = 1), immune-related pneumonitis (n = 1) and mucositis (n = 1). Grade III/IV hematological TRAEs were seen in 62% patients. 6 patients discontinued the study drug due to TRAE. Serious adverse events (SAE) were seen in 8 patients and 2 patients died of biliary obstruction complicated with infection. Forty-nine patients were included in biomarker analysis. The most mutated genes were TP53 (51%), KRAS (20%), CDKN2A (18%) and SMAD4 (16%). Patients with activated PI3K signaling pathway had significantly shorter PFS (P = 0.026). Tumor mutational burden (TMB) could not serve as a predictor for the efficacy of immunotherapy combined with chemotherapy. Conclusions: The clinical study of toripalimab combined with chemotherapy continued to show tolerance and efficacy in patients with aBTCs. Gene mutation profiling by NGS suggested mutated PI3K pathway might assocate with shorter PFS. Clinical trial information: NCT03796429.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.e16170
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    PD-1 inhibitors combined with radiotherapy and GM-CSF, sequentially followed by IL-2 (PRaG 2.0) regimen in advanced refractory solid tumors: A prospective, multicenter, single-arm clinical trial.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 2603-2603
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2603-2603
    Abstract: 2603 Background: Low frequency of durable responses in patients treated with immune checkpoint inhibitors demands taking complementary strategies in order to boost immune responses against cancer. Our previous PRaG trial also demonstrated that PD-1 inhibitors in combination with radiotherapy and granulocyte macrophage-colony stimulating factor (GM-CSF) could improve clinical response in patients with advanced refractory solid tumors (ChiCTR1900026175). In an effort to further enhance efficacy, we conducted the PRaG 2.0 trial (ClinicalTrials.gov: NCT04892498) and optimized the PRaG regimen by incorporating interleukin-2 (IL-2). Methods: The PRaG 2.0 regimen was administered to patients with advanced refractory solid tumors who lacked or were unable to tolerate standard-of-care treatments. A treatment cycle consisted of radiotherapy (5 or 8Gy×2-3f) delivered for one metastatic lesion, PD-1 inhibitor dosing within one week after completion of radiotherapy, GM-CSF 200μg subcutaneous (SC) injection once daily for 7 days, and then sequentially followed by IL-2 2million IU SC once daily for 7 days. PRaG 2.0 regimen was repeated every 21 days for at least 2 cycles until no appropriate lesions for irradiation or reached the tolerance dose of normal tissues. Patients who could not continue radiotherapy and had not yet developed progression disease (PD) allowed PD-1 inhibitors to be continued as maintenance therapy until PD or unacceptable toxicity but no more than one year. The primary endpoint was Progression-Free Survival (PFS). Results: As of 31st October 2022, 51 patients were enrolled in the study, and 42 completed at least one tumor assessment. The median Progression-Free Survival (PFS) was 5.8 months, and the median overall survival (OS) was 13.5 months. The objective response rate (ORR) was 21.4%, and the disease control rate (DCR) was 61.9% according to RECIST version 1.1. Lower plasma levels of Interleukin (IL)-6 and IL-17 at baseline were found to be associated with improved PFS. Treatment-related adverse events (TRAE) experienced in 34 of 42 (78.6%) patients, with 4 patients (9.5%) experiencing Grade ≥ 3 TRAEs. TRAEs leading to discontinuation of all study treatments occurred in three patients (7.1%). Conclusions: The PRaG 2.0 trial demonstrates that PD-1 inhibitors in combination with radiotherapy, GM-CSF, and IL-2 could be a potential treatment regimen for patients with advanced refractory solid tumors, with an acceptable benefit/risk profile. Clinical trial information: NCT04892498 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.2603
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...