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  • American Society of Clinical Oncology (ASCO)  (30)
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  • American Society of Clinical Oncology (ASCO)  (30)
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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 3 ( 2023-01-20), p. 651-663
    Abstract: The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P 〈 .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e14581-e14581
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e14581-e14581
    Abstract: e14581 Background: JS001, a humanized IgG4 anti-PD-1 antibody, showed potent anti-cancer activity in preclinical models. Notably, in vivo study suggests it promotes the proliferation of CD62L-CD45RA- effector memory cell effectively. A phase 1 dose escalation study was conducted to assess its safety, tolerability, pharmacokinetic (PK) profile and preliminary efficacy. Methods: This trial used a 3+3 design across 3 dose levels: 1, 3, 10 mg/kg/dose. At each level, two schedules were assessed: single dose and repeated doses every 2 weeks (up to 6 doses). JS-001 was administered as a 60-minute i.v. infusion. A dose limiting toxicity (DLT) was defined as a Grade≥3 drug-related adverse event (AE) occurring within 28 days of last dosing. Results: At the time of analysis, among 19 patients (pts) enrolled (single dose: 9 pts; multiple doses: 10 pts), no DLT was reported. Most treatment-related AEs were grade 1-2, including fever, diarrhea, rash, influenza-like symptoms, fatigue, mucositis, elevated transaminase and decreased lymphocyte count. One patient experienced grade 3 pneumonia. Although the cause of pneumonia is difficult to determine, and further assessment is ongoing, it resolved after prompt management. No treatment-related death occurred. The preliminary PK profile supports a biweekly schedule, and results in detail are under analyzing. 15 pts with evaluable lesions received response evaluation. Best responses were 1 CR (Hodgkin lymphoma, HL), 5 PR (HL: 3; soft tissue sarcoma, STS: 1; diffuse large B-cell lymphoma: 1) and 5 SD (non-small cell lung cancer: 3; head and neck cancer: 2), yielding a disease control rate of 11/15. Remarkably, a patient with STS achieved dramatic tumor shrinkage after a single injection of JS001. Biomarker analysis is in progress. Conclusions: JS001 is well tolerated and the preliminary efficacy results are promising. Updated data on the expansion cohorts at 3mg/kg and 10mg/kg will be presented. Clinical trial information: NCT02836834. Clinical trial information: NCT02836834.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. 9041-9041
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 36_suppl ( 2022-04-20), p. 362936-362936
    Abstract: 362936 Background: Toripalimab (anti–PD-1) in combination with chemotherapy showed significant improvement in progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced non–small cell lung cancer (NSCLC) regardless of tumor PD-L1 expression. Whole-exome sequencing (WES) was performed to identify correlative biomarkers for survival. Methods: Patients (465 patients) with treatment-naïve, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (309 patients) or placebo (156 patients) in combination with chemotherapy for 4-6 cycles, followed by maintenance of toripalimab or placebo plus standard care until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors included PD-L1 expression status, histology, and smoking status. The primary endpoint was PFS by investigator per RECIST v1.1. Secondary endpoints included PFS by a blinded independent review committee (BIRC), OS, and safety. Results: At the prespecified final PFS analysis (cutoff date Oct 31, 2021), a significant improvement in PFS as assessed by investigator was observed for the toripalimab arm over the placebo arm: HR, 0.49 (95% CI, 0.39-0.61); two-sided p 〈 .0001; and median PFS 8.4 vs. 5.6 months. The 1-year PFS rates were 36.7% vs. 17.2%. PFS as assessed by BIRC was also significantly longer in the toripalimab arm. The improvements of PFS were observed across key subgroups, including histology and PD-L1 expression. At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm: HR, 0.69 (95% CI, 0.52-0.92); two-sided p = .0099; median OS not reached vs. 17.1 months. The incidence of grade ≥ 3 adverse events (AEs; 78.6% vs. 82.1%) was similar between the two arms. AEs leading to discontinuation of toripalimab/placebo (14.3% vs. 3.2%) and fatal AEs (5.5% vs. 2.6%) were more frequent in the toripalimab arm. WES results from 394 available patients revealed that patients with high tumor mutational burden (TMB; ≥ 10 mutations per million base pairs) were associated with significantly better PFS in the toripalimab arm over the placebo arm (median PFS 13.1 vs. 5.5 months; interaction p = .026). In addition, patients with mutations in the FAK-PI3K-Akt pathway or IL-7 signaling pathways achieved significantly better PFS and OS from the toripalimab chemotherapy combination (interaction p values ≤ .01). Conclusions: The addition of toripalimab to chemotherapy in patients with advanced NSCLC provided superior PFS and OS when compared to chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with chemotherapy as first-line therapy for patients with advanced NSCLC without EGFR/ALK mutations. Clinical trial information: NCT03856411.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9003-9003
    Abstract: 9003 Background: Toripalimab in combination with chemotherapy showed significant improvement over chemotherapy alone in progression-free survival (PFS) and overall survival (OS) as first-line treatment of advanced NSCLC at the final PFS analysis of the CHOICE-01 study (NCT03856411). Here we report the final OS analysis. Methods: Patients (n=465) with treatment-naïve, advanced NSCLC without EGFR/ALK mutations were randomized 2:1 to receive toripalimab 240 mg (n=309) or placebo (n=156) in combination with chemotherapy for 4-6 cycles, followed by maintenance toripalimab or placebo plus standard care until disease progression, intolerable toxicity, or completion of 2 years of treatment. Patients from the placebo arm were actively crossed-over to receive toripalimab upon disease progression. The primary endpoint was PFS. The secondary endpoints included OS and safety. Results: By the cutoff date of August 31, 2022, when 283 events triggered the final OS analysis, the median survival follow up was 19.4 months. A significant improvement in OS was observed for the toripalimab arm over the placebo arm: HR=0.73 (95% CI: 0.57-0.93), two-sided p=0.0108, median OS 23.8 vs 17.0 months. A consistent effect on OS, favoring the toripalimab arm, was observed all PD-L1 expression subgroups. The OS benefit is greater in non-squamous NSCLC, HR=0.50 (95% CI: 0.36-0.70), median OS 27.8 vs 15.9 months, whereas no significant difference was found in the squamous subgroup (mOS 19.6 vs 18.1 months) despite a significant PFS improvement. The squamous subgroup had a high 70% crossover rate. No new safety signal was identified since the interim report. The incidence of Grade ≥3 adverse events (AEs) (78.9% vs 82.1%) was similar between the two arms. AEs leading to discontinuation of toripalimab/placebo (14.3% vs 3.2%), fatal AEs (5.5% vs 2.6%), and immune-related (irAEs) (50.6% vs. 21.2%) were more frequent in the toripalimab arm. Whole exome sequencing results indicated patients with mutations in the FAK-PI3K-Akt pathway achieved significantly better OS from the toripalimab arm. Conclusions: The addition of toripalimab to chemotherapy in patients with advanced NSCLC provided significant OS benefit than chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with chemotherapy as 1 st line therapy for advanced NSCLC patients without EGFR/ALK mutations. Clinical trial information: NCT03856411 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 1572-1572
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 1572-1572
    Abstract: 1572 Background: PLELC, a rare and distinct type of primary lung cancer, is characterized by Epstein-Barr virus (EBV) infection. Histologically, it resembles undifferentiated nasopharyngeal carcinomas (NPC). Only a few hundred cases have been reported since its discovery. Due to the extreme rareness, its genomic landscape remains elusive. Methods: Tissue samples of 27 PLELC patients (13 males and 14 females) with various stages (Ib to IV) were subjected to targeted sequencing using a panel consisting of 520 cancer-related genes, spanning 1.6Mb of human genome. Results: Collectively, we identified 184 somatic mutations spanning 109 genes, including 107 SNVs, 12 insertions or deletions (INDELs) and 65 copy-number amplifications (CNAs). Approximately, 50% of patients had CNAs. One patient had no mutation detected from this panel. Except for 2 patients, 1 with HER2 amplification and another with KRAS mutation, no other classic NSCLC driver genes were detected. The most frequently mutated genes were CCND1, TP53, DAXX and NF kBIA, occurring in 30%, 26%, 22% and 22% of patients, respectively. Interestingly, 78% (21/27) patients had mutations in epigenetic regulators. Of the 184 mutations identified, 51 occurred in epigenetics-related genes. Pathway analysis also revealed an enrichment of genes participating in chromatin remodeling and organization. Next, we compared the genomic profile of PLELC with lung adenocarcinoma and EBV positive NPC. The frequency of TP53 mutations was significantly higher in lung adenocarcinoma (68% vs 26%, p = 0.021). Comparing to NPC, PLELC had significantly more mutations in epigenetic regulators. TMB analysis revealed a median TMB of 1.6/Mb, significantly lowered than lung adenocarcinomas (p 〈 0.01). We also assessed PD-L1expression and revealed that 67% had an overexpression of PD-L1. Interestingly, TP53-mutant patients were more likely to associated low PD-L1 expression (p 〈 0.01). Conclusions: In this study, we elucidated a distinct genomic landscape associated with PLELC with no classic NSCLC driver mutation but an enrichment of mutations in epigenetic regulators. The observation of high expression of PD-L1 and lack of canonical druggable driver mutation raises the potential of immunocheckpoint blockade therapy for PLELC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e23048-e23048
    Abstract: e23048 Background: Pemetrexed combined platinum is recommended as first line chemotherapy regimen for non-squamous non-small cell lung cancer. However, the efficacy is variable for individuals. Methods: We conducted a prospective study with 52 consecutive patients enrolled who were histologically confirmed advanced or metastatic lung adenocarcinoma, of whom, 32 had their plasma samples collected both baseline and follow-up when efficacy evaluation. We used a next-generation sequencing to assess the dynamic change of ctDNA across 87 plasma samples. Results: 34 blood samples from 61.5% of patients demonstrated smoking status is an infavorable factor to drug efficacy ( p= 0.02, fisher’s exact test, two-sided). Simultaneously, we found positive correlation between decreased mutation burden and chemotherapy sensitivity (the mean mutation rates of pre chemotherapy, PD, PR, SD and SDA were 4.5, 6.3, 2.1, 1.6 and 2.4, respectively, p= 0.004, one way ANOVA test, two-sided).The mean mutation rates with T 〉 G substitution mutation of pre and post chemotherapy were 1.5 and 0.6 ( p= 0.014, Mann-Whitney U test, two-sided). 34.4% (11/32) individuals harbor those mutation pre chemotherapy, 6 out of them were characterized by DNA repair signatures, of which 83.3% (5/6) cases were positively related to platinum sensitivity. In addition, T 〉 G substitution was still detected from 5 patients at cycle 2, 60% (3/5) individuals were characterized by DNA repair signatures and 2 out of them had better platinum-based chemotherapy response.Neoplastic cells carrying a specific set of somatic mutations were sensitive to platinum treatment, including USP9X (pre vs post chemotherapy: 10.3% vs 0%), ZRSR2 (pre vs post chemotherapy: 6.9% vs 0%) and PIK3C2G (pre vs post chemotherapy: 10.3% vs 0%). Nonetheless, persistence of gene ROBO2 (pre vs post chemotherapy: 10.3% vs 4.6%) may be correlated with tumorigenesis. Conclusions: Dynamic monitoring of ctDNA mutation status may be contributed to advanced or metastatic lung adenocarcinoma patients stratification and prediction for pemetrexed combined platinum as first line chemotherapy regimen.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 9028-9028
    Abstract: 9028 Background: Toripalimab (anti-PD-1) in combination with chemotherapy showed significant improvement in progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced NSCLC regardless of tumor PD-L1 expression. Whole exome sequencing (WES) was performed to identify correlative biomarkers for survival. Methods: Patients (n = 465) with treatment-naïve, advanced NSCLC without EGFR/ALK mutations were randomized 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) in combination with chemotherapy for 4-6 cycles, followed by maintenance of toripalimab or placebo plus standard care until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors included PD-L1 expression status, histology, and smoking status. The primary endpoint was PFS by investigator per RECIST v1.1. Secondary endpoints included PFS by a blinded independent review committee (BIRC), OS and safety. Results: At the prespecified final PFS analysis (cutoff date Oct 31, 2021), a significant improvement in PFS as assessed by investigator was observed for the toripalimab arm over the placebo arm: HR = 0.49 (95% CI: 0.39-0.61), two-sided p 〈 0.0001, median PFS 8.4 vs 5.6 months. The 1-year PFS rates were 36.7% vs 17.2%. PFS as assessed by BIRC was also significantly longer in the toripalimab arm. The improvements of PFS were observed across key subgroups, including histology and PD-L1 expression. At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm: HR = 0.69 (95% CI: 0.52-0.92), two-sided p = 0.0099, median OS not reached vs 17.1 months. The incidence of Grade ≥3 adverse events (AEs) (78.6% vs 82.1%) was similar between the two arms. AEs leading to discontinuation of toripalimab/placebo (14.3% vs 3.2%) and fatal AEs (5.5% vs 2.6%) were more frequent in the toripalimab arm. WES results from 394 available patients revealed that patients with high tumor mutational burden (TMB) (≥10 mutations per million base pairs) were associated with significantly better PFS in the toripalimab arm over the placebo arm (median PFS 13.1 vs 5.5 months) (interaction P = 0.026). In addition, patients with mutations in the FAK-PI3K-Akt pathway or IL-7 signaling pathways achieved significantly better PFS and OS from the toripalimab chemotherapy combination (interaction P values ≤ 0.01). Conclusions: The addition of toripalimab to chemotherapy in patients with advanced NSCLC provided superior PFS and OS when compared to chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with chemotherapy as 1 st line therapy for advanced NSCLC patients without EGFR/ALK mutations. Clinical trial information: NCT03856411.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e15108-e15108
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 11572-11572
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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