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  • American Society of Clinical Oncology (ASCO)  (5)
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  • American Society of Clinical Oncology (ASCO)  (5)
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  • 1
    Online Resource
    Online Resource
    Tebotelimab, a PD-1/LAG-3 bispecific antibody, in patients with advanced hepatocellular carcinoma who had failed prior targeted therapy and/or immunotherapy: An open-label, single-arm, phase 1/2 dose-escalation and expansion study.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 4_suppl ( 2023-02-01), p. 578-578
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 578-578
    Abstract: 578 Background: Immune checkpoint inhibitors (CPIs) targeting PD-1/PD-L1 have become established treatments for advanced hepatocellular carcinoma (aHCC) but yield low objective response rates (ORRs) in treated patients (pts). Dual inhibition of LAG-3 and PD-1 pathways has demonstrated synergy in activating T-cells and improving immune response. Tebotelimab, also known as MGD013, is a bispecific tetravalent DART molecule that can bind both PD-1 and LAG-3. We initiated an open-label, single-arm, phase 1/2 dose escalation and expansion study to assess the safety and efficacy of tebotelimab in pts with aHCC. Methods: Eligible pts with aHCC who received ≥1 prior systemic treatment with or without prior CPI exposure were enrolled. The dose escalation phase evaluated doses at 120, 240, 400, and 600 mg. Tebotelimab was administered intravenously once every two weeks (Q2W) on days 1 and 15 of each 28-day cycle. The dose expansion phase consisted of one CPI-experienced cohort and one CPI-naïve cohort, both treated at recommended phase 2 dose (RP2D). Primary endpoints were safety for the escalation phase, and safety and ORR per RECIST v1.1 for the expansion phase. Investigator-assessed efficacy results are reported. Results: At data cut-off as of 27 April 2022, 13 pts received tebotelimab in the escalation phase. No dose-limiting toxicity was observed and RP2D was determined as 600 mg Q2W. In the expansion phase, 69 pts (CPI-experienced 33, CPI-naïve 36) were enrolled (median age, 57.0 years; male, 87.0%; ECOG 1, 58.0%; BCLC Stage C, 89.9%; and HBV etiology, 84.1%). Thirteen (18.8%) pts had Grade ≥3 treatment-related adverse events (TRAEs), most commonly hepatic function abnormal (n=3), amylase increased (n=2), and aspartate aminotransferase increased (n=2). Serious TRAEs occurred in nine (13.0%) pts, immune-related adverse events in 30 (43.5%), TRAEs leading to treatment discontinuation in five (7.2%), and treatment-related death in one (1.4%). Of the 30 evaluable pts in the CPI-experienced cohort, one achieved confirmed partial response (PR) and 14 achieved stable disease (SD), with a 3.3% ORR and a 50.0% disease control rate (DCR); of the 30 evaluable pts in the CPI-naïve cohort, four achieved confirmed PR and 10 achieved SD, with a 13.3% ORR and a 46.7% DCR. Median progression-free survival was 2.4 and 3.1 months for CPI-experienced and CPI-naïve cohorts, respectively, with median overall survival not reached in both. Conclusions: Tebotelimab demonstrated a manageable safety profile in pts with aHCC. Antitumor activity, mainly as disease stabilization, was observed in both the CPI-naïve setting and the CPI-experienced setting. No additional clinical trials are planned at this time. Clinical trial information: NCT04212221 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.4_suppl.578
    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
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    Online Resource
  • 2
    Online Resource
    Online Resource
    TALENTACE: A phase III, open-label, randomized study of on-demand transarterial chemoembolization combined with atezolizumab + bevacizumab or on-demand transarterial chemoembolization alone in patients with untreated hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 4_suppl ( 2022-02-01), p. TPS487-TPS487
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 4_suppl ( 2022-02-01), p. TPS487-TPS487
    Abstract: TPS487 Background: In 2020, there were ̃905,000 new cases and ̃830,000 deaths from liver cancer globally, and a respective 410,038 and 391,152 in China (5-year overall survival [OS]: 14.1%). 1,2,3 Hepatocellular carcinoma (HCC) accounts for 75%–85% of liver cancers. 1 Transarterial chemoembolization (TACE) is the preferred treatment for patients with intermediate-stage unresectable HCC (uHCC); however, there are issues with the need for repeated dosing and the heterogenous target population (median OS: 13–43 mo). Treatment with TACE + systemic therapy may improve this. Although several trials reported negative results for TACE + sorafenib (sor) vs TACE alone in patients with uHCC, the TACTICS trial showed improved untreatable (unTACEable) progression-free survival (PFS) (25.2 vs 13.5 mo; P= 0.006). 4 While promising, the unmet need for combination therapies remains. The recent IMbrave150 trial showed significantly improved OS with atezolizumab (atezo) + bevacizumab (bev) vs sor (19.2 vs 13.4 mo; P= 0.0009) in patients with uHCC 5 , making it an attractive option for combination with TACE. Methods: TALENTACE (NCT047126430) is a phase III, open-label, randomized study to evaluate the efficacy and safety of TACE + atezo + bev or TACE alone in patients with uHCC. Key inclusion criteria are ≥18 years old, HCC diagnosis, no prior systemic treatment, no prior locoregional treatment of target lesions, eligible for TACE treatment, tumor max diameter + tumor number ≥6, and not a candidate for curative therapy. Patients with tumors that have macrovascular invasion (MVI) or extrahepatic spread (EHS) are excluded. Patients will be randomized (1:1) to receive TACE + atezo + bev or TACE alone. TACE will be performed by clinical demand; atezo (1200 mg) and bev (15 mg/kg) will be administered by intravenous infusion on Day 1 of each 21-day cycle. Co-primary endpoints are independent review committee-determined TACE-PFS (randomization to unTACEable progression, TACE failure/refractoriness, or death) and OS. Secondary endpoints include investigator-determined TACE-PFS; time to unTACEable progression, progression, MVI, EHS, and MVI/EHS; objective response rate, duration of response, patient reported outcomes, and incidence of adverse events. References: Sung, H., et al. CA Cancer J Clin. 2021;71(3):209–249. World Health Organisation: Globocan 2020 – China Factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf [accessed 1 June 2021] Allemani, C., et al. Lancet. 2018, 391(10125): 1023–1075. Kudo, M., et al. Gut. 2020;69(8):1492–1501. Finn, RS., et al. J Clin Oncol. 2021;39(no. 3_suppl):267–267. Clinical trial information: NCT04712643.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.4_suppl.TPS487
    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
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    Online Resource
  • 3
    Online Resource
    Online Resource
    A phase Ib study of porustobart (HBM4003), an anti-CTLA-4 heavy chain only monoclonal antibody, in combination with toripalimab in patients with hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e16106-e16106
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e16106-e16106
    Abstract: e16106 Background: Porustobart (HBM4003) is a fully human heavy chain only monoclonal antibody (HCAb) targeting CTLA-4. In addition to blocking the CTLA-4 pathway, it has been shown to effectively deplete intratumoral T reg cells in patients due to its engineered enhanced antibody-dependent cellular cytotoxicity (ADCC). Toripalimab is a recombinant, humanized anti-PD-1 monoclonal antibody. Here we reported the results of a phase Ib study that evaluated porustobart plus toripalimab in patients with hepatocellular carcinoma (HCC). Methods: This is a phase Ib dose expansion study (NCT05149027). Patients with advanced HCC (n=28) received porustobart 0.45 mg/kg plus toripalimab 240 mg every three weeks (Q3W) in both Cohort 1 and Cohort 2. Cohort 1 recruited pts who failed previous anti-VEGFR multikinase inhibitor(s) treatment while have not received anti-PD-(L)1 treatment (n=16); Cohort 2 recruited patients who failed previous anti-PD-(L)1 and anti-VEGF(R) treatments (n=12). The primary endpoint was ORR per RECIST 1.1. Results: As of 9 Dec 2022, median follow-up time was 3.6 months (range: 1-7 months). In Cohort 1, ORR and DCR were 46.7% (95%CI: 21.3-73.4) and 73.3% (95%CI: 44.9-92.2) respectively in 15 patients with post-treatment tumor assessments. In Cohort 2, the ORR and DCR were 9.1% (95%CI: 0.2-41.3) and 54.5% (95%CI: 23.4-83.3) respectively in 11 patients with post-treatment tumor assessments. PFS or OS data were not mature by the cut-off date. Treatment-related adverse events (TRAEs) were reported in 89.3% (25/28) patients, and Grade 3 TRAEs were reported in 39.3% (11/28) patients. The most common (≥20%) TRAEs with all grades by pooled term were liver function test abnormal 46.4% (13/28), thrombocytopenia 42.9% (12/28), pyrexia 32.1% (9/28), asthenia 28.6% (8/28), anemia 25% (7/28), decreased appetite 25% (7/28), blood bilirubin increased 21.4% (6/28), leucopenia 21.4% (6/28), lymphopenia 21.4% (6/28), nausea 21.4% (6/28) and neutropenia 21.4% (6/28). TRAEs leading to permanent discontinuation of porustobart were reported in 3 (10.7%) patients. No Grade 4 or Grade 5 TRAE was reported. Porustobart promoted the clearance of T reg cells and the proliferation of CD4 + T cells and CD8 + T cells in peripheral blood that attested to its MOA. Greater effects were observed in Cohort 1. Taken together with the clinical observations these results suggested that PD-(L)1 inhibitor naïve patients have a larger available pool of effectors to induce anti-tumor activity in the presence of effective T reg depletion. No noticeable differences in PK between Cohort 1 and Cohort 2 were observed. Conclusions: Porustobart 0.45 mg/kg in combination with toripalimab 240mg Q3W showed promising anti-tumor activity in patients with advanced HCC, as well as an acceptable safety profile. Clinical trial information: NCT05149027 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e16106
    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
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    Online Resource
  • 4
    Online Resource
    Online Resource
    An open-label, multicenter, adaptive, phase Ib/II study of QL1706 or QL1604 plus bevacizumab as first-line treatment in patients with advanced hepatocellular carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 4077-4077
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4077-4077
    Abstract: 4077 Background: Cancer immunotherapy has expanded the treatment options for advanced HCC (aHCC). Atezolizumab plus bevacizumab is approved as the standard of care for patients (pts) with aHCC. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies (Abs). QL1604 is a humanized mAb against PD-1. The anti-PD-1 Ab of QL1706 has the same protein sequence and was produced by using the same single clone selection method with QL1604. Here we report the safety and efficacy results from a Ph Ib/II study of QL1706 or QL1604 plus bevacizumab (beva) as first-line treatment in pts with aHCC. Methods: Eligible pts had histologically or clinically confirmed HCC; had BCLC stage B/C disease and Child-Pugh class A and B liver function; were systemic therapy naive; and were not suitable for radical surgery and/or locoregional therapy, or progressed after surgery and/or locoregional therapy. This study included 3 parts. Part 1 included a safety run-in phase and an expansion phase. Patients were enrolled to receive QL1706 5 mg/kg plus beva 15 mg/kg Q3W. In part 2, pts were randomized to receive QL1604 200 mg or QL1706 5 mg/kg plus beva 15 mg/kg Q3W. In part 3, pts were enrolled to receive QL1706 7.5 mg/kg plus beva 15 mg/kg Q3W. Initiation of part 3 was to be determined based on factorial analysis on the results from parts 1 and 2. Each treatment cycle lasted for 21 days. Treatment continued until disease progression or other discontinuation events. The primary endpoint was safety. Secondary endpoints included efficacy etc. Results: As of data cutoff (18 Nov 2022), 76 pts were enrolled in parts 1 and 2 (QL1706: 50; QL1604: 26). The baseline characteristics were balanced between the 2 groups. A total of 43 (86%) pts and 23 (88.5%) pts in QL1706 and QL1604 groups experienced TRAEs. For both groups (QL1706 vs QL1604), the most common TRAEs were platelet count decreased (26% vs 23.1%); followed by AST increased (22% vs 19.2%). A total of 17 (34%) pts and 10 (38.5%) pts in QL1706 and QL1604 groups experienced Gr≥3 TRAEs. A total of 25 (50%) pts and 5 (19.2%) pts in QL1706 and QL1604 groups experienced irAEs. The most common irAE in the QL1706 group was rash (16%) (vs 3.8% for QL1604). A total of 8 (16%) pts and 6 (23.1%) pts in QL1706 and QL1604 groups experienced TRSAEs. In the efficacy evaluable population, the ORR was 38.3% (18/47) and 15.4% (4/26) in QL1706 and QL1604 groups. The DCR was 74.5% and 69.2% in QL1706 and QL1604 groups. The mPFS was 6.7 months (95% CI: 3.0-11.4) and 5.4 months (95% CI:2.4-8.5) in QL1706 and QL1604 groups. The mOS was not reached. Conclusions: QL1706 5 mg/kg showed comparable safety profile and numerically higher ORR and longer mPFS vs QL1604 when combined with beva as first-line treatment in pts with aHCC. Ph III head-to-head clinical trial to compare QL1706 or anti-PD-1/PD-L1 Ab plus beva in this population has been planned. Clinical trial information: NCT05603039 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.4077
    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
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    Online Resource
  • 5
    Online Resource
    Online Resource
    A randomized, double-blinded, phase III study of icaritin versus huachashu as the first-line therapy in biomarker-enriched HBV-related advanced hepatocellular carcinoma with poor conditions: Interim analysis result.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 4077-4077
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 4077-4077
    Abstract: 4077 Background: Many advanced hepatocellular carcinoma (aHCC) patients (pts) are often with more complicated clinical conditions such as damaged liver or blood function, poor physical conditions. Those aHCC pts are not suitable for molecular target drug like sorafenib or systemic chemotherapy and no standard or generally accepted treatment. Icaritin, a single molecule ( 〉 98% purity) derived from Epimedii herba (Traditional Chinese herbal medicine), is a novel immune-modulation anti-tumor agent. Preclinical studies demonstrated that Icaritin induced anti-HCC activities through targeting IL-6/JAK//STAT3 pathways and modulating inflammation-immune systems including Th1 cytokines, and down-regulation of alpha-fetoprotein (AFP). Prior phase II study demonstrated favorable overall survival (OS) improvement in aHCC pts with poor conditions and correlated with the combined serum biomarkers. The current phase III study was designed to confirm above clinical benefits and safety of Icaritin in those patients. Methods: An adaptive enrichment design was used in a multicenter randomized, double-blinded study of comparing Icaritin with Huachashu (a TCM formula commonly used in China) as first line therapy for those aHCC pts (NCT03236636). The primary endpoint was overall survival (OS) and secondary endpoints included time-to-progression (TTP), progression-free-survival (PFS), disease control rate (DCR), and safety. The pts were randomized (1:1) to receive either Icaritin at 600mg or Huachashu. Based on prior studies, a composite biomarker score (CBS) of AFP(≥400 ng/mL), TNF-a( 〈 2.5 pg/mL) and IFN-g(≥7.0 pg/mL) was used for pts selection and a CBS score of 2/3 was predefined positive. Patients with CBS-positive were applied in interim analysis according to the protocol and statistical analysis plan (SAP). Results: A total of 283 aHCC pts were enrolled and randomized from Sept. 2017, and 71 enriched pts was CBS-positive with combined risk/poor prognosis factors such as BCLC stage C, HBV infection, and thrombocytopenia etc.. Thirty-three and 38 CBS-positive aHCC pts were treated with Icaritin or Huachashu, respectively. With a median follow-up of 8.1 mo (cutoff date, Dec.30,2020), the treatment outcomes for Icaritin and Huachashu arm showed following, that is mOS, 13.54 vs. 7.06 mo (HR = 0.40, 95%CI 0.21-0.77, p = 0.0046), mTTP, 3.65 vs. 1.84 mo (HR = 0.67, 95%CI, 0.36-1.22), mPFS, 2.79 vs. 1.84 mo (HR = 0.75, 95%CI, 0.43-1.33), and DCR, 48.5% vs. 26.3, respectively. Treatment-related adverse event (AE≥3 grades) observed were 15.2% vs. 31.6%, respectively. Conclusions: Small molecule immunomodulation agent Icaritin could significantly improve the overall survival with favorable safety in a prospectively CBS-enriched HBV-related advanced HCC pts with poor conditions. Clinical trial information: NCT03236636.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.4077
    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
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    Online Resource
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