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  • American Society of Clinical Oncology (ASCO)  (2)
  • Xu, Aibing  (2)
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  • American Society of Clinical Oncology (ASCO)  (2)
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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
    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
    BibTip Others were also interested in ...
    Online Resource
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