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  • Mao, Lili  (20)
  • Si, Lu  (20)
  • 2020-2024  (20)
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  • 2020-2024  (20)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-5-20)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-5-20)
    Abstract: Background: The best response and survival outcomes between advanced melanoma patients treated with the anti-PD-1 monotherapy vary greatly, rendering a risk model in need to optimally stratify patients based on their likelihood to benefit from the said treatment. Methods: We performed an ad hoc analysis of 89 advanced melanoma patients treated with the anti-PD-1 monotherapy from two prospective clinical trials at the Peking University Cancer Hospital from April 2016 to May 2018. Clinicodemographical characteristics, baseline and early-on-treatment (median 0.6 months after anti-PD-1 monotherapy initiation) routine laboratory variables, including complete blood count and general chemistry, and best response/survival data were extracted and analyzed in both univariate and multivariate logistic and Cox proportional hazard models. Results: After three rounds of screening, risk factors associated with a poorer PFS included a high pre-treatment neutrophil, derived neutrophil-lymphocyte ratio (dNLR), low pre-treatment hemoglobin, and low early-on-/pre-treatment fold change of eosinophil; those with a poorer OS included a high pre-treatment neutrophil, eosinophil, PLT, early-on/pre-treatment fold change of LDH and neutrophil; and those with a poorer best response included a high pre-treatment NLR and early-on-/pre-treatment LDH fold change. Risk models (scale: low, median-low, median high, and high risk) were established based on these risk factors as dichotomous variables and M stage (with vs. without distant metastasis) for PFS (HR 1.976, 95% CI, 1.507–2.592, P & lt; 0.001), OS (HR 2.348, 95% CI, 1.688–3.266), and non-responder (OR 3.586, 95% CI, 1.668–7.713, P = 0.001), respectively. For patients with low, median-low, median-high, and high risks of developing disease progression (PD), six-month PFS rates were 64.3% (95% CI, 43.5–95.0%), 37.5% (95% CI, 22.4–62.9%), 9.1% (95% CI, 3.1–26.7%), and 0%, respectively. For patients with OS risks of low, median-low, median-high, and high, OS rates at 12 months were 82.5% (95% CI, 63.1–100%), 76.6% (95% CI, 58.4–100%), 42.1% (95% CI, 26.3–67.3%), and 23.9% (95% CI, 11.1–51.3%), respectively. For patients with risks of low, median-low, median-high, and high of being a non-responder, objective response rates were 50.0% (95% CI, 15.7–84.3%), 27.8% (95% CI, 9.7–53.5%), 10.3% (95% CI, 2.9–24.2%), and 0%, respectively. Conclusion: A risk scoring model based on the clinicodemographical characteristics and easily obtainable routinely tested laboratory biomarkers may facilitate the best response and survival outcome prediction and personalized therapeutic decision making for the anti-PD-1 monotherapy treated advanced melanoma patients in Asia.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 2
    In: European Journal of Cancer, Elsevier BV, Vol. 182 ( 2023-03), p. 57-65
    Type of Medium: Online Resource
    ISSN: 0959-8049
    RVK:
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 10040-10040
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 10040-10040
    Abstract: 10040 Background: Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1) with clinical activity in metastasis melanoma but not in its mucosal subtype. In this phase II study (NCT03602547), we investigated the safety and efficacy of CM082 in combination with JS001 in patients (pts) with advanced mucosal melanoma. Methods: The study enrolled pts from 18 to 75 years-old with histologically confirmed metastatic mucosal melanoma, ECOG PS 0-1, no prior systemic anti-cancer treatment. Eligible pts were treated with CM082 tablet (150 or 200 mg once daily) combined with JS001 (240mg every 2 weeks, IV, Q2W) until confirmed disease progression or unacceptable toxicity. Clinical response was evaluated every 8 week. The primary endpoint was overall response rate (ORR) using RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of remission (DOR), and time to first remission (TTR) according to RECIST v1.1 and iRECIST. The safety was also assessed. Results: Between July 2018 and April 12, 2019, 40 pts (19 pts in 150mg group; 21 pts in 200mg group) were enrolled and 38 pts were evaluable for tumor response (150mg n = 18, 200mg n = 20), with 4 (22.2%) confirmed partial response (PR), 6 (33.3%) stable disease (SD) and 8 (44.4%) progression disease (PD) in the 150mg CM082 group; 3 (15%) PRs (including 2 unconfirmed), 10 (50%) SD, and 7 (35%) PD were reported in the 200mg CM082 group. Tumors shrank in 10 pts (56%) in the 150mg group and 10 pts (50%) in the 200mg group. At data cut-off (November 28, 2019), 29 pts had PFS events (150mg n = 12; 200mg n = 17). The median PFS was 5.7 (95% CI 2.0, NE) months and 5.6 (1.9, 7.7) months in the two groups, respectively. The most common treatment-related adverse events (AEs) were grade 1 or 2, including leukopenia, elevated LDH, increased ALT, neutropenia, increased AST, and elevated GGT. Common grade 3 or higher adverse events ( 〉 10%) were increased ALT (12 pts, 30%), increased AST (11 pts, 27.5%), neutropenia (6 pts, 15%) and elevated GGT (6 pts, 15%). Eight pts had 9 serious AEs (SAEs). The study is still ongoing and more data will be presented in the future. Conclusions: PFS benefit was observed in both 150mg and 200mg subgroups. This study demonstrated potentially improved efficacy with predictable toxicities of CM082 in combination with JS001 therapy, which may be an effective treatment option for pts with advanced mucosal melanoma. Clinical trial information: NCT03602547.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e17113-e17113
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17113-e17113
    Abstract: e17113 Background: RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). A phase II clinical study showed that RC48-ADC has a good effect on locally advanced or metastatic urothelial carcinoma with HER2-positive expression that failed standard chemotherapy. In the study, some patients with HER2-postive immunohistochemistry (IHC 2+) but negative FISH test still benefit from the treatment of RC48-ADC.The study was to evaluate the activity and safety of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. Methods: This study is an open-label, single-center, one-arm, non-randomized phase II trial. Eligibility criteria include: histologically confirmed urothelial carcinoma, HER2-negasitive (IHC 0 or 1+), ECOG PS 0-1, treated with ≥1 prior systemic treatment. The patients received RC48-ADC treatment alone (2mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary objectives were activity (ORR) and safety. Progress-free survival, disease control rate and overall survival will also be assessed. Results: As of February 2020, 8 patients were enrolled in the study. The median age was 65 years old. At baseline, most patients (6/8) had visceral metastasis. 6 (75%) patients had received≥2 lines treatment and 4 (50%) patients had prior immune checkpoint inhibitor (CPI) therapy in second line treatment. The objective response rate was 25% (2/8) and the DCR was 75% (6/8). The ORR was 33.3% (2/6) in patients with visceral metastasis and was 50.0% (2/4) in liver metastasis patients. The ORR was 33.3% (2/6) in patients post to ≥ 2 lines of treatment and 25% (1/4) in patients post to immunotherapy. Common treatment-related AEs were AST increase (62.5%), ALT increase (50.0%), nausea (50.0%), leukopenia (37.5%), fatigue (37.5%), vomiting (37.5%), hypoesthesia (25.0%), alopecia (25.0%), and neutropenia (25.0%). Most of these AE were Grade 1 or 2. The AE of Grade 3 was neutropenia (12.5%). The SAE was CPK increased (12.5%). Conclusions: The study showed that RC48-ADC was safety and the ORR was 25% in HER-negative patients with locally advanced or metastatic urothelial carcinoma. Clinical trial information: NCT04073602.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    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. 9530-9530
    Abstract: 9530 Background: CD137 plays the roles as a potent co-stimulator of both adaptive and innate immune cells, being an attractive target for cancer immunotherapy. TWP-101 is a fully humanized agonistic anti-CD137 monoclonal IgG4 antibody, targeting a novel epitope of CD137 with a unique mechanism of actions as a CD137 agonist but not CD137 ligand antagonist. The phase I study of TWP-101 in patient (pt)s with advanced melanoma and urothelial carcinoma was initiated (NCT04871334). Methods: Enrolled pts were advanced melanoma refractory to standard therapy. Dose-escalation includes accelerated titration (0.01 and 0.03mg/kg) and conventional Fibonacci 3+3 dose levels (0.1, 0.3, 1.0 and 3.0 mg/kg). TWP-101 was administered intravenously every Q2W until confirmed progressive disease, unacceptable toxicity or withdrawal of consent. The primary objectives were to define the safety profile, to determine the maximum tolerated dose and RP2D of TWP-101. Secondary objectives were to evaluate pharmacokinetics (PK), immunogenicity and preliminary clinical efficacy. Exploratory objectives were to determine pharmacodynamics (PD) biomarkers. Results: From Feb 2021 to Mar 2022,13 melanoma pts (median age 54 years, range 39-73; 6 men, 7 women; median 2 prior lines of therapy, range 1-6; 12 with prior immunotherapy) were treated. The following five dose levels had been evaluated from 0.01 to 1.0 mg/kg. 3mg/kg dose escalation is ongoing, no MTD has been reached. The median treatment time was 16 wks. (range 2-59). On cutoff date of October 31, 2022, 13 pts discontinued treatment due to progression disease (n = 12) and protocol deviation (n = 1). No DLTs were observed. 9 pts (69.2%) experienced treatment-related adverse events (TRAE). The most common TRAEs (≥10%) were neutropenia (23.1%), leukopenia (15.4%), hypertriglyceridemia (15.4%), anemia (15.4%), hyponatremia (15.4%). 1 pt experienced grade 3-4 TRAEs: hyponatremia, Asthenia and reduced appetite. In all TRAEs, one grade 1 decreased free triiodothyronine and one grade 2 pyrexia were possibly related, and all other TRAEs, including 2 treatment-related SAEs (1 grade 4 hyponatremia and 1 grade 2 subarachnoid hemorrhage), were identified as possibly unrelated. Deaths were due to progression disease (n = 3). Preliminary PK analysis showed dose-proportional kinetics. For 12 evaluable pts, 2 pts achieved PR (16.7%), 5 pts was SD. DCR was 58.3%. Median PFS was 16 wks. (range 16-60), PFS of 2 PR pts was 24 and 60 wks. Conclusions: TWP-101 demonstrated a good safety profile without hepatotoxicity frequently observed with other studied CD137 antibodies. Both favorable tolerability and preliminary antitumor activity warrant further evaluation in pts with advanced melanoma and urothelial carcinoma. Clinical trial information: NCT04871334 .
    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
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 9512-9512
    Abstract: 9512 Background: A phase IB trial had showen promising antitumor activity with toripalimab (T, a PD-1 antibody) plus axitinib (A, a VEGF receptor inhibitor) in treatment-naive unresectable or metastatic mucosal melanoma. Now we conducted a phase II trial to compare the combined treatment with monotherapy. Methods: In this randomized, controlled, phase II trial, patients with pathologically confirmed treatment-naive unresectable or metastatic mucosal melanoma were stratified by PD-L1 expression and randomized 1:1:1 into three groups to receive treatment of T+A (toripalimab 240 mg i.v. every 3 weeks, axitinib 5 mg orally twice a day), T (toripalimab 240 mg i.v. every 3 weeks) or A (axitinib 5 mg orally twice a day). Subjects in T or A who meet the criteria after disease progression may cross over to receive T+A. The primary endpoint was progression-free survival (PFS). Secondary endpoints included Objective response rate (ORR), Duration of response (DOR), overall survival (OS), and safety. The protocol was registered at ClinicalTrials.gov (NCT03941795). This is the interim analysis for efficacy and safety. Results: Between Nov 2019 and Jan 2022, 51 patients were randomized (18 to T+A, 20 to T, and 13 to A due to preliminary efficacy analysis). Anatomic site of head and neck, gastrointestinal, gynecological were 49.0%, 29.4%, 21.6%, respectively. Stage II or III unresectable, M1a, M1b, M1c were 3.9%, 23.5%, 17.6%, 51.0%, respectively. PD-L1 positivity was defined as ≥1% of tumor cells and/or infiltrating immune cells and were identified in 55.6%, 45.0%, 53.8% patients in T+A, T, A group, respectively. 17, 17 and 12 patients could be evaluated in T+A, T and A group, respectively. 24 patients from T or A crossover to T+A group. At a median follow-up of 6.60 months, patients receiving T+A had a higher median PFS (5.83 vs 2.80 vs 1.40 months; HR = 0.538; 95% CI, 0.237 to 1.221; HR = 0.444; 95% CI, 0.182 to 1.081; P = 0.170), ORR (35.3% (29.7% if including crossover patients ) vs 17.6% vs 8.3%), DOR (82.4% (70.3% if including crossover patients) vs 52.9% vs 58.3%) versus T or A group. The median OS was not reached. 80.4% patients experienced treatment-related adverse events (TRAEs). The most common TRAEs were mild (grade 1 or 2) and included diarrhea, proteinuria, hand and foot syndrome, fatigue, elevated transaminase, elevated bilirubin, hypertension, hypo- or hyperthyroidism, and rash. Grade 3 or greater TRAEs occurred in 33.3%, 30.0%, 30.8% of patients in T+A, T, A groups. Conclusions: Toripalimab plus axitinib showed promising antitumor activity versus toripalimab or axitinib alone in patients with treatment-naive unresectable or metastatic mucosal melanoma. Clinical trial information: NCT03941795.
    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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  • 7
    In: JAMA Oncology, American Medical Association (AMA), Vol. 9, No. 8 ( 2023-08-01), p. 1099-
    Abstract: Acral melanoma, known for low tumor mutation burden, responds poorly to immunotherapy. A standard therapy is still lacking. Objective To investigate the activity and safety of camrelizumab (an anti–programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) and temozolomide as first-line treatment in patients with advanced acral melanoma. Design, Setting, and Participants In this single-arm, single-center, phase 2 nonrandomized clinical trial, patients with treatment-naive unresectable stage III or IV acral melanoma were enrolled at Peking University Cancer Hospital and Institute between June 4, 2020, and August 24, 2021. The data cutoff date was April 10, 2022. Interventions Patients received 4-week cycles of intravenous camrelizumab, 200 mg, every 2 weeks; oral apatinib 250 mg, once daily; and intravenous temozolomide, 200 mg/m 2 , once daily on days 1 to 5 until disease progression or unacceptable toxic effects. Main Outcomes and Measures The primary end point was objective response rate as assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (version 1.1). Secondary end points included progression-free survival, time to response, duration of response, disease control rate, overall survival, and safety. Results A total of 50 patients (32 men [64%]; median age, 57 years [IQR, 52-62 years] ) were enrolled and received treatment. The median follow-up duration was 13.4 months (IQR, 9.6-16.2 months). The objective response rate was 64.0% (32 of 50; 95% CI, 49.2%-77.1%). The median time to response and duration of response were 2.7 months (IQR, 0.9-2.9 months) and 17.5 months (95% CI, 12.0 to not reached), respectively. The disease control rate was 88.0% (44 of 50; 95% CI, 75.7%-95.5%). The estimated median progression-free survival was 18.4 months (95% CI, 10.6 to not reached). The median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse events were increased gamma-glutamyltransferase levels (15 [30%]), decreased neutrophil count (11 [22%] ), increased conjugated bilirubin levels (10 [20%]), and increased aspartate aminotransferase levels (10 [20%] ). No treatment-related deaths occurred. Conclusions and Relevance The findings of this nonrandomized clinical trial suggest that camrelizumab plus apatinib and temozolomide may be a potential first-line treatment option for patients with advanced acral melanoma, which warrants further validation in a randomized clinical trial. Trial Registration ClinicalTrials.gov Identifier: NCT04397770
    Type of Medium: Online Resource
    ISSN: 2374-2437
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 8
    In: Urologic Oncology: Seminars and Original Investigations, Elsevier BV, Vol. 39, No. 1 ( 2021-01), p. 75.e1-75.e8
    Type of Medium: Online Resource
    ISSN: 1078-1439
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2011021-2
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  • 9
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 11, No. 1 ( 2023-01), p. e005937-
    Abstract: Accumulating data suggest that mucosal melanoma, well known for its poor response to immune checkpoint blockade (ICB) and abysmal prognosis, is a heterogeneous subtype of melanoma with distinct genomic and clinical characteristics between different anatomic locations of the primary lesions. Primary malignant melanoma of the esophagus (PMME) is a rare, highly aggressive disease with a poorer prognosis compared with that of non-esophageal mucosal melanoma (NEMM). In this study, we retrospectively analyzed the efficacy of anti-programmed death (PD)-1 in patients with PMME and explored its molecular basis. Methods The response and survival of patients with PMME and NEMM under anti-PD-1 monotherapy were retrospectively analyzed. To explore the molecular mechanisms of the difference in therapeutic efficacy between PMME and NEMM, we performed genomic analysis, bulk RNA sequencing, and multiplex immunohistochemistry staining. Results We found that PMME (n=28) responded better to anti-PD-1 treatment than NEMM (n=64), with a significantly higher objective response rate (33.3% (95% CI 14.3% to 52.3%) vs 6.6% (95% CI 0.2% to 12.9%)) and disease control rate (74.1% (95% CI 56.4% to 91.7%) vs 37.7% (95% CI 25.2% to 50.2%)). Genomic sequencing analysis revealed that the genomic aberration landscape of PMME predominated in classical cancer driver genes, with approximately half of PMME cases harboring mutations in BRAF , N/KRAS , and NF1 . In contrast, most NEMM cases were triple wild-type. Transcriptome analysis revealed that, compared with NEMM, PMME displayed more significant proliferation and inflammatory features with higher expression of genes related to antigen presentation and differentiation, and a less immunosuppressive signature with lower expression of inhibitory immune checkpoints and dedifferentiation-related genes. The multiplex immunohistochemical analysis also demonstrated higher CD8 + T-cell infiltration in PMME than in NEMM. Conclusions PMME is an outlier of mucosal melanoma showing a malicious phenotype but a particularly high response rate to ICB because of its distinct molecular characteristics. Patient stratification based on anatomic origin can facilitate clinical decision-making in patients with mucosal melanoma following the verification of our results in future prospective studies.
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2719863-7
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  • 10
    In: Translational Oncology, Elsevier BV, Vol. 14, No. 1 ( 2021-01), p. 100949-
    Type of Medium: Online Resource
    ISSN: 1936-5233
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2443840-6
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