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  • 1
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    Disitamab vedotin, a novel humanized anti-HER2 antibody-drug conjugate (ADC), combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma: An open-label phase 1b/2 study.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 4566-4566
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 4566-4566
    Abstract: 4566 Background: Disitamab vedotin has shown promising data across a spectrum of HER2 expression in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who progressed on chemotherapy. This study was conducted to evaluate the safety and efficacy of disitamab vedotin plus anti-PD-1 antibody in advanced urothelial carcinoma. Methods: This is an open-label, multicenter, phase 1b/2 trial to evaluate the safety and activity of RC48-ADC combined with toripalimab, a humanized immunoglobin G 4 monoclonal antibody against PD-1 in mUC. Patients received RC48-ADC at 1.5 or 2 mg/kg, in combination with 3mg/kg toripalimab every two weeks in a dose-escalation and expansion cohort until confirmed disease progression assessed by the investigators, unacceptable toxicity, or voluntary withdrawal. The primary endpoint was safety; secondary endpoints included efficacy and tumor tissue biomarkers. Results: Forty-one la/mUC patients were enrolled (22 males; median age 66 y [42-76]; 61% treatment-naïve). 54% of patients had visceral metastases (mets), including 24% with liver mets. The primary site was in upper tract UC in 54%. HER2 expression IHC 2+ or 3+ was in 59% patients, and PD-L1 positive in 32%. No dose-limiting toxicity was observed and the recommended dose was RC48-ADC 2mg/kg plus toripalimab 3mg/kg every two weeks. By the cutoff date of 18 November 2022, the confirmed ORR was 73.2% (95%CI: 57.1, 85.8), including 9.8% CR. The ORR was 76.0% for treatment-naïve patients. In HER2 IHC 3+/2+, IHC 1+, and IHC 0 subgroups, the ORR was 83.3%, 64.3%, and 33.3%, respectively. The ORR was 61.5% and 78.6% in PD-L1 positive and negative subgroups. DCR was 90.2% (95% CI, 76.9–97.3), with a median progression-free survival (PFS) of 9.2 months (95%CI: 5.7-10.3) and 2-year overall survival (OS) rate of 63.2%. All patients experienced treatment-related adverse events (TRAEs). The most common TRAEs were AST/ALT increase (68.3%), peripheral sensory neuropathy (61.0%), asthenia (61.0%), γ-glutamyl transferase increase (56.1%), hypertriglyceridemia (53.7%), and appetite decrease (51.2%). Grade 3 or greater TRAEs occurred in 43.9% of patients. Twenty-three patients (56.1%) had immune-related AEs (14.6% ≥ G3), including immune-related skin reactions, hyperglycemia, pneumonitis, hepatitis, and myositis. Conclusions: RC48-ADC in combination with toripalimab demonstrated promising efficacy in patients with la/mUC and a manageable safety profile. A phase 3 study is currently ongoing to compare the safety and efficacy of this regimen with standard of care. Clinical trial information: NCT04264936 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.4566
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Genetic Aberrations in the CDK4 Pathway Are Associated with Innate Resistance to PD-1 Blockade in Chinese Patients with Non-Cutaneous Melanoma
    American Association for Cancer Research (AACR) ; 2019
    In:  Clinical Cancer Research Vol. 25, No. 21 ( 2019-11-01), p. 6511-6523
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 21 ( 2019-11-01), p. 6511-6523
    Abstract: PD-1 checkpoint blockade immunotherapy induces long and durable response in patients with advanced melanoma. However, only a subset of patients with melanoma benefit from this approach. The mechanism triggering the innate resistance of anti–PD-1 therapy remains unclear. Experimental Design: Whole-exome sequencing (WES) and RNA sequencing (RNA-Seq) analyses were performed in a training cohort (n = 31) using baseline tumor biopsies of patients with advanced melanoma treated with the anti–PD-1 antibody. Copy-number variations (CNVs) for the genes CDK4, CCND1, and CDKN2A were assayed using a TaqMan copy-number assay in a validation cohort (n = 85). The effect of CDK4/6 inhibitors combined with anti–PD-1 antibody monotherapy was evaluated in PD-1–humanized mouse (C57BL/6-hPD-1) and humanized immune system (HIS) patient-derived xenograft (PDX) models. Results: WES revealed several significant gene copy-number gains in the patients of no clinical benefit cohort, such as 12q14.1 loci, which harbor CDK4. The association between CDK4 gain and innate resistance to anti–PD-1 therapy was validated in 85 patients with melanoma (P & lt; 0.05). RNA-Seq analysis of CDK4-normal cell lines and CDK4-normal tumors showed altered transcriptional output in TNFα signaling via NF-κB, inflammatory response, and IFNγ response gene set. In addition, CDK4/6 inhibitor (palbociclib) treatment increased PD-L1 protein levels and enhanced efficacy (P & lt; 0.05) in the C57BL/6-hPD-1 melanoma cell and the HIS PDX model. Conclusions: In summary, we discovered that genetic aberrations in the CDK4 pathway are associated with innate resistance to anti–PD-1 therapy in patients with advanced melanoma. Moreover, our study provides a strong rationale for combining CDK4/6 inhibitors with anti–PD-1 antibody for the treatment of advanced melanomas.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-19-0475
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 3
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    The Clinicopathological and Survival Profiles Comparison Across Primary Sites in Acral Melanoma
    Springer Science and Business Media LLC ; 2020
    In:  Annals of Surgical Oncology Vol. 27, No. 9 ( 2020-09), p. 3478-3485
    Details
    In: Annals of Surgical Oncology, Springer Science and Business Media LLC, Vol. 27, No. 9 ( 2020-09), p. 3478-3485
    Abstract: The clinicopathological and survival profiles across primary sites in acral melanoma (AM) are still controversial and unclear. Methods This is a multi-center retrospective study. Clinicopathological data of AM patients diagnosed between 1 January 2000 and 31 December 2017 from 6 large tertiary hospitals in China were extracted. Chi square tests were used to compare basic characteristics between primary sites of sole, palm and nail bed. Melanoma-specific survival (MSS) differences based on primary sites were compared by log-rank tests and multivariate Cox regressions were used to identify prognostic factors for MSS. Results In total, 1157 AM patients were included. The sole group had a more advanced initial stage, deeper Breslow thickness, higher recurrence rate and distant metastases risk (all P   〈  0.05). The proportion of age 〈  65 years and ulceration were statistically lower in nail bed and palm groups, respectively. A total of 294 patients underwent sentinel lymph node biopsy and rates of positive SLN status had no statistical difference across primary sites. Among 701 patients with genetic profiles, the mutational frequency of BRAF, C-KIT, and PDGFRA were similar except for NRAS (higher in sole group, P  = 0.0102). The median MSS of sole, nail bed and palm patients were 65.0 months, 112.0 months, and not reached, respectively (log-rank P  = 0.0053). In multivariate analyses, primary site, initial stage, ulceration and recurrence were the prognostic factors for MSS in overall population, but the statistical significance varied over primary sites. Conclusions Substantial clinicopathological and survival heterogeneities exist across different primary sites in the AM population. Sole melanoma has worse prognosis compared with palm and nail bed subtypes.
    Type of Medium: Online Resource
    ISSN: 1068-9265 , 1534-4681
    URL: Article
    DOI: 10.1245/s10434-020-08418-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2074021-9
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  • 4
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    Study RC48-C014: Preliminary results of RC48-ADC combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 515-515
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 515-515
    Abstract: 515 Background: RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC), which showed promising data in HER2-positive and even negative patients (pts) with metastatic urothelial carcinoma (mUC). Toripalimab is an anti-PD-1 antibody with a durable antitumor effect for mUC. The combination may have a synergistic antitumor effect. Initial RC48-C014 data was previously presented (ASCO 2021); here we reported an update on safety and ORR. Methods: In dose-escalation cohort, pts received 1.5 or 2 mg/kg RC48-ADC + 3mg/kg toripalimab with the traditional 3+3 escalation design. In the expansion cohort, patients received the recommended dose of RC48-ADC + toripalimab every 2 weeks. The primary endpoints were safety/tolerability and recommended RC48-ADC dose; secondary endpoints included pharmacokinetics, ORR per RECIST 1.1, PFS, and OS, stratified by HER2 and PD-L1 expression. Results: As of 23 Sep 2021 (data cutoff), 32 mUC pts (18 males; median age 67 y [52-76]) were enrolled since 20 Aug 2020. Fifty-three percent pts were systemic treatment naïve in the locally advanced or metastatic setting. The primary site was in upper tract UC in 56%; 53% had visceral metastases (mets), including 28% with liver mets; HER2 expression was positive (IHC 3+ or 2+ ISH+) in 19% pts, and PD-L1 CPS≥1 in 56%. No dose-limiting toxicity was reported, and the recommended dose for RC48-ADC was 2mg/kg. At data cutoff, confirmed investigator-assessed ORR was 75% (95%CI: 50.9, 91.3), including 15% CRs; DCR was 95% (95%CI: 75.1, 99.9). The ORR for 1L previously untreated mUC pts was 80% and 75% for pts with liver mets. The ORR was 100% for pts with HER2 (3+), 77.8% for HER2 (2+), 66.7% for HER2 (1+), and 50% for HER2 (0) respectively. The ORR was 97.1% in pts with PD-L1 CPS≥1 and 50% in CPS 〈 1. Follow-up continues for PFS and OS. Most common treatment-related AEs were anorexia (72%), asthenia (56%, 8%≥G3), aminotransferase level increased (56%, 4%≥G3), peripheral sensory neuropathy (56%), alopecia (52%), nausea (36%), and anemia (32%). The most common immune-related AE was pneumonitis (20%). Conclusions: RC48-ADC in combination with toripalimab demonstrated promising efficacy in pts with mUC and a manageable safety profile. Further evaluation of RC48 + toripalimab in mUC is ongoing. Clinical trial information: NCT04264936.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.515
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Preliminary results of a phase Ib/II combination study of RC48-ADC, a novel humanized anti-HER2 antibody-drug conjugate (ADC) with toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) in patients with locally advanced or metastatic urothelial carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 4518-4518
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 4518-4518
    Abstract: 4518 Background: RC48-ADC has shown promising data in HER2-positive and even negative patients with metastatic urothelial carcinoma (mUC) who failed with platinum-based chemotherapy. RC48-ADC combined with anti-PD-1 antibody may have a synergistic antitumor effect. Methods: This is an open-label, multicenter, phase 1b/II trial to evaluate the safety and activity of RC48 combined with toripalimab in mUC. Patients received RC48-ADC at 1.5 or 2 mg/kg, in combination with 3mg/kg toripalimab every two weeks in a dose-escalation and expansion cohort until confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. The key primary endpoint was safety; secondary endpoints included efficacy and tumor tissue biomarkers. Results: As of 17 Jan 2022 (data cutoff), 41 la/mUC pts (19 males; median age 66 y [42-76]) were enrolled since 20 Aug 2020. 61% patients were systemic treatment naïve, and 54% had visceral metastases (mets), including 24% with liver mets. The primary site was in upper tract UC in 54%. HER2 expression was positive (IHC 2+ or 3+) in 59% patients, and PD-L1 positive (CPS ≥ 10) in 32%. No dose-limiting toxicity was observed. The recommended dose was RC48-ADC 2mg/kg + toripalimab 3mg/kg every 2 weeks. With a median follow-up of 8.0 mos, 36 patients had at least one tumor assessment, the best ORR was 83.3%, and the confirmed ORR was 76.7% (95%CI: 57.7, 90.1), including 10% CR. The cORR was 82.4% for 1L previously untreated mUC patients, 100% for patients with HER2 IHC (2+ or 3+) & PD-L1 (+), 92.3% for HER2 (2+ or 3+) & PD-L1 (-), 50% for HER2 (0 or 1+) & PD-L1 (+), and 50% HER2 (0 or 1+) & PD-L1 (-). DCR was 96.7% (95%CI: 82.8, 99.9). The median PFS was immature and 9.2 mos (95%CI: 5.49, 10.32) by the time and the median OS was not reached. The most common treatment-related AEs were ALT/AST increase (65.9%), peripheral sensory neuropathy (58.5%), appetite decrease (56.1%), asthenia (56.1%), hypertriglyceridemia (48.8%). Grade ≥3 TRAEs included γ-glutamyl transferase increase (12.2%), ALT/AST increase (7.3%), asthenia (7.3%), hypertriglyceridemia (4.9%), and neutropenia (4.9%). 9 pts had irAEs (22.0%, 7.3% ≥ G3), including immune-related pneumonitis, hepatitis, and myositis. Conclusions: RC48-ADC in combination with toripalimab demonstrated promising efficacy in patients with mUC and a manageable safety profile. A randomized study of RC48-ADC and toripalimab vs. platinum-based chemotherapy in previously untreated la/mUC patients is ongoing. Clinical trial information: NCT04264936. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.4518
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 6
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    A phase Ib study of JS001, a humanized IgG4 mAb against programmed death-1 (PD-1) combination with axitinib in patients with metastatic mucosal melanoma.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 9528-9528
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 9528-9528
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.9528
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
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  • 7
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    Mucosal melanoma staging and classification: Firstly established.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e21008-e21008
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e21008-e21008
    Abstract: e21008 Background: Mucosal melanomas (MM) have a significantly worse survival outcome than cutaneous melanoma. The current staging rules for cutaneous melanoma do not apply to mucosal melanoma. Our previous studies have demonstrated mucosal melanomas arising from different anatomic sites can be staged and treated as a single disease entity. We are recommending a new evidence-based staging system for mucosal melanoma. Methods: The mucosal melanoma staging recommendations were made on the basis of a multivariate analysis of 543 patients with stages I, II, and III melanoma and 547 patients with stage IV melanoma to clarify TNM classifications and stage grouping criteria. Results: New staging definitions include the following: (1) in patients with localized melanoma, the depth of tumor invasion of the primary melanomas is the most dominant prognostic factor: T1 for tumor invading mucosa or submucosa; T2 for tumor invading the muscularis propria; T3 for tumor invading adventitia; T4 for tumor invading adjacent structures; (2) The dominant prognostic factor for regional nodal metastases is the number of metastatic nodes: N1 for 1 regional metastatic node; N2 for 2 or more regional metastatic nodes; (3) On the basis of a multivariate analysis of patients with distant metastases, the dominant component in defining the M category is the site of distant metastases (M1:lung only vs. M2:liver only vs. M3:brain only vs. M4:all other visceral metastatic sites). An elevated serum lactate dehydrogenase level would be designated in parenthesis. The staging grouping of mucosal melanoma can be defined as follow: (1) stage I: T1N0M0; (2) Stage II:T2-4N0M0; (3) Stage IIIA: T1-4N1M0, Stage IIIB: T1-4N2M0; (4) Stage IV: anyTanyNM1-4. Conclusions: Using an evidence-based approach, the proposed staging system of mucosal melanoma is the first to be established that reflects our improved understanding of this disease.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e21008
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 8
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    Systemic therapy in patients with metastatic Xp11.2 translocation renal cell carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 341-341
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 341-341
    Abstract: 341 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 tRCC was found in 45 patients. The median PFS and median OS was 7.4 months (4.5 - 8.8) and 17.9 months (12.4 - 24.4), respectively. First-line treatment mainly included sunitinib (n = 14), sorafenib (n = 15), axitinib (n = 6), and pazopanib (n = 5), and the median PFS of these regimens were 7.4 months, 5.4 months, 9.4 months, 8.9 months, respectively. Two patients who received Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) plus immune checkpoint inhibitor (ICI) as first line therapy had a PFS of more than 16.6 months and more than 25.6 months, respectively. Twenty-four patients received subsequent therapies, which included VEGFR-TKI/ICI, axitinib and mTOR inhibitor, the median PFS for these regimens was 8.5, 7.2 and 2.0 months, respectively. Patients with serous cavity effusion or IMDC poor risk groups had significantly shorter median PFS and median OS. Conclusions: Metastatic Xp11.2 tRCC is an aggressive disease. VEGFR-TKI agents appeared to demonstrate some efficacy, VEGFR-TKI/ICI combination might be a useful tool for the treatment of metastatic Xp11.2 tRCC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.341
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 9
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    Phase II clinical trial of camrelizumab combined with famitinib for advanced acral and mucosal melanoma.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 9550-9550
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9550-9550
    Abstract: 9550 Background: Acral and mucosal melanoma were rarely seen in Caucasians but common in Asians. Previous studies revealed that acral and mucosal melanoma are more aggressive than cutaneous melanoma with a high unmet need for effective treatments. Camrelizumab plus anti-angiogenic agents have shown promising antitumor activity in previously untreated melanoma. Famitinib, a selective multiple-target tyrosine kinase inhibitor that exhibits both anti-angiogenesis and antiproliferative effects via targeting VEGFR-2, PDGFR, c-kit, FGFR and so on, combined with camrelizumab had been proven effective in multiple cancers. This study aimed to assess the antitumor activity and safety of camrelizumab plus famitinib in both immunotherapy naïve and experienced advanced mucosal or acral melanoma. Methods: This single-center, open-label phase II study recruited patients (pts) with advanced acral and mucosal melanoma. Pts who were immune checkpoint inhibitors (ICI) treatment naïve were in cohort 1, while pts experienced ICI in cohort 2. In both cohorts, pts received camrelizumab (200 mg i.v. q3w) and famitinib (20 mg po qd) until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) per RECIST1.1. Secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. This analysis focused on cohort 2. Results: As of January 12, 2023, 18 pts (9 mucosal and 9 acral histology subtypes) were enrolled in cohort 2. The median age of all pts was 58 yrs (ranged 38-71 yrs); 9 pts (50.0%) were female; prevalence of mutations: BRAF (11.1%), C-KIT or NRAS (16.7% each); 38.9% received ≥2 prior treatments. All pts progressed after anti-PD-1/L1 monotherapy (27.8%) or combinational therapy (66.7%), except one progressed after 4-1BB mAb monotherapy. The combination drugs included anti-LAG-3/CTLA-4 antibodies (38.9%), oncolytic viruses (11.1%), c-kit inhibitors, chemotherapy and anti-angiogenic agents (5.6% each). The median follow-up was 7.3 months (ranged 4.6-14.7 months). At the data cutoff, 5 pts remained on treatment. 17 pts were evaluable. The ORR and DCR were 17.6% and 64.7%, including two pts with confirmed PR, and one with unconfirmed PR, all of which were acral subtype. The median PFS was 6.0 months. The median OS was not reached. Of 18 pts, the incidence of treatment-related adverse events (TRAEs) was 88.9%. The most common grade 3 TRAEs was neutrophil count decreased (11.1%). No grade 4 TRAEs and no treatment-related deaths occurred. Conclusions: Camrelizumab plus famitinib showed promising antitumor activity in ICI-experienced advanced acral and mucosal melanoma pts, and was generally well tolerated. Clinical trial information: NCT05051865 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.9550
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 10
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    Toripalimab plus axitinib versus toripalimab or axitinib alone in patients with treatment-naive unresectable or metastatic mucosal melanoma: Interim results from a randomized, controlled, phase II trial.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 9512-9512
    Details
    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
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.9512
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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