Cited by 177Cancer Immunotherapy and BiomarkersCutaneous Melanoma Detection and ManagementImmunotherapy and Immune Responses

Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients

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Tang, Bixia, Yan, Xieqiao, Sheng, Xinan, Si, Lu, Cui, Chuanliang, Kong, Yan, Mao, Lili, Lian, Bin +15 more·2019·Journal of Hematology & Oncology

Abstract

BACKGROUND: monoclonal antibody against the programmed death-1 (PD-1) receptor, blocks the interaction of PD-1 with its ligands and promotes T cell activation in preclinical studies. This phase I study is designed to evaluate the safety, tolerability, and clinical activity of JS001 in advanced melanoma or urologic cancer patients who are refractory to standard systemic therapy. PATIENTS AND METHODS: In the dose escalation cohorts, subjects initially received a single-dose, intravenous infusion of JS001, and were followed for 28 days followed by multi-dose infusions every 2 weeks. In the dose expansion cohorts, subjects received multi-dose infusions every 2 weeks. Clinical response was evaluated after each 8-week treatment cycle according to RECIST v1.1 criteria. RESULTS: Thirty-six subjects diagnosed with advanced melanoma (n = 22), urothelial cancer (UC) (n = 8), or renal cell cancer (RCC) (n = 6) were enrolled. Melanoma subjects included 14 acral and 4 mucosal subtypes. JS001 was well tolerated, and no dose-limiting toxicity was observed. By the safety data cutoff date, 100% of subjects had treatment-related adverse events (TRAE) with most adverse events being grade 1 or 2, and ≥ grade 3 TRAEs occurred in 36%. Among all 36 subjects, 1 confirmed complete response (acral melanoma), 7 confirmed partial responses (2 acral melanoma, 1 mucosal melanoma, 2 UC, and 2 RCC), and 10 stable disease were observed, for an objective response rate of 22.2% (95% CI, 10.1 to 39.2), and a disease control rate of 50.0% (95% CI, 32.9 to 67.1). Clinical responses were correlated with PD-L1 expression on tumor cells, the presence of tumor infiltrating lymphocytes (TIL), baseline tumor volume, ECOG performance status, serum LDH levels, high percentage of activated CD8+ T cells and CD3- CD16+ CD54+ NK cells in the peripheral blood as well as tumor mutational burden (TMB). CONCLUSION: JS001 was well tolerated and demonstrated promising anti-tumor activity in UC and RCC as well as in previously underexplored acral and mucosal melanoma subtypes. Subjects with an immune-active profile in the tumor microenvironment or in peripheral blood responded favorably to JS001 treatment. The completion of the current phase I study has led to the initiation of the first prospective anti-PD-1 registration trial in Asia focusing on acral and mucosal melanoma subtypes, representative of the regional disease epidemiology. TRIAL REGISTRATION: Clinical Trial ID: NCT02836795 , registered July 19, 2016, retrospectively registered.

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Authors
Tang, B., Yan, X., Sheng, X., Si, L., Cui, C., Kong, Y., Mao, L., Lian, B., Bai, X., Wang, X., Li, S., Zhou, L., Yu, J., Dai, J., Wang, K., Hu, J., Dong, L., Song, H., Wu, H., Feng, H., Yao, S., Chi, Z., & Guo, J.
Affiliations
  • Peking University Cancer Hospital (CN)
  • Beijing Radiation Center (CN)
  • Junshi Biosciences (China) (CN)
Corresponding author
  • Chi, Zhihong
  • Guo, Jun
Venue
Journal of Hematology & Oncology
Published
2019-01-14
Volume
12
Issue
1
Pages
7-7
ISSN
1756-8722 (ISSN-L)
OpenAlex
W2923110622
Cited by
169
References
32
Citations by year
2026: 5 · 2025: 12 · 2024: 21 · 2023: 30 · 2022: 31 · 2021: 32 · 2020: 26 · 2019: 12
FWCI
11.39
Type
journal article
Language
en
Open access
Locations
  • Journal of Hematology & Oncology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Beijing Municipal Administration of Hospitals Clinical medicine Development of special funding support (ZYLX201603)
  • National Science &Technology Major Project “Key New Drug Creation and Manufacturing Program” (2015ZX09102017)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
anti-PD-1, advanced melanoma, urothelial carcinoma, renal cell carcinoma, immune checkpoint blockade, safety and tolerability, objective response rate, PD-L1 expression, tumor-infiltrating lymphocytes, tumor mutational burden, acral melanoma, mucosal melanoma, predictive biomarkers, dose escalation, dose expansion, natural killer cells
MeSH terms
Progression-Free Survival, Adult, Aged, Antineoplastic Agents, Biopsy, Carcinoma, Renal Cell, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Immunoglobulin G, Infusions, Intravenous, Lymphocyte Activation, Male, Melanoma, Middle Aged, Skin Neoplasms, Biomarkers, Tumor, Urologic Neoplasms, CD8-Positive T-Lymphocytes, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized

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