Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients
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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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Antibodies blocking PD-1 or PD-L1 have been approved to treat various solid and hematologic malignancies.
“At present, antibodies blocking PD-1 or its ligand PD-L1 have been approved to treat various solid and hematologic malignancies (Table 1) [7–12].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [12]
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Self-citation
- 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
- ORCID
- Venue
- Journal of Hematology & Oncology
- Published
- 2019-01-14
- Volume
- 12
- Issue
- 1
- Pages
- 7-7
- ISSN
- 1756-8722 (ISSN-L)
- PMC
- PMC6332582
- 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
- gold
- doi.org
- Licence
- 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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