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Poster display session

3032 - Phase Ia Study of a Humanized Anti-PD-1 Monoclonal Antibody (JS001) in Chinese Patients with Refractory Solid Tumors

Date

10 Sep 2017

Session

Poster display session

Presenters

Feng-Hua Wang

Citation

Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376

Authors

F. Wang1, C. Ren1, Y. Zhang2, S. Yao3, H. Feng3, H. Wu3, H. Song3, R. Zhang4, X. Wei1, X. Xia5, Q. Zhao5, J. Yun6, B. Zou1, M. Qiu1, Z. Wang1, Y. Li1, R. Xu1

Author affiliations

  • 1 Medical Oncology, Cancer Centre Sun Yat-Sen University, 510060 - Guangzhou/CN
  • 2 Gcp, Cancer Centre Sun Yat-Sen University, 510060 - Guangzhou/CN
  • 3 Clinical Trial Research, Shanghai Junshi Bioscience Co.,Ltd, 201203 - Shanghai/CN
  • 4 Imaging, Sun Yat-sen University Cancer Center, 510060 - Guangzhou/CN
  • 5 Experiment, Cancer Centre Sun Yat-Sen University, 510060 - Guangzhou/CN
  • 6 Pathology, Cancer Centre Sun Yat-Sen University, 510060 - Guangzhou/CN
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Resources

Abstract 3032

Background

JS001, a recombinant humanized IgG4 antibody, selectively blocks the interactions of PD-1 with its ligands PD-L1 and PD-L2, and promotes host immune response against Cancer.

Methods

A Phase I open-label study is designed to evaluate the safety and tolerability of JS001 in solid tumor patients who are refractory to standard therapy. The study has a traditional 3 + 3 dose escalation design with planned cohorts at 0.3, 1.0, 3.0, 10 mg/kg Q2W and a fixed-dose 240 mg Q2W followed by a dose expansion.

Results

Enrollment was completed by October 2016 with 25 patients enrolled including 6 esophageal, 5 gastric, 6 nasopharyngeal, 2 pancreatic, 2 head and neck, and 1 Cholangio carcinoma and 3 melanomas. No dose limit toxicity was observed and no maximum tolerated dose was identified. Adverse events (AEs) occurred in 21/25 patients (84%), which were mostly grade 1/2, including fatigue (72%), elevation of liver enzymes (52%), proteinuria (40%), anemia (40%), rash (32%), fever (24%), hyponatremia (24%), hyper- or hypo-thyroidism (20%), and hypokalemia (20%). The emergence of AEs appeared unrelated to dose levels. JS001 PK analysis shows linear dose-dependent exposure with the elimination half-life of 6 to 15 days. Among 13 patients who had underwent at least one scheduled radiographic evaluation, 1 has confirmed complete response (melanoma), 2 have confirmed partial response (1 Head and neck and 1 esophageal), and 2 achieved stable disease. PD-L1 expression by IHC on pretreatment biopsy samples was correlated with the clinical response. Patients with positive PD-L1 staining (> 1%) observed a 30% response rate (n = 10, 1 CR and 2 PR) and a 50% DCR. Whole exon sequencing was performed on selected biopsy samples. Mutations on p53, MDM2, TAP2 et al, might contribute to the favorable response to immunotherapy. Interestingly, a divergent spectrum of mutations from mixed response patients were observed on tumor cells from different metastases, which at the time of biopsy had drastically different clinical response to the treatment.

Conclusions

JS001 demonstrated an acceptable safety profile in solid tumor patients. Additional phase II studies to evaluate the safety and clinical activity of JS001 in selected tumor types are ongoing.

Clinical trial identification

Clinical Trial ID: NCT02857166

Legal entity responsible for the study

Sun Yat-sen University Cancer Center

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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