Li Bian1, Huiqiang Zhang1, Tao Wang1, Shaohua Zhang1, Haifeng Song2, Mingli Xu3, Sheng Yao4, Zefei Jiang1. 1. Department of Breast Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China. 2. National Engineering Research Center for Protein Drugs, Beijing Institute of Lifeomics, Beijing 102206, China. 3. Beijing Halma Orient Medicine Technology Co., LTD, Beijing 100088, China. 4. Shanghai Junshi Biosciences Co., LTD, Shanghai 201203, China.
Abstract
BACKGROUND: Triple negative breast cancer (TNBC), as defined by ER, PR and HER2 negative expression in tumor, has limited treatment options beyond conventional chemotherapy. JS001, a humanized IgG4 antibody for PD-1, has demonstrated acceptable safety profile and preliminary anti-tumor activity in solid tumors. METHODS: This phase I open-label study is designed to evaluate the safety, tolerability, and antitumor activity of JS001 in advanced TNBC patients who are refractory to standard systemic therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg Q2W followed by a dose expansion cohort at 3 mg/kg. (Clinical Trial ID: NCT02838823). RESULTS: From August 04, 2016 to October 26, 2017, 20 heavily-pretreated advanced TNBC patients were enrolled into three dose cohorts (6 in 1 mg/kg, 8 in 3 mg/kg and 6 in 10 mg/kg). As of August 30, 2018, no DLT was observed and no MTD was reached. No AEs were grade 4 or 5. The most common treatment related AEs were all grade 1/2. Treatment related grade 3 AEs (15%) included 1 hyponatremia, 1 rash and 1 bronchospasm (infusion related reaction). Among 20 evaluable subjects, the ORR was 5%. One patient in 10 mg/kg group obtained PR, who was PD-L1 strong positive (>50%) in tumor biopsy, with treatment duration of 12.8 months as of data cutoff. As of follow-up on July 15, 2019, the patient continued PR with treatment duration of 24 months and still ongoing. Six patients achieved SD, for a DCR of 35%. The median PFS of all subjects was 1.8 months (95% CI, 1.4 to 4.6). 45% subjects are PD-L1 positive (≥1% cutoff), among whom a 11.1% ORR and a 22.2% DCR were observed. CONCLUSIONS: JS001 exhibited a favorable safety profile in advanced TNBC patients who are refractory to multi-line systemic therapy. JS001 also showed a moderate response in these TNBC patients who had limited treatment options. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Triple negative breast cancer (TNBC), as defined by ER, PR and HER2 negative expression in tumor, has limited treatment options beyond conventional chemotherapy. JS001, a humanized IgG4 antibody for PD-1, has demonstrated acceptable safety profile and preliminary anti-tumor activity in solid tumors. METHODS: This phase I open-label study is designed to evaluate the safety, tolerability, and antitumor activity of JS001 in advanced TNBC patients who are refractory to standard systemic therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg Q2W followed by a dose expansion cohort at 3 mg/kg. (Clinical Trial ID: NCT02838823). RESULTS: From August 04, 2016 to October 26, 2017, 20 heavily-pretreated advanced TNBC patients were enrolled into three dose cohorts (6 in 1 mg/kg, 8 in 3 mg/kg and 6 in 10 mg/kg). As of August 30, 2018, no DLT was observed and no MTD was reached. No AEs were grade 4 or 5. The most common treatment related AEs were all grade 1/2. Treatment related grade 3 AEs (15%) included 1 hyponatremia, 1 rash and 1 bronchospasm (infusion related reaction). Among 20 evaluable subjects, the ORR was 5%. One patient in 10 mg/kg group obtained PR, who was PD-L1 strong positive (>50%) in tumor biopsy, with treatment duration of 12.8 months as of data cutoff. As of follow-up on July 15, 2019, the patient continued PR with treatment duration of 24 months and still ongoing. Six patients achieved SD, for a DCR of 35%. The median PFS of all subjects was 1.8 months (95% CI, 1.4 to 4.6). 45% subjects are PD-L1 positive (≥1% cutoff), among whom a 11.1% ORR and a 22.2% DCR were observed. CONCLUSIONS: JS001 exhibited a favorable safety profile in advanced TNBC patients who are refractory to multi-line systemic therapy. JS001 also showed a moderate response in these TNBC patients who had limited treatment options. 2019 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
JS001; advanced breast cancer; anti-PD-1 mAb; triple negative
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