Safety and Tolerability of Recombinant Humanized Anti-PD-1 Monoclonal Antibody for Patients With Advanced Breast Cancer

NCT02838823 | Completed Phase 1 DMC

• 1 other identifier: Junshi-JS001-307-I
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a mono-center, open-label, phase 1 study evaluating the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with triple negative breast cancer who have failed in routine systemic treatment. The study will be conducted in 2 parts: dose escalation and cohort expansion to investigate tolerability and efficacy.

Conditions

Breast Cancer

Keywords

anti-PD-1 monoclonal antibody; triple negative breast cancer; safety

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  1.5 years

Secondary Outcomes (17)

• PD-1 receptor occupancy of blood

  1.5 years

• Objective Response Rate (ORR) by irRC and RECIST 1.1

  3 years

• Duration of Response (DOR) by irRC and RECIST 1.1

  3 years

• Disease Control Rate (DCR) by irRC and RECIST 1.1

  3 years

• Time to response (TTR) by irRC and RECIST 1.1

  3 years

Other Outcomes (6)

• correlation analysis of PD-L1 expression of tumor and ORR

  3 years

• correlation analysis of PD-L1 expression of tumor and DOR

  3 years

• correlation analysis of PD-L1 expression of tumor and DCR

  3 years

Study Arms (1)

humanized anti-PD-1 monoclonal antibody

EXPERIMENTAL

humanized anti-PD-1 monoclonal antibody is to be injected intravenously 1mg/kg or 3mg/kg or 10mg/kg until disease progresses or unacceptable tolerability occurs.

Biological: humanized anti-PD-1 monoclonal antibody toripalimab

Interventions

humanized anti-PD-1 monoclonal antibody toripalimab BIOLOGICAL

humanized anti-PD-1 monoclonal antibody (JS001) is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activation of lymphocytes and elimination of malignancy theoretically.

Also known as: JS001, TAB001

humanized anti-PD-1 monoclonal antibody

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and Female aged 18 to 70 years are eligible;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Histologic diagnosis of triple negative breast cancer. Have failed at least 1 prior routine regimen for metastatic disease, or failed to tolerate the toxicity, or lack of any routine regimens.
• Histologically confirmed estrogen receptor negative (ER-) and progesterone receptor negative (PR-), human epidermal growth factor receptor 2 negative
• Providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes);
• At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded) (routine CT scan \>=20mm, spiral CT scan \>=10mm, no prior radiation to measurable lesions) Predicted survival \>=6 months;
• Brain or meningeal metastases must be disposed with surgery or radiation, and be stable clinically for at least 8 weeks (prior systemic steroids was allowed, but concurrent administration of systemic steroids with the study drug is excluded).
• Screening laboratory values must meet the following criteria（within past 14 days）:
• hemoglobin ≥ 9.0 g/dL neutrophils ≥ 1500 cells/ µL platelets ≥ 100 x 10\^3/ µL total bilirubin ≤ 1.5 x upper limit of normal (ULN) aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis serum creatinine ≤1╳ULN，creatinine clearance \>50ml/min (Cockcroft-Gault equation)
• Without systemic steroids within past 4 weeks
• Males or female of childbearing potential must: agree to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 12 months after the last dose of study drug.
• Must have read, understood, and provided written informed consent voluntarily. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

You may not qualify if:

• Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Ab or its components.
• Prior treatment with mAb within past 3 months (locally administration excluded)
• Prior antitumor therapy (including corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment;
• Pregnant or nursing
• Abnormal Blood coagulation
• Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (\>500IU/ml)
• History with pulmonary tuberculosis;
• Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism.
• Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure \> class II NYHA, heart block \>II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm).
• Evidence with CNS disease.
• Prior treatment with bone marrow stimulating factors，such as CSF (colony stimulating factor), EPO (erythropoietin), within past 1 weeks
• Prior live vaccine therapy within past 4 weeks.
• Prior major surgery within past 4 weeks (diagnostic surgery excluded).
• Psychiatric medicines abuse without withdrawal, or history of psychiatric illness.
• Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix.

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (1)

Gastrointestinal Oncology Department, Affiliated Cancer Center of Academy of Military Medical Sciences

Beijing, Beijing Municipality, 100071, China

Location

Related Publications (3)

• Chen R, Peng PC, Wen B, Li FY, Xie S, Chen G, Lu J, Peng Z, Tang SB, Liang YM, Deng X. Anti-Programmed Cell Death (PD)-1 Immunotherapy for Malignant Tumor: A Systematic Review and Meta-Analysis. Transl Oncol. 2016 Feb;9(1):32-40. doi: 10.1016/j.tranon.2015.11.010.

  PMID: 26947879 BACKGROUND

• Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, Hodi FS, Schachter J, Pavlick AC, Lewis KD, Cranmer LD, Blank CU, O'Day SJ, Ascierto PA, Salama AK, Margolin KA, Loquai C, Eigentler TK, Gangadhar TC, Carlino MS, Agarwala SS, Moschos SJ, Sosman JA, Goldinger SM, Shapira-Frommer R, Gonzalez R, Kirkwood JM, Wolchok JD, Eggermont A, Li XN, Zhou W, Zernhelt AM, Lis J, Ebbinghaus S, Kang SP, Daud A. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):908-18. doi: 10.1016/S1470-2045(15)00083-2. Epub 2015 Jun 23.

  PMID: 26115796 BACKGROUND

• Bian L, Zhang H, Wang T, Zhang S, Song H, Xu M, Yao S, Jiang Z. JS001, an anti-PD-1 mAb for advanced triple negative breast cancer patients after multi-line systemic therapy in a phase I trial. Ann Transl Med. 2019 Sep;7(18):435. doi: 10.21037/atm.2019.09.08.

  PMID: 31700871 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Zefei Jiang

  Gastrointestinal Oncology Department, Affiliated Cancer Center of Academy of Military Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2016
• First Posted: July 20, 2016
• Study Start: July 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: September 1, 2019
• Last Updated: October 23, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)