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Breast CancerPhase 1NCT02838823

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

A Phase 1 study testing humanized anti-PD-1 monoclonal antibody toripalimab in people with Breast Cancer, run by Shanghai Junshi Bioscience Co., Ltd. at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Breast Cancer
What is being tested?
humanized anti-PD-1 monoclonal antibody toripalimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteChina
Study dates
Jul 2016to Sep 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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)
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  • 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.
  • Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

Trial locations and contacts

1 site in 1 country.

China1 site

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

    Beijing, Beijing Municipality, 100071

Other trials in China

About this study

Official title: A Phase I,Open,Mono-center and Dose Escalation Study Investigating Tolerance and Pharmacokinetics of Single and Multiple Doses of Anti-PD-1 Monoclonal Antibody in Patients With Triple-negative Breast Cancer

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.

Read the detailed description

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 previous routine systemic treatment. The study will be conducted in 2 parts: dose escalation and cohort expansion. In the first part, nine patients are injected with different dosage of the humanized anti-PD-1 antibody (1mg/kg or 3mg/kg or 10mg/mg, three patients in one group ) once and observed carefully in the following 4 weeks. If no dose-limiting toxicity (DLT) occurs, then they are injected every 2 weeks until disease progresses or unacceptable toxicity occurs. This part is to confirm DLT, maximum tolerated dose (MTD) and recommended dose (RD). In the second part, 6-12 patients are enrolled in each dosage group and injected with the humanized anti-PD-1 antibody every 2 weeks until disease progresses or unacceptable toxicity occurs. This part is to further analyze safety and efficacy of the humanized anti-PD-1 antibody.

Conditions
Breast Cancer
Being tested
humanized anti-PD-1 monoclonal antibody toripalimab
Keywords
anti-PD-1 monoclonal antibody, triple negative breast cancer, safety
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • humanized anti-PD-1 monoclonal antibody toripalimabBiological

    Also called JS001, TAB001

    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.

Study groups in NCT02838823
Study groupRoleWhat they receive
humanized anti-PD-1 monoclonal antibodyExperimentalhumanized 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.
Receives: Biological: humanized anti-PD-1 monoclonal antibody toripalimab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 1.5 years

Secondary outcomes (17)

  1. PD-1 receptor occupancy of blood

    Measured: 1.5 years

  2. Objective Response Rate (ORR) by irRC and RECIST 1.1

    Measured: 3 years

  3. Duration of Response (DOR) by irRC and RECIST 1.1

    Measured: 3 years

  4. Disease Control Rate (DCR) by irRC and RECIST 1.1

    Measured: 3 years

  5. Time to response (TTR) by irRC and RECIST 1.1

    Measured: 3 years

  6. Progression-free survival(PFS) by irRC and RECIST 1.1

    Measured: 3 years

  7. Overall survival (OS) by irRC and RECIST 1.1

    Measured: 3 years

  8. Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb)

    Measured: 1.5 years

  9. Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb

    Measured: 1.5 years

  10. Area Under the Curve (AUC) after single dose injection of Anti-PD-1 mAb Area Under the Curve [AUC]). Area Under the Curve (AUC) after single dose injection of Recombinant Humanized Anti-PD-1 Monoclonal An

    Measured: 1.5 years

  11. t1/2 after single dose injection of Recombinant Humanized Anti-PD-1 mAb

    Measured: 1.5 years

  12. Plasma clearance (CL) after single dose injection of Anti-PD-1 mAb

    Measured: 1.5 years

  13. Apparent volume of distribution (V) after single dose injection of Anti-PD-1 mAb

    Measured: 1.5 years

  14. Minimum Plasma Concentration (Cmin) of steady state after multiple dose injection of Anti-PD-1 mAb

    Measured: 1.5 years

  15. Average Plasma Concentration (Cav) of steady state after multiple dose injection of Anti-PD-1 mAb

    Measured: 1.5 years

  16. degree of fluctuation (DF) of steady state after multiple dose injection of Anti-PD-1 mAb

    Measured: 1.5 years

  17. Apparent volume of distribution of steady state (Vss) after multiple dose injection of Anti-PD-1 mAb

    Measured: 1.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2016 (estimated)
  2. Study startJul 2016
  3. Primary completionDec 2018
  4. Study completionSep 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02838823
Sponsor's protocol ID
Junshi-JS001-307-I
Status last verified
Oct 2019
First submitted
18 Jul 2016
Last updated
23 Oct 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes

Publications

  • 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.

    PubMed 26947879

  • 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.

    PubMed 26115796

  • 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.

    PubMed 31700871

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing humanized anti-PD-1 monoclonal antibody toripalimab in people with Breast Cancer, run by Shanghai Junshi Bioscience Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 1.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02838823, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2019.

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