Study of JS001 in Patients With Advanced Neuroendocrine Tumors

NCT03167853 | Completed Phase 1 DMC

• 1 other identifier: HMO-JS001-Ib-NEC-02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, open-label, phase Ib study evaluating safety and efficacy of the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with neuroendocrine tumors who have failed in previous systemic treatment. 40 patients are enrolled and injected with the humanized anti-PD-1 antibody 3mg/mg every 2 weeks until disease progresses or unacceptable toxicity.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  CT/MRI will be performed every 2 cycles of treatment by RECIST 1.1(each cycle is 21 days))

  From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcomes (8)

• Duration of response (DOR)

  baseline, every 8 weeks up to 1 year after last patient first treatment

• Progression-free survival

  baseline, every 8 weeks up to 1 year after last patient first treatment

• Overall survival

  Every 3 months after last visit up to 2 year after last patient first treatment

• Immune Response Criteria by irRECIST (immune response duration of response)

  baseline, every 8 weeks up to 1 year after last patient first treatment

• Immune Response Criteria by irRECIST (immune response overall response rate)

  baseline, every 8 weeks up to 1 year after last patient first treatment

Study Arms (1)

humanized anti-PD-1 monoclonal antibody

EXPERIMENTAL

humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg per 2 weeks until disease progresses or unacceptable tolerability occurs.

Biological: humanized anti-PD-1 monoclonal antibody

Interventions

humanized anti-PD-1 monoclonal antibody BIOLOGICAL

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

Also known as: JS001

humanized anti-PD-1 monoclonal antibody

Eligibility Criteria

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

You may qualify if:

• 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.
• Male and Female aged 18 and older are eligible;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
• Histologic diagnosis of locally advanced or metastatic nonfunctional neuroendocrine tumors, including well-differentiated neuroendocrine tumors and pooly-differentiated neuroendocrine carcinoma;
• Ki-67 index ≥10%;
• Unresectable;
• Radiographic evidence of disease rogression by RECIST criteria on or after last anti-cancer therapy within 6 months;
• Prior treatment meeting the following criteria:
• Patients with pooly-differentiated neuroendocrine carcinomas must have received platinum based lineds of chemotherapy;
• Patients with well-differentiated neuroendocrine tumors must have received at least one systemic treatment, including somatostatin analogs, mTOR inhibitors, anti-angiogentic agents and chemotherapy;
• Providing with tumor specimen (for testing the expression of PD L1 and the infiltrating lymphocytes);
• Predicted survival \>=3 months;
• 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);
• 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 (CockcroftGault equation) PT/INR, aPTT≤1.5 x ULN;
• Without systemic steroids within past 4 weeks;

You may not qualify if:

• Prior treatment with antiPD1/PDL1/PDL2 antibody;
• Hypersensitivity to recombinant humanized antiPD1 monoclonal Ab or its components;
• Prior treatment with mAb within past 4 weeks;
• 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;
• Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (\>500IU/ml);
• History with 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 active CNS disease;
• Meningeal carcinomatosis;
• Prior treatment with bone marrow stimulating factors，such as CSF (colony stimulating factor), EPO (erythropoietin), within past 2 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;

Sponsors & Collaborators

• Peking University: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (1)

• Lu M, Zhang P, Zhang Y, Li Z, Gong J, Li J, Li J, Li Y, Zhang X, Lu Z, Wang X, Zhou J, Peng Z, Wang W, Feng H, Wu H, Yao S, Shen L. Efficacy, Safety, and Biomarkers of Toripalimab in Patients with Recurrent or Metastatic Neuroendocrine Neoplasms: A Multiple-Center Phase Ib Trial. Clin Cancer Res. 2020 May 15;26(10):2337-2345. doi: 10.1158/1078-0432.CCR-19-4000. Epub 2020 Feb 21.

  PMID: 32086343 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Lin Shen, MD, PhD

  Peking University

  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: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor, Chief of Department of GI Oncology, Peking University Cancer Hospital

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 30, 2017
• Study Start: April 6, 2017
• Primary Completion: December 11, 2018
• Study Completion: May 11, 2019
• Last Updated: June 21, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)