Safety and Efficacy of Recombinant Humanized Anti-PD-1 mAb for Patients With Locally Advanced or Metastatic Melanoma

NCT03013101 | Unknown Phase 2 DMC

• 1 other identifier: Junshi-JS001-BJZL-II
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multi-center, open-label, phase 2 study evaluating the humanized anti-PD-1 antibody JS001, as a monotherapy in patients with locally advanced or metastatic melanoma who have failed in routine systemic treatment.

Conditions

Advanced Melanoma; Metastatic Melanoma

Keywords

anti-PD-1 monoclonal antibody; advanced; metastatic; melanoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by RECIST 1.1 and irRECIST Objective response rate (ORR) by RECIST 1.1 and irRECIST

  3 years

Secondary Outcomes (5)

• Duration of response (DOR) by RECIST1.1 and irRECIST

  3 years

• Progression free survival (PFS) by RECIST1.1 and irRECIST

  3 years

• Overall survival (OS)

  3 years

• Immunogenicity of anti-PD-1 monoclonal antibody

  1.5 years

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

  1.5 years

Other Outcomes (1)

• Correlation analysis of PD-L1 expression of tumor by Immunohistochemistry and ORR

  3 years

Study Arms (1)

humanized anti-PD-1monoclonal antibody

EXPERIMENTAL

humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg Q2w 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-1monoclonal antibody

Eligibility Criteria

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

You may qualify if:

• 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 melanoma, while ocular melanoma is excluded, and the overall rate of mucousal melanoma is no more than 25%.
• Have failed at least 1 prior routine regimen for advanced disease.
• Providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes);
• documentary evidence of BRAF mutation status;
• 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 \>=3 months;
• Brain or meningeal metastases must be disposed with surgery or radiation, and be stable clinically for at least 3 months (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) PT/INR, aPTT≤1.5 x ULN;
• 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:

• Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody;
• Hypersensitivity to recombinant humanized anti-PD-1 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

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (6)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Sun Yat-sen University Cancer center

Guangzhou, Guangdong, China

Location

Wuhan Union Hospital

Wuhan, Hubei, China

Location

The 81st Hospital of Chinese People's Liberation Army

Nanjing, Jiangsu, China

Location

The First Hospital of Jilin University

Changchun, Jilin, China

Location

Yunnan Cancer Hospital

Kunming, Yunnan, China

Location

Related Publications (2)

• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

  PMID: 22658127 BACKGROUND

• Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3.

  PMID: 24590637 BACKGROUND

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jun Guo, PhD, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 6, 2017
• Study Start: December 28, 2016
• Primary Completion: September 16, 2018
• Study Completion: December 1, 2021
• Last Updated: September 30, 2020

Record last verified: 2020-09

Locations

CN (6)