A Study of Toripalimab or Combining With Temozolomide（iv） in the Treatment of Advanced/Metastatic Malignant Melanoma

An Exploratory Study of PD-1 Antibody(Toripalimab) or Combining With Temozolomide for Injection in the Treatment of Advanced/Metastatic Malignant Melanoma

This study evaluate toripalimab or combining with temozolomide for injection in the treatment of advanced/metastatic malignant melanoma. Participants in arm A receive toripalimab, in arm B receive toripalimab plus temozolomide

Study Overview

• Status: Recruiting
• Conditions: Malignant Melanoma
• Intervention / Treatment: Drug: toripalimab; Drug: Temozolomide Injection

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yu Zheng, PhD; Phone Number: 13588166206; Email: drzhengyu@126.com
• Study Contact Backup: Name: Cheng Xiao, PhD; Phone Number: 13588166206; Email: drzhengyu@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • Department of Medical Onocology, First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• •Confirmed pathologic or cytologic diagnosis of advanced/metastatic malignant melanomawithout BRAF V600E mutation

  • ECOG PS 0-1;
  • Age :18 ~75 years old;
  • There were measurable lesions according to RECIST 1.1 and the lesions that had been irradiated showed definite progression after radiotherapy and the lesion was considered measurable only if it was not the only lesion
  • Proper function of the cardiovascular system, liver, kidney and bone marrow ;
  • Subject with at most one systemic therapy for advanced/metastatic malignant melanoma
  • Survival is expected to exceed 3 months
  • The subjects showing good compliance voluntarily participated in the study and signed the informed consent

Exclusion Criteria:

• •Previously treated with TMZ, PD-1, or PD-L1;

  • Complicated with other malignant tumors;
  • Subjects with central nervous system metastases and/or cancerous meningitis;(Unless the subjects are asymptomatic or have been treated , no radiographic evidence of new BMs or BMs enlargement is found at least 2 weeks after BMs treatment.If the subjects have active or new untreated asymptomatic central nervous system (CNS) metastases found on imaging during the screening phase,they must receive radiotherapy
  • Uncontrolled pleural effusion ,pericardial effusion or ascites requiring repeated drainage
  • Received major surgical treatment or significant traumatic injury within Random 28 days prior
  • Severe arterial/venous thrombosis events，Such as cerebrovascular accident (including temporary ischemic attack) ,deep vein thrombosis and pulmonary embolismwithin Random 6 months prior
  • Subjects with a history of psychotropic substance abuse and being unable to get rid of it or with mental disorders

  • Subjects with any severe and/or uncontrolled disease,including :

    1. Subjects with poor blood pressure control (systolic≥ 150 mmHg or diastolic ≤100mmHg)
    2. Subjects with myocardial ischemia or myocardial infarction or arrhythmia above grade I (including male QTC ≥450ms(male) and female QTC ≥470ms) And ≥grade 2 congestive heart failure (New York Heart Association (NYHA))
    3. Active or uncontrolled severe infection (≥CTC AE grade 2 infection)
    4. liver cirrhosis,active hepatitis*;*active hepatitis(Hepatitis B reference: HBsAg positive, and HBV DNA test value exceeds the normal valueHepatitis C reference: HCV antibody positive, and HCV virus titer detection value exceeds the upper limit of normal value
    5. HIV infected
    6. Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L)
    7. urine protein≥++,andConfirmated 24-hour urinary protein quantification>1.0 g
    8. Subjects received a preventive vaccineor attenuated vaccine within 4 weeks
    9. prior to first administration
    10. Participated in other clinical trials within 4 weeks
    11. Active autoimmune disease（Such as the following, but not limited to: autoimmune hepatitis interstitial pneumonia enteritis vasculitis, nephritis。Subjects with asthma requiring bronchodilators for medical intervention were not included） requiring systemic treatment（Such as the use of palliative drugs, corticosteroids, or immunosuppressants） occurred within 2 years prior to initial administration.Alternative therapy(Examples include thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy
    12. Other conditions that investigators consider the patients are not suitable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; toripalimab 3mg/kg, Q2w;	Drug: toripalimab; toripalimab 3mg/kg, Q2w; Other Names: triprizumab
Experimental: Arm B; toripalimab 3mg/kg, Q2w; Temozolomide 150mg/m2,d1-5,Q4w	Drug: toripalimab; toripalimab 3mg/kg, Q2w; Other Names: triprizumab; Drug: Temozolomide Injection; Temozolomide 150mg/m2,d1-5,Q4w; Other Names: Temoda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	objective response rate	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	3 years
PFS	Progression free survival	1 years
DCR	Disease contral rate	8 weeks
1-year PFS	progression free survival at 1 year (1year PFS) rate	1 year after treatment initiation
6-month PFS	progression free survival at 6 months (6-month PFS) rate	6 months after treatment initiation
1-year OS	overall survival at 1 year (1 year OS) rate	1 year after treatment initiation
2-year OS	overall survival at 2 years (2 year OS) rate	2 year after treatment initiation

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Principal Investigator: Yulong Zheng, PhD, First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2021
• Primary Completion (Anticipated): March 7, 2024
• Study Completion (Anticipated): September 7, 2024

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: toripalimab; malignant melanoma; PD-1 antibody; temozolomide for injection
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: IIT20210021C-R1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No