To Explore the Efficacy and Safety of SHR-1701 Combined With Temozolomide in the Treatment of Advanced Melanoma

A Prospective, Single-center Clinical Study to Explore the Efficacy and Safety of SHR-1701 Combined With Temozolomide in the Treatment of Advanced Melanoma

This study is being conducted to explore the efficacy and safety of SHR-1701 combined with temozolomide in the treatment of advanced melanoma.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Drug: SHR-1701; Drug: Temozolomide

Detailed Description

This trial is a prospective, single-center, single-arm clinical research. Based on current experience, single agent immunotherapy has limited efficacy in advanced melanoma. SHR-1701 is a novel immunotherapy drug . Preclinical data suggest that temozolomide selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with SHR-1701. This study is aiming to evaluate the efficacy and safety of SHR-1701 combined with temozolomide in patients with advanced melanoma. The safety and efficacy of this study will be assessed through ORR, DCR,PFS, OS , and adverse effects as graded by CTCAE 5.0.

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: yong chen, MD; Phone Number: 13917530417; Email: chenyong@fudan.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: yong chen, MD; Phone Number: 13917530417; Email: chenyong@fudan.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Has unresectable Stage III or Stage IV or melanoma per American Joint Committee on Cancer (AJCC) staging system version 8. At least one measurable lesion conforming to RECIST 1.1 criteria.
• No previously received systematic therapy.
• The toxicity of prior treatment has recovered to ≤1 grade according to CTCAE 5.0.
• ECOG score 0-1.
• The expected survival time is ≥ 12 weeks.
• Adequate organ and bone marrow function.
• Female subjects of childbearing age must undergo a serum pregnancy test within 7 days before the commencement of the study and the results are negative, and are willing to use a medically approved high potency contraceptive method during the study period and within 3 months after the last administration of the study drug; For male subjects whose partner is a female of childbearing age, they should be surgically sterilized or agree to use an effective method of contraception during the study period and for 3 months after administration of the last study.
• Willing to consent and signed the informed consent, and able comply with the planned visit, research treatment, laboratory examination and other test procedures.

Exclusion Criteria:

• History of other malignant tumors, except for cured skin basal cell carcinoma, squamous cell carcinoma of skin, superficial bladder carcinoma, papillary thyroid carcinoma, intraductal carcinoma and cervical carcinoma in situ.
• Has ocular melanoma.
• The first study drug treatment was less than 4 weeks from the last systematic antitumor therapy or 5 half-lives from the last targeted therapy; less than 4 weeks from major surgery; less than7 days from immunosuppressive drug; less than 3 weeks from immunomodulatory; less than 4 weeks from live attenuated vaccine.
• Systemic antibiotic use for 7 days within 4 weeks prior to initial administration, or unexplained fever during screening/prior to initial administration.
• With active autoimmune disease or a history of autoimmune disease.
• With history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• With immunodeficiency, eg HIV, HBV, HCV.
• Have a clear history of serious and uncontrolled other disease or mental disorders.
• Has a bleeding tendency or abnormal clotting function.
• Subjects with central nervous system disease or brain metastases.
• Known to be allergic to the active ingredients or excipients in this study.
• Other situations that the researcher considers inappropriate to participate in the research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-1701 combined with temozolomide	Drug: SHR-1701; SHR-1701 combined with temozolomide; Other Names: SHR1701; Drug: Temozolomide; SHR-1701 combined with temozolomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR (Objective Response Rate)	Containing the incidence of complete response (CR) and partial response (PR). Evaluated according to RECIST 1.1 criteria, subjects received their first tumor imaging evaluation at 6 weeks after the treatment start, followed by imaging evaluation every 2 cycles.	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 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS (Progression-Free-Survival)	From date of treatment start until the date of progression or the date of death due to any cause. Evaluated according to RECIST 1.1 criteria, subjects received their first tumor imaging evaluation at 6 weeks after the treatment start, followed by imaging evaluation every 2 cycles.	From date of treatment start until the date of progression or the date of death due to any cause, assessed up to 12 months
DCR (Disease Control Rate)	Containing the incidence of complete response (CR), partial response (PR) and stable disease (SD).Evaluated according to RECIST 1.1 criteria, subjects received their first tumor imaging evaluation at 6 weeks after the treatment start, followed by imaging evaluation every 2 cycles.	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 12 months
OS (overall survival)	From date of treatment start to any cause death or last follow-up.	From date of treatment start until the date of death from any cause or censored at the last day that the subjects are documented to be alive, whichever came first, assessed up to 36 month
6mPFS	6-month- Progression-Free-Survival rate. Evaluated according to RECIST 1.1 criteria, subjects received their first tumor imaging evaluation at 6 weeks after the treatment start, followed by imaging evaluation every 2 cycles.	Up to 6 months
Adverse events (per CTCAE v5.0 criteria)	To evaluate the adverse events of subjects with advanced melanoma after treated with SHR-1701 plus temozolomide	Up to 12months

Collaborators and Investigators

• Sponsor: Yong Chen
• Investigators: Principal Investigator: yong chen, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2022
• Primary Completion (Estimated): September 30, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: November 1, 2021
• First Submitted That Met QC Criteria: November 1, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• 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: MM-1st-IIT-SHR1701-TMZ

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