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.

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.

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.