Safety and Efficacy Study of QLF31907 in Advanced Melanoma and Urothelial Carcinoma

Study Overview
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Brief Summary
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This study will assess the safety, tolerability and efficacy of every-2-week dosing of QLF31907 injection in patients with advanced melanoma and urothelial carcinoma.

Detailed Description
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This study is divided into two parts. The first part is the safety and tolerability observation period, mainly observing the safety and tolerability of QLF31907. The second part is mainly the efficacy observation period, further evaluating the efficacy and safety of QLF31907 in patients with advanced melanoma and urothelial carcinoma.

Official Title
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A Phase II Study to Evaluate the Efficacy and Safety of QLF31907 Injection in Patients With Advanced Melanoma and Urothelial Carcinoma

Conditions
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Melanoma, Urothelial Carcinoma

Intervention / Treatment
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* Drug: QLF31907


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects voluntarily participated and signed a written informed consent form Age ≥ 18 years, male or female ECOG performance status of 0 or 1 Expected life-expectancy ≥ 3 months Histologically confirmed diagnosis of locally advanced or metastatic unresectable melanoma or urothelial carcinoma, failed or intolerant or rejected to standard therapy Patients must have at least one measurable lesion according to RECIST v1.1 Adequate organ function prior to QLF31907 administration All subjects of reproductive potential must agree to use an effective method of contraception during the study and for 180 days after the last dose, and women of reproductive age must have a negative blood pregnancy result within 7 days prior to the first dose. Exclusion Criteria: Prior treatment with 4-1BB agonist or 4-1BB recombinant fusion protein Known to be allergic to any excipients of QLF31907 or a history of severe allergic reactions to other monoclonal antibodies Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or autologous stem cell transplantation within 180 days Known history of cytotherapy or antitumor vaccine or other antitumor therapy or surgical treatment of main organs within 4 weeks Known history of systemic glucocorticoid therapy or other immunosuppressants within 14 days Active central nervous system (CNS) metastases Known history of other active malignant tumor within 3 years, unless completely cured With uncontrolled or clinically symptomatic pleural, pericardial or abdominal effusions An active infectious disease requiring intravenous antibiotic therapy Failure to recover to grade 1 from adverse reactions due to prior treatment according to CTCAE v5.0 An active autoimmune diseases or known history of ≥ grade 3 irAE due to prior immunotherapy Known history of active hepatitis B/C infection, severe cardiovascular and cerebrovascular disease, idiopathic pulmonary fibrosis, pneumoconiosis, asbestosis, hepatitis (nonalcoholic steatohepatitis, alcoholic or autoimmune hepatitis), cirrhosis, active tuberculosis, active syphilis, HIV infection Poorly controlled respiratory, circulatory or endocrine diseases Known history of drugs abuse, alcoholism, neurologic or psychiatric disorders Patients who are breastfeeding Other serious physical or psychiatric illnesses or laboratory abnormalities that may increase the risk of participating in the study, or interfere with the results of the study, and patients who are not suitable for participation in this study in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QLF31907<br>single arm with QLF31907 | Drug: QLF31907<br>* Intravenous infusion once every two weeks. The dose administered in part 2 will depend on the outcome of part 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (part 1)Dose-limiting toxicity(DLT) |  | 28days | 
| (part 2) Objective response rate(ORR) |  | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (part 2) Safety index: adverse event(AE), serious adverse event (SAE), treatment-related adverse event(TRAE) |  | up to 2 years | 
| (part 2) Progression-free survival(PFS) |  | up to 2 years | 
| (part 2) Overall survival(OS) |  | up to 2 years | 
| (part 2) Maximum observed plasma concentration (Cmax) |  | up to 2 years | 
| (part 2) Positive rate of anti-drug antibody(ADA) |  | up to 2 years |