A Study to Assess LBL-007 in Combination With Toripalimab and Axitinib Tablets Subjects With Advanced Melanoma

Study Overview
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Brief Summary
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A phase I clinical study evaluating LBL-007 in the treatment of subjects with advanced solid tumors

Detailed Description
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This trial is a multi-center, single-arm, open-label, dose-escalation and expansion phase I study of LBL-007 combined with Toripalimab and Axitinib in the treatment of unresectable or metastatic melanoma. It is divided into Study Part A and Study Part B. The safety, tolerability, kinetic characteristics, immunogenicity and preliminary efficacy of the subjects were evaluated. Both study part A and study part B are studied in two phases: dose escalation and dose expansion

Official Title
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A Phase I Multi-center Study to Evaluate the Safety ,Tolerability and Efficacy of LBL-007 Combined With Toripalimab or LBL-007 Combined With Toripalimab and Axitinib Tablets in the Treatment of Unresectable or Metastatic Melanoma

Conditions
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Advanced Melanoma

Intervention / Treatment
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* Drug: LBL-007
* Drug: Toripalimab
* Drug: Axitinib Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness to provide written informed consent and follow the study treatment plan and visit plan; Aged ≥ 18 years at time of signing informed consent, male or female; Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1; Have life expectancy of at least 12 weeks ; Subject with at least one measurable tumor lesion,according to the evaluation standard of solid tumor efficacy (RECIST 1.1). Exclusion criteria: Subjects are allergic to LBL-007, PD-1 and similar compounds or any component in the prescription; Subjects with active central nervous system metastases (regardless of whether they have received treatment), including symptomatic brain metastases, meningeal metastases, or spinal cord compression, but asymptomatic brain metastases (no progression and/or at least 4 weeks after radiotherapy) No neurological symptoms or signs after surgical resection, and dexamethasone or mannitol treatment is not required); Have received major surgery within 4 weeks before the first administration; Subjects can not tolerate intravenous administration and have difficulty in venous blood collection (if there is a history of fainting needles and bleeding); Women during pregnancy or lactation;

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LBL-007+Toripalimab+Axitinib Tablets<br>Study Part A： LBL-007 Dose A/Dose B/Dose C/Dose D Q2W iv+Toripalimab 3mg/kg Q2W iv； Study Part B： LBL-007 Dose A/Dose B/Dose C/Dose D Q2W iv+Toripalimab 3mg/kg Q2W iv+Axitinib Tablets 5mg + Axitinib Tablets 1mg | Drug: LBL-007<br>* LBL-007 will be administered intravenously every two weeks (Q2W) at doses of Dose A, Dose B, Dose C,Dose D .<br>Drug: Toripalimab<br>* Toripalimab Injection will be administered by intravenously (Q2W) by the fixed dose of 3 mg/kg .<br>Drug: Axitinib Tablets<br>* Axitinib Tablets 5mg and Axitinib Tablets 1mg(On-demand administration)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjcects with adverse events and serious adverse events | The safety profile of LBL-007 and Toripalimab will be assessed by monitoring the adverse event(AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE)v5.0 | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Maximum tolerated dose (MTD) | MTD is defined as the hightest dose level at which no more than 1 out of 6 subjects experiences a DLT during the first two cycles. | During the first two Cycles(each cycle is 14 days) | 
| Dose-limiting toxicities (DLT) | DLT is defined as a toxicities(adverse event at least possibly related to LBL-007 and Toripalimab )occurring during the DLT observation period(the initial 28 days). | During the first two Cycles(each cycle is 14 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Defined as the percentage of subjects having a Complete Response or Partial Response(ORR, including after immunotherapy complete response (iCR) and partial response (iPR)),will be determined by investigator assessment of radiographic disease assessments per RECIST v1.1. and iRECIST. | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Duration of Response(DOR) | Defined as the time from earliest date of disease response (CR 、PR、iCR、iPR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease per RECIST v1.1 and iRECIST, or death from any cause, if occurring sooner than progression. | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Disease Control Rate(DCR) | Defined as percentage of participants having CR, PR, iCR，iPR or SD as best on-study response | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Steady state Area under the serum concentration versus time curve（AUCss） | To determine the PK profile of LBL-007 in combination with Toripalimab | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Steady state Maximum serum concentration (Cmax,ss) | To determine the PK profile of LBL-007 in combination with Toripalimab | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Steady state Time to reach maximum serum concentration (Tmax,ss) | To determine the PK profile of LBL-007 in combination with Toripalimab | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Pharmacodynamic (PD) index | The PD evaluation index is the LAG-3 receptor occupancy rate in peripheral blood | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Immunogenicity index | The immunogenicity evaluation indicators are the incidence of anti-drug antibodies (ADA) and the incidence of neutralizing antibodies (if applicable) in the subject. | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (28+7 days after drug withdrawal or before the start of new anti-tumor therapy) |