Phase Ib/II Clinical Study of LBL-007 in Treatment of Advanced Malignant Tumors

Study Overview
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Brief Summary
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This trial is a single-arm, open, multi-center phase Ib/II clinical study, which aims to evaluate the safety, tolerability, PK characteristics, immunogenicity, and Effectiveness.

Detailed Description
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This trial is divided into the combined dose escalation (Phase Ib) and the expansion phase (Phase II), as follows: In the phase Ib study, it is planned to include patients with advanced malignant tumors who have no standard treatment or who have failed the previous standard treatment or who do not apply standard treatment at this stage. According to the rolling six design dose escalation method, the tolerability of LBL-007 200 and 400 mg dose levels was evaluated. Each dose group included 3 to 6 subjects, and the total sample size for stage Ib was about 9-12 (specifically The sample size is subject to actual occurrence). The dosage regimen of LBL-007 is once every 3 weeks (Q3W), intravenous infusion; the dosage regimen of combination drug teriprizumab is 240 mg, once every 3 weeks (Q3W), intravenous Infusion. During the experiment, necessary adjustments can be made to the dosing frequency or incremental group settings based on the PK data and safety data obtained. In this study, every 3 weeks is a dosing cycle, and the DLT observation period is 3 weeks after the first dosing. According to the LBL-007 global research and development data and the safety, tolerability and PK data of the phase Ib clinical study, the recommended dose of phase II clinical study (RP2D) was obtained for the expansion of target indications, including advanced esophageal squamous cell carcinoma, head Patients with malignant tumors such as cervical squamous cell carcinoma, cervical cancer, and nasopharyngeal carcinoma. During the screening period of this study, subjects need to undergo relevant inspections or observations, and those who meet the screening requirements will enter the treatment period. During the treatment period, all subjects will receive a certain dose of the test drug combined with teriprizumab until intolerable toxicity, disease progression, death, voluntary withdrawal, loss to follow-up, or continuous administration for 2 years ( Whichever occurs first). Subjects will be evaluated for anti-tumor efficacy according to the efficacy evaluation criteria for solid tumors (RECIST V1.1) and immunotherapy solid tumor efficacy evaluation criteria (iRECIST), once every 6 weeks after the first administration, and the frequency will be adjusted after 24 weeks It is once every 9 weeks. All subjects in this study will have a safety follow-up 30 days (+7 days) after the last administration or before starting a new anti-tumor therapy, and then enter the survival follow-up, and will collect whether to accept new anti-tumor therapy and survival information, etc. , Until the subject's death or loss to follow-up or withdrawal of informed consent. In this trial, all subjects in phase Ib/II underwent a sparse blood sampling population PK study; all subjects collected blood samples for the evaluation of LBL-007 immunogenicity; all subjects collected tumor tissue samples for biomarkers For related explorations, some subjects will collect blood samples for explorations related to receptor occupancy.

Official Title
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A Multicenter Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LBL-007 in Combination With Toripalimab in the Treatment of Advanced Malignancies

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: LBL-007 Injection
* Drug: Toripalimab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Agree to follow the experimental treatment plan and visit plan, join the group voluntarily, and sign a written informed consent form; Age ≥ 18 and ≤ 75 years old when signing the informed consent form, regardless of gender; The Eastern Cooperative Oncology Group's physical status scoring standard (ECOG) PS is 0 1; The expected survival time is at least 12 weeks; Males with fertility and females of childbearing age are willing to take effective contraceptive measures From the signing of the informed consent form to within 6 months after the last administration of the trial drug (including abstinence, intrauterine device, various hormonal contraception, correct use of contraception Sets，etc）; Women of childbearing age include pre-menopausal women and women within 2 years after menopause. Women of childbearing age must have a negative pregnancy test within 7 days before the first trial drug is administered. Exclusion Criteria: Have received other unmarketed clinical research drugs or treatments within 4 weeks before using the research drug for the first time; Those who have used anti-LAG-3 antibody immunotherapy in the past; Those who have clinically uncontrollable pleural effusion, pericardial effusion or ascites, requiring repeated drainage or medical intervention; History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation, except for those who do not need to use immunosuppressive agents (such as corneal transplantation); Women during pregnancy or lactation; The investigator believes that the subject has other conditions that may affect compliance or are not suitable for participating in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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<br>LBL-007 Injection; dose A or dose B; Q3W | Drug: LBL-007 Injection<br>* LBL-007 Injection; dose A or dose B; Q3W<br>* Other names: LBL-007;Drug: Toripalimab Injection<br>* Toripalimab is infused with a fixed dose of 3 mg/kg intravenously every three weeks<br>|

What is the study measuring?
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Primary 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 (30+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Dose-limiting toxicities（DLT） | DLT is defined as toxicity (at least possible adverse events related to LBL-007) during the DLT observation period (3 weeks after the first dose). | During the first Cycles(each cycle is 21 days) | 
| 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 cycles. | During the first Cycles(each cycle is 21 days) | 

Secondary 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 enent(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 (30+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 (30+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 (30+7 days after drug withdrawal or before the start of new anti-tumor therapy) |