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

Advanced Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04640545
• Other study ID #: LBL-007-CN-002
• Status: Recruiting
• Phase: Phase 1
• Start date: May 12, 2020
• Est. completion date: December 20, 2024

Study information

• Verified date: December 2023
• Source: Nanjing Leads Biolabs Co.,Ltd
• Contact: Xiangyu Ma
• Phone: 025-83378099-828
• Email: maxy[@]leadsbiolabs.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: December 20, 2024
• Est. primary completion date: August 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Willingness to provide written informed consent and follow the study treatment plan and visit plan;

2. Aged = 18 years at time of signing informed consent, male or female;

3. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1;

4. Have life expectancy of at least 12 weeks ;

5. Subject with at least one measurable tumor lesion,according to the evaluation standard of solid tumor efficacy (RECIST 1.1).

Exclusion criteria:

1. Subjects are allergic to LBL-007, PD-1 and similar compounds or any component in the prescription;

2. 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);

3. Have received major surgery within 4 weeks before the first administration;

4. Subjects can not tolerate intravenous administration and have difficulty in venous blood collection (if there is a history of fainting needles and bleeding);

5. Women during pregnancy or lactation;

Related Conditions & MeSH terms

• Advanced Melanoma
• Melanoma

Intervention

Drug:
• LBL-007
LBL-007 will be administered intravenously every two weeks (Q2W) at doses of Dose A, Dose B, Dose C,Dose D .
• Toripalimab
Toripalimab Injection will be administered by intravenously (Q2W) by the fixed dose of 3 mg/kg .
• Axitinib Tablets
Axitinib Tablets 5mg and Axitinib Tablets 1mg(On-demand administration)

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	the First Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Nanjing Leads Biolabs Co.,Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)