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

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

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

Study Overview

• Status: Recruiting
• Conditions: Advanced Melanoma
• Intervention / Treatment: Drug: LBL-007; Drug: Toripalimab; Drug: Axitinib Tablets

Detailed 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

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ting Lv; Phone Number: 025-83378099-829; Email: lvting@leadsbiolabs.com
• Study Contact Backup: Name: Xiangyu Ma; Phone Number: 025-83378099-828; Email: maxy@leadsbiolabs.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Xiangyu Ma; Phone Number: 025-83378099-828; Email: maxy@leadsbiolabs.com
      • Contact: Ting Lv; Phone Number: 025-83378099-829
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: ting lv; Phone Number: 025-83378099; Email: lvting@leadsbiolabs.com
      • Contact: xiangyu ma; Phone Number: 025-83378099; Email: maxy@leadsbiolabs.com
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
      • Contact: xiangyu ma; Phone Number: 02583378099; Email: maxy@leadsbiolabs.com
      • Contact: ting lv; Phone Number: 02583378099; Email: lvting@leadsbiolabs.com
  • Hunan
    • Changsha, Hunan, China, 410006
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Xiangyu Ma; Phone Number: 025-83378099-828; Email: maxy@leadsbiolabs.com
      • Contact: Ting Lv; Phone Number: 025-83378099-829
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Nanjing Drum Tower Hospital
      • Contact: ting lv; Phone Number: 025-83378099; Email: lvting@leadsbiolabs.com
      • Contact: xiangyu ma; Phone Number: 025-83378099; Email: maxy@leadsbiolabs.com
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: xiangyu ma; Phone Number: 02583378099; Email: maxy@leadsbiolabs.com
      • Contact: ting lv; Phone Number: 02583378099; Email: lvting@leadsbiolabs.com
    • Changchun, Jilin, China, 130021
      • Recruiting
      • Jilin Cancer Hospital
      • Contact: ting lv; Phone Number: +862583378099; Email: lvting@leadsbiolabs.com
      • Contact: xiangyu ma; Phone Number: 02583378099; Email: maxy@leadsbiolabs.com
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Xiangyu Ma; Phone Number: 025-83378099-828; Email: maxy@leadsbiolabs.com
      • Contact: Ting Lv; Phone Number: 025-83378099-829

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)

Collaborators and Investigators

• Sponsor: Nanjing Leads Biolabs Co.,Ltd
• Investigators: Principal Investigator: Jun Guo, Prof, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2020
• Primary Completion (Estimated): August 10, 2024
• Study Completion (Estimated): December 20, 2024

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: LBL-007-CN-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No