Study of BGB-A425 and LBL-007 in Combination With Tislelizumab in Advanced Solid Tumors

NCT ID: NCT03744468

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-13
• Study Completion Date: 2025-02-06

Brief Summary

This is an open-label, multicenter, nonrandomized Phase 1 and 2 clinical trial evaluating various combinations of BGB-A425 and/or LBL-007 with tislelizumab.

Detailed Description

Blocking antibodies targeting PD-1 have achieved remarkable results in the treatment of many types of tumors. However, based upon the rate of primary and secondary resistance to PD-1 blockade, it is apparent that additional immuno-regulatory mechanism(s) underlie tumor immune escape. Indeed, research shows that the TIM-3 pathway cooperates with PD-1 to maximize the suppression of effector TILs as well as promote resistance to anti-PD-1 therapy. Therefore, TIM-3 represents an ideal target with the potential to significantly improve and/or extend the therapeutic benefit of anti-PD-1 therapy to a greater number of patients.

TIM3, LAG3, and PD-1 function as immune checkpoint receptors in the overlapping regulation of immune tolerance and have been shown to be co-overexpressed on the tumor infiltrating lymphocytes (TILs) from the participant samples of various solid tumors. Furthermore, emerging clinical data and preclinical data demonstrate co-expression of Tim-3, LAG-3, PD-1 often yield T cells' exhausted immunophenotype (ie, cytokine expression, proliferation etc.). Cancer cells take advantage of PD-1, TIM-3, and LAG-3 in inhibiting immune cells' function, and escape the immune surveillance. Based upon the overlapping expression profiles and immuno-regulatory functions, TIM-3 and LAG-3 mediated adaptive resistance, there is strong scientific rationale that simultaneous targeting of these checkpoint blockers, could potentially increase therapeutic benefit and may help to overcome the resistance arising due to anti-PD-(L)-1 therapy. Hence, this study will evaluate the safety and preliminary efficacy of BGB-A425 (anti TIM-3), LBL-007 (Anti-LAG-3) in combination with tislelizumab (anti PD-1) in patients with advanced solid tumors

This is an open-label, multicenter, nonrandomized Phase 1 and Phase 2 clinical trial. Phase 1 will determine the recommended phase 2 dose (RP2D) for the combination of BGB-A425 and Tislelizumab. Phase 2 safety lead-in will determine the RP2D for the combination of BGB-A425, Tislelizumab and/or LBL-007. Phase 2 dose expansion will continue to evaluate the safety but also focus on the efficacy of the doublet or triplet treatment combination in select tumor types.

Conditions

Locally Advanced or Metastatic Solid Tumors for Phase 1,Dose Escalation and Phase 2 Safety Lead-in, HNSCC, NSCLC and RCC Participants for Phase 2

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Dose Escalation

Dose escalation of BGB-A425 in combination with Tislelizumab in participants with advanced solid tumors

Group Type: EXPERIMENTAL

BGB-A425

Intervention Type: DRUG

Humanized IgG1-variant monoclonal antibody against TIM-3

Tislelizumab

Intervention Type: DRUG

Humanized, IgG4-variant monoclonal antibody against PD-1

Phase 2 Safety Lead-in

Dose escalation for Cohort A (LBL-007 + Tislelizumab) and Cohort B (BGB-A425 + LBL-007 + Tislelizumab) in participants with advanced solid tumors

Group Type: EXPERIMENTAL

BGB-A425

Intervention Type: DRUG

Humanized IgG1-variant monoclonal antibody against TIM-3

Tislelizumab

Intervention Type: DRUG

Humanized, IgG4-variant monoclonal antibody against PD-1

LBL-007

Intervention Type: DRUG

Human anti LAG-3 IgG4-kappa antibody

Phase 2 Dose Expansion

Further explore the safety and clinical activity of BGB-A425 and LBL-007 in combination with Tislelizumab in participants with NSCLC, HNSCC and RCC

Group Type: EXPERIMENTAL

BGB-A425

Intervention Type: DRUG

Humanized IgG1-variant monoclonal antibody against TIM-3

Tislelizumab

Intervention Type: DRUG

Humanized, IgG4-variant monoclonal antibody against PD-1

LBL-007

Intervention Type: DRUG

Human anti LAG-3 IgG4-kappa antibody

Interventions

BGB-A425

Humanized IgG1-variant monoclonal antibody against TIM-3

Intervention Type: DRUG

Tislelizumab

Humanized, IgG4-variant monoclonal antibody against PD-1

Intervention Type: DRUG

LBL-007

Human anti LAG-3 IgG4-kappa antibody

Intervention Type: DRUG

Other Intervention Names

Surzebiclimab; BGB-A317; Alcestobart

Eligibility Criteria

Inclusion Criteria

Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.

• Adequate organ function
• Phase 1 Dose Escalation + Phase 2 Safety Lead-In: Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for which treatment is not available, not tolerated or refused.
• Phase 2 Dose-Expansion: Participants with one of the following histologically or cytologically confirmed solid tumors:
• For HNSCC participants in cohort 1,4 and 6 (PD-L1 positive):

Recurrent/metastatic head and neck squamous cell cancer of the oral cavity, oropharynx, hypopharynx, and/or larynx whose tumor is not amenable to local therapy with curative intent (ie, surgery or radiation therapy with or without chemotherapy • For NSCLC participants in Cohort 2, 5 and 7 (PD-L1 positive): Locally recurrent Stage IIIB, stage IIIC or Stage IV squamous or non-squamous non-small cell lung cancer

• For RCC participants in Cohort 3: Locally advanced unresectable or metastatic and histologically confirmed renal cell carcinoma with a clear cell histology

Exclusion Criteria

• NSCLC patients with known EGFR mutation, BRAF mutation, ALK fusion, or ROS1 fusion
• Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
• Active autoimmune diseases or history of autoimmune diseases that may relapse.
• Interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases
• Uncontrolled diabetes or significant cardiac issues
• Infections requiring systemic antibacterial, antifungal, or antiviral therapy
• History of severe hypersensitivity reactions to other monoclonal antibodies
• History of HIV infection or untreated chronic hepatitis B or chronic hepatitis B virus carriers
• Major surgical procedure within 28 days before study drug administration
• Chemotherapy, radiotherapy, immunotherapy or any investigational therapies within 28 days (PH 2 Safety Lead-In) or 14 days (PH 2 Dose Expansion) or 5 half-lives of (whichever is shorter) of first administration of study drug(s).
• With infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 14 days prior to the first dose of study drug(s), or a requirement for chronic prophylactic treatment with antibiotics.
• Concurrent participation in another therapeutic clinical trial
• Received prior therapies targeting TIM-3and/or LAG3

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

BeiGene

Locations

Chao Family Comprehensive Cancer Center

Orange, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

University of Chicago Medical Center

Chicago, Illinois, United States

University of Kentucky Markey Cancer Center

Lexington, Kentucky, United States

Weill Cornell Medical College Newyork Presbyterian Hospital

New York, New York, United States

University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

The University of Texas Md Anderson Cancer Center

Houston, Texas, United States

Ut Health San Antonio Mays Cancer Center

San Antonio, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Schar Cancer Institute

Fairfax, Virginia, United States

Sydney Southwest Private Hospital

Liverpool, New South Wales, Australia

Sunshine Coast Hospital and Health Service

Birtinya, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Calvary North Adelaide Hospital

North Adelaide, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Cabrini Research and Education Institute

Malvern, Victoria, Australia

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Western Health Sunshine Hospital

St Albans, Victoria, Australia

Hollywood Private Hospital

Nedlands, Western Australia, Australia

Linear Clinical Research

Nedlands, Western Australia, Australia

Centre de Lutte Contre Le Cancer Institut Bergonie

Bordeaux, , France

Centre de Lutte Contre Le Cancer Francois Baclesse

Caen, , France

Irccs Azienda Ospedaliero Universitaria Bologna

Bologna, , Italy

Fondazione Irccs Istituto Nazionale Dei Tumori

Milan, , Italy

Istituto Di Candiolo Irccs

Torino, , Italy

Centrum Onkologiiim Prof F Lukaszczyka Wbydgoszczy

Bydgoszcz, , Poland

Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy

Warsaw, , Poland

Chungbuk National University Hospital

Cheongju-si, Chungcheongbukdo, South Korea

The Catholic University of Korea, St Vincents Hospital

Suwon, Gyeonggi-do, South Korea

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea

Gachon University Gil Medical Center

Incheon, Incheon Gwang'yeogsi, South Korea

Severance Hospital Yonsei University Health System

Seoul, Seoul Teugbyeolsi, South Korea

Asan Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

The Catholic University of Korea, Seoul St Marys Hospital

Seoul, Seoul Teugbyeolsi, South Korea

Ulsan University Hospital

Donggu, Ulsan Gwang'yeogsi, South Korea

Institut Catala Doncologia

Barcelona, , Spain

Ico Hug Trias I Pujol

Barcelona, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario Hm Madrid Sanchinarro

Madrid, , Spain

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Countries

United States; Australia; France; Italy; Poland; South Korea; Spain

Other Identifiers

U1111-1278-0027

Identifier Type: OTHER

Identifier Source: secondary_id

2022-500694-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BGB-900-102

Identifier Type: -

Identifier Source: org_study_id