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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03744468
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : May 15, 2020
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
BGB-A425 is a humanized, immunoglobulin gamma-1 (IgG1)-variant monoclonal antibody against TIM-3. Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD-1. This study tests the safety and anti-tumor effect of BGB-A425 in combination with tislelizumab in participants with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Solid Tumors Drug: BGB-A425 Drug: tislelizumab Phase 1 Phase 2

Detailed Description:

Blocking antibodies targeting PD-1 have achieved remarkable results in the treatment of many types of tumors. However, it is also worth noting that this therapeutic strategy typically achieves a < 30% objective response rate (ORR) as a monotherapy in participants whose tumors exhibit low positive PD-L1 expression and/or are microsatellite stable. TIM-3 and PD-1 function as immune checkpoint receptors in the overlapping regulation of immune tolerance and have been shown to be overexpressed on the tumor infiltrating lymphocytes (TILs) from participant samples of various solid tumors including, but not limited to non-small cell lung cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, and gastric carcinoma. Subsequently, the activation of TIM-3 and PD-1 represent TILs from both participants or animals across solid tumor types with the most exhausted immunophenotype (ie, cytokine expression, proliferation etc.), which can be reversed with combined blockade of TIM-3 and PD 1. The overlap in expression and function indicates that TIM-3 and PD-1 cooperate to promote effector cell exhaustion which may impede an effective antitumor immune response. Based upon the overlapping expression profiles and immuno-regulatory functions, the improved in vivo antitumor effects, as well as the potential for TIM-3 mediated adaptive resistance, there is strong scientific rationale to evaluate the antitumor effects derived from the combined blockade of TIM-3 and PD-1 in advanced solid tumors. Accordingly, this study will evaluate the safety and preliminary efficacy of BGB-A425 (anti TIM-3) in combination with tislelizumab (anti PD-1) in participants 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 will continue to evaluate the safety but also focus on the efficacy of the combination in select tumor types.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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 will continue to evaluate the safety but also focus on the efficacy of the combination in select tumor types.
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-TIM-3 Monoclonal Antibody BGB-A425 in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors
Actual Study Start Date : November 13, 2018
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : December 1, 2021

Arm Intervention/treatment
Experimental: Phase 1 Dose Escalation
Dose escalation of BGB-A425 in combination with tislelizumab in participants with advanced solid tumors
Drug: BGB-A425
Humanized IgG1-variant monoclonal antibody against TIM-3

Drug: tislelizumab
Humanized, IgG4-variant monoclonal antibody against PD-1
Other Name: BGB-A317

Experimental: Phase 2 Dose Expansion
Further explore the safety and clinical activity of BGB-A425 in combination with tislelizumab in participants with select advanced solid tumors
Drug: BGB-A425
Humanized IgG1-variant monoclonal antibody against TIM-3

Drug: tislelizumab
Humanized, IgG4-variant monoclonal antibody against PD-1
Other Name: BGB-A317




Primary Outcome Measures :
  1. Phase 1 Dose Escalation [ Time Frame: Approximately 2 years ]
    Safety and tolerability of BGB-A425 in combination with tislelizumab using Common Terminology Criteria for Adverse Events (CTCAE v.5.0) in participants with advanced solid tumors.

  2. Phase 2 Dose Expansion [ Time Frame: Approximately 2 years ]
    Recommended Phase 2 dose (RP2D) of BGB-A425 in combination with tislelizumab [ Phase 1 Dose Escalation - Approximately 1.5 years ]; 3. Anti-tumor activity of BGB-A425 in combination with tislelizumab in participants with select advanced solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1.

  3. Anti-tumor activity of BGB-A425 in combination with tislelizumab in participants with select advanced solid tumors, in terms of objective response rate (ORR) [ Time Frame: Approximately 2 years ]
    Assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1.


Secondary Outcome Measures :
  1. Duration of response (DOR) [ Time Frame: Phase 1 or 2 Expansion - Approximately 2-3 years each ]
    Duration of response (DOR) will be determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1.

  2. Disease control rate (DCR) [ Time Frame: Phase 1 or 2 Expansion - Approximately 2-3 years each ]
    Disease control rate (DCR) will be determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1.

  3. Progression free survival [ Time Frame: Phase 2 Expansion - Approximately 3 years ]
    Progression free survival will be determined from investigator derived tumor assessments per RECIST 1.1.

  4. PK Parameter: Area Under the Curve (AUC), 0 to 21 days [ Time Frame: Phase 1 and Phase 2- Approximately 2-3 years each ]
  5. Pharmacokinetic (PK) Parameter: Minimum Concentration (Cmin) [ Time Frame: Phase 1 and Phase 2- Approximately 2-3 years each ]
  6. PK Parameter: Maximum Concentration (Cmax) [ Time Frame: Phase 1 and Phase 2- Approximately 2-3 years each ]
  7. PK Parameter: Clearance (CL) [ Time Frame: Phase 1 and Phase 2- Approximately 2-3 years each ]
  8. PK Parameter: Volume of Distribution (Vz) [ Time Frame: Phase 1 and Phase 2- Approximately 2-3 years each ]
  9. PK Parameter: terminal half-life (t1/2) [ Time Frame: Phase 1 and Phase 2- Approximately 2-3 years each ]
  10. Immunogenicity as assessed by the presence of anti-drug antibodies [ Time Frame: Phase 1 and Phase 2- Approximately 2-3 years each ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Phase 1: Patients 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.
  2. Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
  3. Has adequate organ function.

Key Exclusion Criteria:

  1. Active, untreated, or uncontrolled brain metastasis or leptomeningeal disease.
  2. Active autoimmune diseases or history of autoimmune diseases that may relapse.
  3. 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.

5. Concurrent participation in another therapeutic clinical trial. 6. Received prior therapies targeting TIM-3.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03744468


Contacts
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Contact: BeiGene 1 (877) 828-5568 clinicaltrials@beigene.com

Locations
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United States, Colorado
University of Colorado Cancer Centre Recruiting
Aurora, Colorado, United States, 80045
United States, Pennsylvania
Fox Chase Cancer Centre Recruiting
Philadelphia, Pennsylvania, United States, 19111
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia
Australia, Western Australia
Linear Clinical Research Recruiting
Perth, Western Australia, Australia
Sponsors and Collaborators
BeiGene
Investigators
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Principal Investigator: Jayesh Desai, MD Peter MacCallum Cancer Centre, Australia
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03744468    
Other Study ID Numbers: BGB-900-102
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms