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

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ClinicalTrials.gov Identifier: NCT03744468
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
BGB-A425 is a humanized, IgG1-variant monoclonal antibody against TIM-3. Tislelizumab is a humanized, IgG4-variant monoclonal antibody against PD-1. This study tests the safety and anti-tumor effect of BGB-A425 in combination with tislelizumab in patients 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 patients 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 patient 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 patients 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 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 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 : August 27, 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 patients 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 patients 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

Experimental: China Sub-Study
Evaluate the safety and PK of BGB-A425 in combination with tislelizumab in Chinese patients 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




Primary Outcome Measures :
  1. Phase 1 Dose Escalation [ Time Frame: Approximately 1.5 years ]
    Safety and tolerability of BGB-A425 in combination with tislelizumab using Common Terminology Criteria for Adverse Events (CTCAE v.5.0) in patients with advanced solid tumors.

  2. Phase 2 Dose Expansion [ Time Frame: Approximately 1.5 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 patients 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.


Secondary Outcome Measures :
  1. Duration of response (DOR) [ Time Frame: Phase 1 or 2 Expansion - Approximately 1.5 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 1.5 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 [ Time Frame: Phase 1 and Phase 2- Approximately 1.5 year each ]
    PK Parameter: AUC, 0 to 21 days

  5. PK Parameter [ Time Frame: Phase 1 and Phase 2- Approximately 1.5 year each ]
    PK Parameter: Minimum Concentration (Cmin)

  6. PK Parameter [ Time Frame: Phase 1 and Phase 2- Approximately 1.5 year each ]
    PK Parameter: Maximum Concentration (Cmax)

  7. PK Parameter [ Time Frame: Phase 1 and Phase 2- Approximately 1.5 year each ]
    PK Parameter: Clearance (CL)

  8. PK Parameter [ Time Frame: Phase 1 and Phase 2-Approximately 1.5 year each ]
    PK Parameter: Volume of Distribution (Vz)

  9. PK Parameter [ Time Frame: Phase 1 and Phase 2- Approximately 1.5 year each ]
    PK Parameter: terminal half-life (t1/2)

  10. Immunogenicity [ Time Frame: Phase 1 and Phase 2- Approximately 1.5 year each ]
    Immunogenicity as assessed by the presence of anti-drug antibodies



Information from the National Library of Medicine

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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

Inclusion Criteria:

  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.

Exclusion Criteria:

  1. Active brain or leptomeningeal metastasis.
  2. Active autoimmune diseases or history of autoimmune diseases that may relapse.
  3. With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
  4. Concurrent participation in another therapeutic clinical trial.
  5. Received prior therapies targeting TIM-3.

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: Brandon Beagle, PhD 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
Principal Investigator: Wells Messersmith         
United States, Pennsylvania
Fox Chase Cancer Centre Recruiting
Philadelphia, Pennsylvania, United States, 19111
Principal Investigator: Crystal Denlinger         
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia
Principal Investigator: Jayesh Desai         
Australia, Western Australia
Linear Clinical Research Recruiting
Perth, Western Australia, Australia
Principal Investigator: Tarek Meniawy         
Sponsors and Collaborators
BeiGene

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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03744468     History of Changes
Other Study ID Numbers: BGB-900-102
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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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Antibodies
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents