Description:
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.
Title
- Brief Title: Study of BGB-A425 in Combination With Tislelizumab in Advanced Solid Tumors
- 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
Clinical Trial IDs
- ORG STUDY ID:
BGB-900-102
- NCT ID:
NCT03744468
Conditions
- Locally Advanced or Metastatic Solid Tumors
Interventions
| Drug | Synonyms | Arms |
|---|
| BGB-A425 | | Phase 1 Dose Escalation |
| tislelizumab | BGB-A317 | Phase 1 Dose Escalation |
Purpose
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.
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Phase 1 Dose Escalation | Experimental | Dose escalation of BGB-A425 in combination with tislelizumab in patients with advanced solid tumors | |
| Phase 2 Dose Expansion | Experimental | Further explore the safety and clinical activity of BGB-A425 in combination with tislelizumab in patients with select advanced solid tumors | |
Eligibility 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase 1 Dose Escalation |
| Time Frame: | Approximately 1.5 years |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Duration of response (DOR) |
| Time Frame: | Phase 1 or 2 Expansion - Approximately 1.5 years each |
| Safety Issue: | |
| Description: | Duration of response (DOR) will be determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. |
| Measure: | Disease control rate (DCR) |
| Time Frame: | Phase 1 or 2 Expansion - Approximately 1.5 years each |
| Safety Issue: | |
| Description: | Disease control rate (DCR) will be determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. |
| Measure: | Progression free survival |
| Time Frame: | Phase 2 Expansion - Approximately 3 years |
| Safety Issue: | |
| Description: | Progression free survival will be determined from investigator derived tumor assessments per RECIST 1.1. |
| Measure: | PK Parameter |
| Time Frame: | Phase 1 and Phase 2- Approximately 1.5 year each |
| Safety Issue: | |
| Description: | PK Parameter: AUC, 0 to 21 days |
| Measure: | PK Parameter |
| Time Frame: | Phase 1 and Phase 2- Approximately 1.5 year each |
| Safety Issue: | |
| Description: | PK Parameter: Minimum Concentration (Cmin) |
| Measure: | PK Parameter |
| Time Frame: | Phase 1 and Phase 2- Approximately 1.5 year each |
| Safety Issue: | |
| Description: | PK Parameter: Maximum Concentration (Cmax) |
| Measure: | PK Parameter |
| Time Frame: | Phase 1 and Phase 2- Approximately 1.5 year each |
| Safety Issue: | |
| Description: | PK Parameter: Clearance (CL) |
| Measure: | PK Parameter |
| Time Frame: | Phase 1 and Phase 2-Approximately 1.5 year each |
| Safety Issue: | |
| Description: | PK Parameter: Volume of Distribution (Vz) |
| Measure: | PK Parameter |
| Time Frame: | Phase 1 and Phase 2- Approximately 1.5 year each |
| Safety Issue: | |
| Description: | PK Parameter: terminal half-life (t1/2) |
| Measure: | Immunogenicity |
| Time Frame: | Phase 1 and Phase 2- Approximately 1.5 year each |
| Safety Issue: | |
| Description: | Immunogenicity as assessed by the presence of anti-drug antibodies |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | BeiGene |
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