Clinical Trials /

BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors

NCT04649385

Description:

The primary objective of this study is to assess the safety and tolerability of BGB-15025 alone and in combination with tislelizumab; and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended Phase 2 doses (RP2D) of BGB-15025 alone and in combination with tislelizumab in participants with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors
  • Official Title: A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of HPK1 Inhibitor BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BGB-A317-15025-101
  • NCT ID: NCT04649385

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
BGB-15025Phase 1a: Dose Escalation
TislelizumabBGB-A317Phase 1a: Dose Escalation

Purpose

The primary objective of this study is to assess the safety and tolerability of BGB-15025 alone and in combination with tislelizumab; and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended Phase 2 doses (RP2D) of BGB-15025 alone and in combination with tislelizumab in participants with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Phase 1a: Dose EscalationExperimentalPart A: Participants will receive once daily of BGB-15025 monotherapy in sequential cohorts of approximately 5 increasing doses for up to 6 months Part B: Participants will receive once daily of BGB-15025 in sequential cohorts plus 200mg tislelizumab on day 1 of each 21-day cycle (combination therapy ) for up to 12 months
  • BGB-15025
  • Tislelizumab
Phase 1b: Dose ExpansionExperimentalPhase 1b dose expansion will begin based upon the recommended Phase 2 dose (RP2D) for BGB-15025 alone or in combination with tislelizumab as determined from Phase 1a
  • BGB-15025
  • Tislelizumab

Eligibility Criteria

        Key Inclusion Criteria:

          1. Phase 1a (dose escalation): Participants with histologically or cytologically
             confirmed advanced, metastatic, and unresectable solid tumors who have previously
             received standard systemic therapy or for whom treatment is not available, not
             tolerated or refused, and who have not received prior therapy targeting HPK1

          2. At least 1 measurable lesion as defined per RECIST 1.1. The target lesion(s) selected
             have not been previously treated with local therapy or the target lesion(s) selected
             that are within the field of prior local therapy have subsequently progressed as
             defined by RECIST 1.1

          3. Participants must be able to provide an archived formalin-fixed paraffin embedded
             (FFPE) tumor tissue sample (block or approximately 15 to 17 freshly unstained FFPE
             slides after the most recent line of therapy. If archival tissue is not available,
             fresh tumor biopsy is mandatory

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

          5. Adequate organ function as indicated by the following laboratory values up to first
             dose of study drug: Hemoglobin≥ 90 g/L, Absolute neutrophil count ≥ 1.5 x 109/L ,
             Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for participants with Gilbert syndrome ),
             AST and ALT≤ 2.5 x ULN (≤5 x ULNs for participants with hepatocellular carcinoma or
             liver metastases )

        Key Exclusion Criteria:

          1. Active leptomeningeal disease or uncontrolled and untreated brain metastasis.
             Participants with equivocal findings or with confirmed brain metastases are eligible
             for enrollment provided that they are asymptomatic and radiologically stable without
             the need for corticosteroid treatment for at least 4 weeks prior to the first dose of
             study drug(s)

          2. Active autoimmune diseases or history of autoimmune diseases that may relapse, with
             the following exceptions:

               1. Controlled Type 1 diabetes

               2. Hypothyroidism (provided that it is managed with hormone-replacement therapy
                  only)

               3. Controlled celiac disease

               4. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or
                  alopecia)

               5. Any other disease that is not expected to recur in the absence of external
                  triggering factors

          3. Any active malignancy ≤ 2 years before the first dose of study drug(s) except for the
             specific cancer under investigation in this study and any locally recurring cancer
             that has been treated with curative intent (eg, resected basal or squamous cell skin
             cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)

          4. Any condition that required systemic treatment with either corticosteroids (> 10 mg
             daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days
             before the first dose of study drug(s), with the following exceptions:

               1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)

               2. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with
                  minimal systemic absorption

               3. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for
                  contrast dye allergy) or for the treatment of a nonautoimmune condition (eg,
                  delayed-type hypersensitivity reaction caused by contact allergen)

          5. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung
             diseases including but not limited to pulmonary fibrosis, acute lung diseases, etc.

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants Experiencing Adverse Events (AEs)
Time Frame:Up to 6 months
Safety Issue:
Description:The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%

Secondary Outcome Measures

Measure:Overall Response Rate (ORR) as assessed by the investigator
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:Duration Of Response (DOR) as assessed by the investigator
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR) as assessed by the investigator
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:Maximum observed plasma concentration (Cmax) of BGB-15025
Time Frame:Predose up to 8 hours postdose
Safety Issue:
Description:
Measure:Minimum observed plasma concentration (Cmin) of BGB-15025
Time Frame:Predose up to 8 hours postdose
Safety Issue:
Description:
Measure:Time to maximum plasma concentration (Tmax) of BGB-15025
Time Frame:Predose up to 8 hours postdose
Safety Issue:
Description:
Measure:Half-life of (t1/2) of BGB-15025
Time Frame:Predose up to 8 hours postdose
Safety Issue:
Description:
Measure:Area under the concentration-time curve (AUC) of BGB-15025
Time Frame:Predose up to 8 hours postdose
Safety Issue:
Description:
Measure:Apparent clearance (CL/F) of BGB-15025
Time Frame:Predose up to 8 hours postdose
Safety Issue:
Description:
Measure:Apparent volume of distribution (Vz/F) of BGB-15025
Time Frame:Predose up to 8 hours postdose
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BeiGene

Last Updated

March 25, 2021