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Trial record 1 of 1 for:    NCT04215978
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Safety and Preliminary Effectiveness of BGB-A445 in Combination With Tislelizumab in Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04215978
Recruitment Status : Active, not recruiting
First Posted : January 2, 2020
Last Update Posted : January 12, 2024
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
The purpose of this study is to assess the safety and tolerability of BGB-A445 alone and in combination with tislelizumab in participants with advanced solid tumors; and to determine the maximum tolerated dose(s) (MTD) or maximum administered dose(s) (MAD) and recommended Phase 2 doses (RP2D) of BGB-A445 alone and in combination with tislelizumab.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Non Small Cell Lung Cancer Head and Neck Squamous Cell Carcinoma (HNSCC) Nasopharyngeal Carcinoma (NPC) Drug: BGB-A445 Drug: tislelizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 203 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of the Anti OX40 Agonist Monoclonal Antibody BGB-A445 in Combination With the Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors
Actual Study Start Date : January 30, 2020
Estimated Primary Completion Date : September 16, 2024
Estimated Study Completion Date : September 16, 2024


Arm Intervention/treatment
Experimental: Phase 1a: BGB-A445 Monotherapy
Dose Escalation Part A: Participants will receive intravenous (IV) infusion of BGB-A445 in sequential cohorts of approximately 8 increasing dose levels on day 1 of each 21-day cycle
Drug: BGB-A445
Administered as specified in the treatment arm

Experimental: Phase 1a: BGB-A445 + Tislelizumab Combination Therapy
Dose Escalation Part B: Participants will receive IV infusion of BGB-A445 in sequential cohorts of approximately 6 increasing dose levels plus 200mg tislelizumab on day 1 of each 21-day cycle
Drug: BGB-A445
Administered as specified in the treatment arm

Drug: tislelizumab
Administered as specified in the treatment arm
Other Name: BGB-A317

Experimental: Phase 1b:BGB-A445 Monotherapy
Dose Expansion Part A: Participants will receive recommended doses of IV BGB-A445 as determined from Phase 1a Dose Escalation; BGB-A445 will be evaluated in two tumor types
Drug: BGB-A445
Administered as specified in the treatment arm

Experimental: Phase 1b: BGB-A445 + Tislelizumab and Chemotherapy Combination Therapy
Dose Expansion Part B: Participants will receive recommended dose IV infusion of BGB-A445 plus 200mg tislelizumab and chemotherapy
Drug: BGB-A445
Administered as specified in the treatment arm

Drug: tislelizumab
Administered as specified in the treatment arm
Other Name: BGB-A317

Experimental: Phase 1b: BGB-A445 Monotherapy
Dose Expansion Part C: Participants will receive 1 dose level of BGB-A445
Drug: BGB-A445
Administered as specified in the treatment arm




Primary Outcome Measures :
  1. Phase 1a: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy ]
  2. Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy ]
  3. Phase 1a: Number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria [ Time Frame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy ]
  4. Phase 1a: Maximum Tolerated Dose (MTD) of BGB-A445 [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
    The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%

  5. Phase 1b: RP2D of BGB-A445 when Administered Alone [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
  6. Phase 1b: Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
    ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)


Secondary Outcome Measures :
  1. Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
  2. Phase 1a: Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
  3. Phase 1a: Disease-Control Rate (DCR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
  4. Phase 1a: Serum Concentration of BGB-A445 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  5. Phase 1a: Serum Concentration of tislelizumab [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  6. Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-A445 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  7. Phase 1a: Maximum Observed Plasma Concentration (Cmax) of tislelizumab [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  8. Phase 1a: Minimum Observed Plasma Concentration (Cmin) of BGB-A445 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  9. Phase 1a: Minimum Observed Plasma Concentration (Cmin) of tislelizumab [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  10. Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-A445 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  11. Phase 1a: Time to Maximum Plasma Concentration (Tmax) of tislelizumab [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  12. Phase 1a: Area Under the Concentration-Time Curve of 0-21 Days (AUC0-21d) of BGB-A445 [ Time Frame: 60 minutes predose up to 21 days postdose ]
  13. Phase 1a: Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
  14. Phase 1a: Immunogenic Responses to tislelizumab as assessed through the detection of antidrug antibodies [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
  15. Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
    Determined from investigator derived tumor assessments as per RECIST 1.1

  16. Phase 1b: Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
  17. Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]
  18. Phase 1b: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy ]
  19. Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy ]
  20. Phase 1b: Serum Concentration of BGB-A445 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  21. Phase 1b: Maximum Observed Plasma Concentration (Cmax) of BGB-A445 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  22. Phase 1b: Minimum Observed Plasma Concentration (Cmin) of BGB-A445 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  23. Phase 1b: Time to Maximum Plasma Concentration (Tmax) of BGB-A445 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  24. Phase 1b: Area Under the Concentration-Time Curve of 0-21 Days (AUC0-21d) of BGB-A445 [ Time Frame: 60 minutes predose up to 21 days postdose ]
  25. Phase 1b: Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies [ Time Frame: Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first ]


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

Key Inclusion Criteria:

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

  1. Enrollment will be limited to participants with advanced solid tumors for which there is clinical evidence of response to T cell based immuno-oncology agents (eg, anti PD 1) or other scientific evidence in support of an immunologically sensitive tumor type.
  2. Participant has not received prior therapy targeting OX40 or any other T cell agonist therapy (prior checkpoint inhibitor therapy is allowed)

    2. Phase 1b, the dose expansion phase, aims to include participants in specific tumor type cohorts who do not have access to standard systemic treatment, cannot tolerate it, or it is deemed inappropriate by the investigator. Cohort 1 focuses on non-small cell lung cancer (NSCLC) patients with advanced or metastatic disease, while Cohort 2 involves individuals with recurrent or metastatic head and neck squamous cell cancer (HNSCC). Cohort 3 includes participants with nasopharyngeal carcinoma (NPC), and Cohort 4 is for NSCLC patients with PD-L1 expression of at least 50%. Each cohort has specific eligibility criteria related to prior therapies, tumor characteristics, and treatment-free intervals.

    3. Has 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 4. Participants should be able to provide tumor tissue sample 5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 and a life expectancy of ≥ 6 months.

    6. Adequate organ function as indicated by the following laboratory values up to first dose of study drug

a. Participants must not have required blood transfusion or growth factor support ≤ 14 days before sample collection for the following:

  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 75 x 10^9/L
  • Hemoglobin ≥ 90 g/L

    b. Estimated glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2 determined by the Cockcroft-Gault formula without correction for body surface area (BSA)

  • The estimated GFR for participants with renal cell carcinoma must be ≥ 30 mL/min/1.73 m^2 by the Cockcroft-Gault formula

    c. Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for participants with Gilbert syndrome) d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN;

  • ≤ 5 x ULN for participants with hepatocellular carcinoma or liver metastases

Key Exclusion Criteria:

  1. Active leptomeningeal disease or uncontrolled brain metastasis. Participants with equivocal findings or with confirmed brain metastases are eligible for enrollment provided 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 or history of life-threatening toxicity related to prior immune therapy, with the following exceptions:

    1. Controlled type 1 diabetes
    2. Hypothyroidism (provided 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 (requires consultation with the medical monitor prior to enrollment)
  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. Any major surgical procedure occurring ≤ 28 days before the first dose of study drug(s). If surgical procedure occurs > 28 days, they must have recovered adequately from the toxicity

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): NCT04215978


Locations
Show Show 22 study locations
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Study Director BeiGene
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT04215978    
Other Study ID Numbers: BGB-A317-A445-101
First Posted: January 2, 2020    Key Record Dates
Last Update Posted: January 12, 2024
Last Verified: January 2024
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
Product Manufactured in and Exported from the U.S.: No
Keywords provided by BeiGene:
OX40
PD-1
Additional relevant MeSH terms:
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Carcinoma
Nasopharyngeal Carcinoma
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Nasopharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Tislelizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents