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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 : Recruiting
First Posted : January 2, 2020
Last Update Posted : August 30, 2022
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
Phase 1a:Advanced Solid Tumors; Phase 1b: Non-small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC) Drug: BGB-A445 Drug: tislelizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 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 : June 30, 2024
Estimated Study Completion Date : September 30, 2024

Resource links provided by the National Library of Medicine


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 Combination Therapy
Dose Expansion Part B: Participants will receive recommended dose IV infusion of BGB-A445 plus 200mg tislelizumab to be evaluated in two tumor types
Drug: BGB-A445
Administered as specified in the treatment arm

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




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

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 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 (dose expansion): Participants in specific tumor type cohorts for whom standard systemic treatment is not available, not tolerated, or refused. Participant must not have received prior therapy targeting OX40 or any other T-cell agonist. Prior checkpoint inhibitor therapy is allowed. Note: Refused treatment not applicable in South Korea.

    1. Cohort 1 (NSCLC): Patients with histologically or cytologically confirmed stage IIIB, IIIC, or IV disease whose tumor is not amenable to local therapy with curative intent (ie. surgery or radiotherapy with or without chemotherapy), who have received ≥1 but no more than 3 lines of prior systemic therapy for advanced or metastatic disease. Patients who progressed within 6 months following completion of systemic therapy for local disease should have received a platinum-based agent. Patients who are eligible to receive targeted therapy (if actionable oncogenic driver mutations with locally approved therapy were identified [eg. EGFR, ALK or other]) must have received appropriate targeted therapy.
    2. Cohort 2 (HNSCC): Patients with histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell cancer whose tumor is not amenable to local therapy with curative intent (ie. surgery or radiotherapy with or without chemotherapy), and who have received ≥1 but no more than 3 lines of prior systemic therapy for recurrent or metastatic disease or progressed within 6 months following completion of systemic therapy for local disease.
  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 must be able to provide an archived formalin fixed paraffin embedded (FFPE) tumor tissue sample (block or approximately 15 freshly unstained FFPE slides) after the most recent line of therapy. If archival tissue is not available, fresh tumor biopsy is mandatory.

    a. Participants enrolled must provide baseline tumor tissue as outlined as well as be willing and medically fit to undergo mandatory on treatment biopsies with no excessive risk as judged by the investigator

  5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
  6. Adequate organ function as indicated by the following laboratory values up to first dose of study drug

    1. 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 ≥ 90g/L
    2. 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
    3. Serum total bilirubin ≤ 1.5 x ULN (< 3 x ULN for participants with Gilbert syndrome)
    4. 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 and/or complications from the intervention before the first dose of study drug(s).
  6. Any of the following cardiovascular risk factors:

    1. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before the first dose of study drug(s)
    2. Pulmonary embolism ≤ 28 days before the first dose of study drug(s)
    3. Any history of acute myocardial infarction ≤ 6 months before the first dose of study drug(s)
    4. Heart failure that meets the New York Heart Association Classification III or IV ≤ 6 months before the first dos6.e of study drug(s)
    5. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before the first dose of study drug(s)
    6. Any history of cerebrovascular accident ≤ 6 months before the first dose of study drug(s)
    7. Uncontrolled hypertension: systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg on repeated measurements that cannot be managed by standard antihypertension medications ≤ 28 days before the first dose of study drug(s)
    8. Any episode of syncope or seizure ≤ 28 days before the first dose of study drug(s)

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


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

Locations
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United States, Pennsylvania
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Australia, New South Wales
Blacktown Hospital Recruiting
Blacktown, New South Wales, Australia, 2146
Australia, Queensland
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia
Australia, Victoria
Monash Health Recruiting
Melbourne, Victoria, Australia, 3004
Peter MacCallum Cancer Center Recruiting
Melbourne, Victoria, Australia
Australia, Western Australia
Linear Clinical Research Recruiting
Perth, Western Australia, Australia, 6009
Korea, Republic of
National Cancer Centre Recruiting
Gyeonggi-do, Korea, Republic of, 10408
Cha Bundang Medical Centre, Cha University Recruiting
Gyeonggi-do, Korea, Republic of, 13496
The Catholic University of Korea, St Vincents Hospital Recruiting
Gyeonggi-do, Korea, Republic of, 16247
Seoul National University Bundang Hospital Recruiting
Gyeongju, Korea, Republic of, 13620
Severance Hospital Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 03722
New Zealand
Auckland City Hospital Recruiting
Grafton, New Zealand, 1023
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: August 30, 2022
Last Verified: August 2022
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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Squamous Cell Carcinoma of Head and Neck
Neoplasms
Neoplasms by Site
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Head and Neck Neoplasms