This is a First in Human (FIH) Phase 1, multicenter, open label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-30813 as monotherapy or in combination with tislelizumab in participants with advanced or metastatic solid tumors. The study will be conducted in 2 parts: Phase 1a dose escalation and Phase 1b dose expansion.
This study will test whether taking BGB-30813 alone or with tislelizumab can help treat patients with cancer that has spread throughout the body or is locally advanced. The two main goals of the study are to ensure that the treatments are safe by monitoring side effects and to determine the number of participants who respond well to treatment either partially or completely. The combination of BGB-30813 with other drugs that target immune checkpoints may work together to stop or prevent cancer activity. Approximately 200 participants will participate. In the first part of the study, participants will be given different doses of BGB-30813 either alone or with tislelizumab to find the dose that is best tolerated. BGB-30813 will be given orally and tislelizumab will be given through a vein. In the second part of the study, the selected dose of BGB-30813, either alone or with tislelizumab, will be given to a larger number of participants from different parts of the world to see if the treatments can improve the signs and symptoms of their cancer. Treatments will continue until participants are no longer considered to be receiving benefits, have unacceptable side effects, or withdraw consent.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
44
Specified dose administered on specified days
Specified dose administered on specified days
Hackensack University Medical Center
Hackensack, New Jersey, United States
Md Anderson Cancer Center
Houston, Texas, United States
Next Oncology
San Antonio, Texas, United States
Phase 1a: Dose Escalation: Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Dose-Limiting Toxicities (DLTs)
Number of participants experiencing AEs and SAEs, including physical examination findings, electrocardiograms (ECGs), and lab assessments as needed; and AEs meeting protocol-defined DLT criteria.
Time frame: From the first dose of study drug(s) to 30 days after the last dose; approximately 6 months
Phase 1a: Dose Escalation: The Maximum Tolerated Dose (MTD) and Maximum Administered Dose (MAD)
The MTD or MAD is defined as the highest dose at which 30% of participants experience a DLT or the highest dose administered, respectively.
Time frame: Up to approximately 6 months
Phase 1a and 1b: Recommended dose(s) for Expansion (RDFE[s]) of BGB-30813 Alone or in Combination with Tislelizumab
The RDFE(s) of BGB-30813 alone or in combination with tislelizumab, determined based upon the MTD or MAD and other relevant data.
Time frame: Up to approximately 6 months
Phase 1b: Dose Expansion: Overall Response Rate (ORR) as Determined by the Investigator
ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) as determined from tumor assessments by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Up to approximately 12 months
Phase 1a: Dose Escalation: ORR as Determined by the Investigator
ORR is defined as the percentage of participants who had confirmed CR or PR as determined from tumor assessments by the investigator per RECIST version 1.1
Time frame: Up to approximately 12 months
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Monash Health
Clayton, Victoria, Australia
Peter Maccallum Cancer Centre
Melbourne, Victoria, Australia
Linear Clinical Research
Nedlands, Western Australia, Australia
Jinan Central Hospital
Jinan, Shandong, China
Shandong Provincial Hospital
Jinan, Shandong, China
Shandong Cancer Hospital
Jinan, Shandong, China
Hospital Universitario Vall Dhebron
Barcelona, Spain
...and 1 more locations
Phase 1a: Dose Escalation: Maximum Observed Plasma Concentration (Cmax) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab
Time frame: Up to approximately 6 months
Phase 1a: Dose Escalation: Observed Plasma Trough Concentration (Ctrough) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab
Time frame: Up to approximately 6 months
Phase 1a: Dose Escalation: Area under the concentration-time curve (AUC) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab
Time frame: Up to approximately 6 months
Phase 1a: Dose Escalation: Half-life (t1/2) Of BGB-30813 and Metabolite BGB-33481 Alone and in Combination with Tislelizumab
Time frame: Up to approximately 6 months
Phase 1b: Dose Expansion: Number of Participants Experiencing AEs and SAEs
Number of participants experiencing AEs and SAEs, including physical examination findings, ECGs, and lab assessments as needed.
Time frame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 6 months
Phase 1b: Dose Expansion: Duration of Response (DOR)
DOR is defined as the time from the first determination of an overall response assessed by the investigator using RECIST v1.1, until the first documentation of disease progression or death, whichever comes first.
Time frame: Up to approximately 12 months
Phase 1b: Dose Expansion: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with best overall response (BOR) of complete Response (CR), Partial Response (PR), or stable disease assessed by the investigator using RECIST v1.1.
Time frame: Up to approximately 12 months
Phase 1b: Dose Expansion: Progression Free Survival (PFS)
PFS is defined as the time from the date of the first dose of study drugs to the date of the first documentation of disease progression assessed by the investigator using RECIST v1.1 or death, whichever occurs first.
Time frame: Up to approximately 12 months
Phase 1b: Dose Expansion: Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants with BOR of confirmed CR, PR, or stable disease lasting ≥ 24 weeks as assessed by the investigator using RECIST v1.1.
Time frame: Up to approximately 12 months
Phase 1b: Dose Expansion: Plasma concentrations of BGB-30813, and its metabolite, BGB-33481
Time frame: Up to approximately 6 months