A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Selected Advanced or Metastatic Solid Tumors
Summary
This is a first-in-human (FIH) clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of BGB-B2033 administered as monotherapy and in combination with tislelizumab, with or without bevacizumab. The study will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP)-producing gastric cancer (GC), extragonadal yolk sac tumors/non-dysgerminomas, or glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC).
Arms & interventions
- DrugBGB-B2033
Administered by intravenous infusion
- DrugTislelizumab
Administered by intravenous infusion
- DrugBevacizumab
Administered by intravenous infusion
Outcome measures
Primary
Part A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0/American Society for Transplantation and Cellular Therapy \[ASTCT\] for cytokine release syndrome \[CRS\] and immune effector cell-associated neurotoxicity syndrome \[ICANS\]), timing, seriousness, and relationship to study therapy; assessment of adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria
Time frame: Up to approximately 2 years
Part A and B: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033
The MTD or MAD is defined as the highest dose that is tolerable or the highest dose administered, respectively.
Time frame: Up to approximately 2 years
Part A and B: Recommended Phase 2 dose (RP2D) of BGB-B2033
The RP2D(s) will be determined based on a biologically effective dose by taking the totality of available preclinical and clinical data, including safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity, into consideration
Time frame: Up to approximately 2 years
Part C and D: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC)
ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) using Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
Time frame: Up to approximately 2 years
Secondary
Part A and B: Overall Response Rate (ORR) as assessed by the investigator
Time frame: Up to approximately 2 years
Part A and B: Duration of Response (DOR) as assessed by the investigator
Time frame: Up to approximately 2 years
Part A and B: Disease Control Rate (DCR) as assessed by the investigator
Time frame: Up to approximately 2 years
Part A and B: Progression Free Survival (PFS) as assessed by the investigator
Time frame: Up to approximately 2 years
Part A and B: Serum concentration of of BGB-B2033
Time frame: Up to approximately 2 years
Part A and B: Number of participants with anti-drug antibodies (ADAs) to BGB-B2033
Time frame: Up to approximately 2 years
Part C and D: Overall Response Rate (ORR) as assessed by the investigator
Time frame: Up to approximately 2 years
Part C and D: Duration of Response (DOR) as assessed by the investigator and IRC
Time frame: Up to approximately 2 years
Part C and D: Progression Free Survival (PFS) as assessed by the investigator and IRC
Time frame: Up to approximately 2 years
Part C and D: Overall Survival (OS)
Time frame: Up to approximately 2 years
Part C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to approximately 2 years
Eligibility criteria
Study locations (7)
City of Hope Phoenix Cancer Center
Goodyear, Arizona, 85338
City of Hope National Medical Center
Duarte, California, 91010-3012
City of Hope Chicago Cancer Center
Zion, Illinois, 60099
Memorial Sloan Kettering Cancer Center Mskcc
New York, New York, 10065-6800
Upmc Hillman Cancer Center(Univ of Pittsburgh)
Pittsburgh, Pennsylvania, 15232-1309
Scri Oncology Partners
Nashville, Tennessee, 37203-1503
The University of Texas Md Anderson Cancer Center
Houston, Texas, 77030-4009