This is a first-in-human (FIH), open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-53038 as monotherapy in participants with advanced or metastatic solid tumors harboring KRAS mutations or amplification, as well as when used in combination with tislelizumab (also known as BGB-A317) in participants with nonsquamous non-small cell lung cancer (NSCLC) and used in combination with cetuximab in participants with colorectal cancer (CRC). The study consists of 2 phases: Phase 1a Dose Escalation and Safety Expansion and Phase 1b Dose Expansion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
514
Administered orally
administered by intravenous infusion
administered by intravenous infusion
Usc Norris Comprehensive Cancer Center (Nccc)
Los Angeles, California, United States
RECRUITINGUniversity of Kansas Medical Center Research Institute
Kansas City, Kansas, United States
RECRUITINGSidney Kimmel Comprehensive Cancer At Johns Hopkins
Baltimore, Maryland, United States
RECRUITINGThe University of Texas Md Anderson Cancer Center
Houston, Texas, United States
RECRUITINGBlacktown Cancer and Haematology Centre
Blacktown, New South Wales, Australia
RECRUITINGMonash Health
Clayton, Victoria, Australia
RECRUITINGPeter Maccallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGLinear Clinical Research
Nedlands, Western Australia, Australia
RECRUITINGCancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITING...and 8 more locations
Phase 1a: Number of Participants Experiencing Adverse Events (AEs)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) characterized by type, frequency, severity (as graded by the National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCICTCAE\] Version \[v\] 5.0), timing, seriousness, and relationship to study drug(s); and adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria
Time frame: Up to approximately 2 years
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-53038
defined as the highest dose at which 30% of the participants experienced a DLT or the highest dose administered, respectively.
Time frame: Up to approximately 2 years
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-53038
The potential RDFE(s) of BGB-53038 as monotherapy or in combination with other antitumor therapies (tislelizumab or cetuximab) will be determined based on the totality of safety, tolerability, pharmacokinetics (PK), pharmacodynamics, preliminary antitumor activity, and any other relevant data, as available.
Time frame: Up to approximately 2 years
Phase 1b: Overall Response Rate (ORR)
ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) assessed by the investigator using RECIST v1.1
Time frame: Up to approximately 2 years
Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-53038
The RP2D of BGB-53038 as monotherapy or in combination with other antitumor therapies (tislelizumab or cetuximab) will be determined based on safety, long-term tolerability, PK, preliminary antitumor activity, and any other relevant data, as available
Time frame: Up to approximately 2 years
Phase 1a: Single-dose and steady-state area under the concentration-time curve (AUC) of BGB-53038
Time frame: Up to approximately 2 years
Phase 1a: Single-dose and steady-state Half-life (t1/2) of BGB-53038
Time frame: Up to approximately 2 years
Phase 1a: Single-dose and steady-state maximum observed plasma concentration (Cmax) of BGB-53038
Time frame: Up to approximately 2 years
Phase 1a: Single-dose and steady-state trough concentration (Ctrough) of BGB-53038
Time frame: Up to approximately 2 years
Phase 1b: ORR
ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) assessed by the investigator using RECIST v1.1.
Time frame: Up to approximately 2 years
Duration of Response (DOR)
DOR is defined as the time from the first determination of an objective response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.
Time frame: Up to approximately 2 years
Time to Response (TRR)
defined as the time from the date of first dose of study drug to first documentation of response as assessed by the investigator per RECIST v1.1
Time frame: Up to approximately 2 years
Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve CR, PR, or stable disease (SD) lasting ≥ 24 weeks as assessed by the investigator per RECIST v1.1
Time frame: Up to approximately 2 years
Progression Free Survival (PFS)
PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first.
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Time frame: Up to approximately 2 years
Phase 1b: Overall Survival (OS)
defined as the time from the date of first dose of study drug until the date of death from any cause
Time frame: Up to approximately 2 years
Phase 1b: Number of Participants Experiencing Adverse Events (AEs)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) characterized by type, frequency, severity (as graded by the NCI-CTCAE v5.0), timing, seriousness, and relationship to study drug(s)
Time frame: Up to approximately 2 years
Plasma concentrations of BGB-53038
Time frame: Up to approximately 2 years