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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  1. Must sign a written ICF; and understand and agree to comply with the requirements of the study and the schedule of activities. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1. 3. Participants must have evidence of a KRAS mutation or wild-type amplification (copy number ≥ 8) based on testing of either tumor tissue or liquid biopsy (blood or plasma) as determined by local laboratory 4. Able to provide an archived tumor tissue sample or fresh biopsy sample. 5. ≥ 1 measurable lesion per RECIST v1.1. 6. Adequate organ function. 7. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, for > 7 days after the last dose of BGB-53038, > 120 days after the last dose of tislelizumab, or > 2 months after the last dose of cetuximab, whichever is later 8. Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study treatment period and for ≥ 4 months after the last dose of study drug(s).

Exclusion Criteria

  1. Participants with tumors harboring KRAS G12R mutation. 2. Participants who have prior therapy with other anti-RAS treatment, including, but not limited to, therapy targeting specific KRAS allele mutation inhibitors, pan-KRAS inhibitors, and other pan-RAS inhibitors 3. Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis. Participants with a history of treated and, at the time of screening, stable CNS metastases are eligible, provided they meet select criteria. 4. Any malignancy ≤ 2 years before the first dose of study treatment(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). 5. Participants with untreated chronic hepatitis B or chronic HBV carriers with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) at screening. Participants with active hepatitis C. 6. Participants with clinically significant infections (including tuberculosis infection) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study treatment. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1a: Part A (Monotherapy Dose Escalation) 		Sequential cohorts will be evaluated to determine the Recommended Dose for Expansion (RDFE) of BGB-53038 as a monotherapy.
  • Drug: BGB-53038
    Administered orally
Experimental
Phase 1a: Part B (Monotherapy Safety Expansion) 		Participants will be enrolled at dose levels determined in Part A with the Safety Monitoring Committee to confirm the final RDFE(s) for BGB-53038 monotherapy.
  • Drug: BGB-53038
    Administered orally
Experimental
Phase 1a: Part C (Combination Therapy Dose Escalation) 		Sequential cohorts with increasing doses will be evaluated to determine the RDFE(s) for BGB-53038 in combination with tislelizumab or cetuximab.
  • Drug: BGB-53038
    Administered orally
  • Drug: Tislelizumab
    administered by intravenous infusion
    Other names:
    • Tevimbra
  • Drug: Cetuximab
    administered by intravenous infusion
Experimental
Phase 1b: Part D (Monotherapy Dose Expansion) 		Participants will be enrolled to receive the RDFE(s) of BGB-53038 monotherapy
  • Drug: BGB-53038
    Administered orally
Experimental
Phase 1b: Part E (Combination Therapy Dose Expansion) 		Participants will be enrolled to receive BGB-53038 at the RDFE(s) as determined in Part C of Phase 1a in combination with tislelizumab and in combination with cetuximab, respectively.
  • Drug: BGB-53038
    Administered orally
  • Drug: Tislelizumab
    administered by intravenous infusion
    Other names:
    • Tevimbra
  • Drug: Cetuximab
    administered by intravenous infusion

Recruiting Locations

University of Kansas Medical Center Research Institute
Kansas City, Kansas 66160-8500

More Details

Status
Recruiting
Sponsor
BeiGene

Study Contact

Study Director
1.877.828.5568
clinicaltrials@beigene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.