A Phase 1a/1b Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-53038, a Pan-KRAS Inhibitor, as Monotherapy or in Combinations in Patients With Advanced or Metastatic Solid Tumors With KRAS Mutations or Amplifications
Status: Recruiting
Location: See all (20) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY
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.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: t
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• Must sign a written ICF; and understand and agree to comply with the requirements of the study and the schedule of activities.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• 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
• Able to provide an archived tumor tissue sample or fresh biopsy sample.
• ≥ 1 measurable lesion per RECIST v1.1.
• Adequate organ function.
• 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
• 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).
Locations
United States
California
Usc Norris Comprehensive Cancer Center (Nccc)
RECRUITING
Los Angeles
Kansas
University of Kansas Medical Center Research Institute
RECRUITING
Kansas City
Maryland
Sidney Kimmel Comprehensive Cancer At Johns Hopkins
RECRUITING
Baltimore
Texas
The University of Texas Md Anderson Cancer Center
RECRUITING
Houston
Other Locations
Australia
Blacktown Cancer and Haematology Centre
NOT_YET_RECRUITING
Blacktown
Monash Health
RECRUITING
Clayton
Peter Maccallum Cancer Centre
RECRUITING
Melbourne
Linear Clinical Research
RECRUITING
Nedlands
China
Beijing Cancer Hospital
RECRUITING
Beijing
Cancer Hospital Chinese Academy of Medical Sciences
RECRUITING
Beijing
Shanxi Provincial Cancer Hospital
RECRUITING
Taiyuan
New Zealand
Auckland City Hospital
RECRUITING
Auckland
Republic of Korea
Seoul National University Bundang Hospital
RECRUITING
Bundanggu Seongnamsi
Samsung Medical Center
RECRUITING
Gangnamgu
Severance Hospital Yonsei University Health System
RECRUITING
Seodaemungu
Seoul National University Hospital
NOT_YET_RECRUITING
Seoul
Asan Medical Center
RECRUITING
Songpagu
Spain
Hospital Universitario Vall Dhebron
NOT_YET_RECRUITING
Barcelona
Start Madrid Fundacion Jimenez Diaz
NOT_YET_RECRUITING
Madrid
Hospital Clinico Universitario de Valencia Incliva
NOT_YET_RECRUITING
Valencia
Contact Information
Primary
Study Director
clinicaltrials@beigene.com
1.877.828.5568
Time Frame
Start Date:2024-11-26
Estimated Completion Date:2026-12
Participants
Target number of participants:514
Treatments
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.
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.
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.
Experimental: Phase 1b: Part D (Monotherapy Dose Expansion)
Participants will be enrolled to receive the RDFE(s) of BGB-53038 monotherapy
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.