A First-in-human Study of BGB-53038, a Pan-KRAS Inhibitor, Alone or in Combinations in Participants With Advanced or Metastatic Solid Tumors With KRAS Mutations or Amplification

Stopped early · Phase 1

Conditions studied: Metastatic Solid Tumors, Advanced Non-squamous Non-small-cell Lung Cancer, Advanced Colorectal Cancer, Advanced Pancreatic Ductal Adenocarcinoma, Advanced Gastric Cancer, Advanced Gastroesophageal Junction Cancer, Advanced Esophageal Adenocarcinoma

In brief

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.

Key facts

Study ID

NCT06585488

Run by

BeOne Medicines

People needed

47

Starts

2024-12-13

Expected to finish

2026-04-23

Last updated by the study team

2026-07-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• 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).

You may not qualify if…

• Participants with tumors harboring KRAS G12R mutation.
• 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
• 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.
• 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).
• 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.
• 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.

Where it is running

• Usc Norris Comprehensive Cancer Center (Nccc) — Los Angeles, California, United States
• University of Kansas Medical Center Research Institute — Kansas City, Kansas, United States
• Sidney Kimmel Comprehensive Cancer At Johns Hopkins — Baltimore, Maryland, United States
• The University of Texas Md Anderson Cancer Center — Houston, Texas, United States
• Blacktown Cancer and Haematology Centre — Blacktown, New South Wales, Australia
• Monash Health — Clayton, Victoria, Australia
• Peter Maccallum Cancer Centre — Melbourne, Victoria, Australia
• Linear Clinical Research — Nedlands, Western Australia, Australia
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China
• Beijing Cancer Hospital — Beijing, Beijing Municipality, China
• Shanxi Provincial Cancer Hospital — Taiyuan, Shanxi, China
• Auckland City Hospital — Auckland, New Zealand
• Seoul National University Bundang Hospital — Seongnam-si, Gyeonggi-do, South Korea
• Samsung Medical Center — GangnamGu, Seoul Teugbyeolsi, South Korea
• Severance Hospital Yonsei University Health System — SeodaemunGu, Seoul Teugbyeolsi, South Korea
• Seoul National University Hospital — Seoul, Seoul Teugbyeolsi, South Korea
• Asan Medical Center — SongpaGu, Seoul Teugbyeolsi, South Korea

Full record on ClinicalTrials.gov

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