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

NCT ID: NCT06585488

Last Updated: 2026-02-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

514 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-26

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

BGB-53038

Intervention Type DRUG

Administered orally

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.

Group Type EXPERIMENTAL

BGB-53038

Intervention Type DRUG

Administered orally

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.

Group Type EXPERIMENTAL

BGB-53038

Intervention Type DRUG

Administered orally

Tislelizumab

Intervention Type DRUG

administered by intravenous infusion

Cetuximab

Intervention Type DRUG

administered by intravenous infusion

Phase 1b: Part D (Monotherapy Dose Expansion)

Participants will be enrolled to receive the RDFE(s) of BGB-53038 monotherapy

Group Type EXPERIMENTAL

BGB-53038

Intervention Type DRUG

Administered orally

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.

Group Type EXPERIMENTAL

BGB-53038

Intervention Type DRUG

Administered orally

Tislelizumab

Intervention Type DRUG

administered by intravenous infusion

Cetuximab

Intervention Type DRUG

administered by intravenous infusion

Interventions

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BGB-53038

Administered orally

Intervention Type DRUG

Tislelizumab

administered by intravenous infusion

Intervention Type DRUG

Cetuximab

administered by intravenous infusion

Intervention Type DRUG

Other Intervention Names

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Tevimbra

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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BeiGene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

BeiGene

Locations

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Usc Norris Comprehensive Cancer Center (Nccc)

Los Angeles, California, United States

Site Status RECRUITING

University of Kansas Medical Center Research Institute

Kansas City, Kansas, United States

Site Status RECRUITING

Sidney Kimmel Comprehensive Cancer At Johns Hopkins

Baltimore, Maryland, United States

Site Status RECRUITING

The University of Texas Md Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, Australia

Site Status RECRUITING

Monash Health

Clayton, Victoria, Australia

Site Status RECRUITING

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Linear Clinical Research

Nedlands, Western Australia, Australia

Site Status RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Shanxi Provincial Cancer Hospital

Taiyuan, Shanxi, China

Site Status RECRUITING

Auckland City Hospital

Auckland, , New Zealand

Site Status RECRUITING

Seoul National University Bundang Hospital

BundangGu SeongnamSi, Gyeonggi-do, South Korea

Site Status RECRUITING

Samsung Medical Center

GangnamGu, Seoul Teugbyeolsi, South Korea

Site Status RECRUITING

Severance Hospital Yonsei University Health System

SeodaemunGu, Seoul Teugbyeolsi, South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, South Korea

Site Status RECRUITING

Asan Medical Center

SongpaGu, Seoul Teugbyeolsi, South Korea

Site Status RECRUITING

Start Madrid Fundacion Jimenez Diaz

Madrid, , Spain

Site Status RECRUITING

Countries

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United States Australia China New Zealand South Korea Spain

Central Contacts

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Study Director

Role: CONTACT

1.877.828.5568

Other Identifiers

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2024-514704-13-00

Identifier Type: CTIS

Identifier Source: secondary_id

BGB-53038-101

Identifier Type: -

Identifier Source: org_study_id

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