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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


2024-11-26


2026-12


2026-12


177

Study Overview

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

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.

N/A

  • 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
  • DRUG: BGB-53038
  • DRUG: Tislelizumab
  • DRUG: Cetuximab
  • BGB-53038-101
  • 2024-514704-13-00 (CTIS Identifier) (CTIS: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates Results Reporting Dates Study Record Updates

2024-09-03  

N/A  

2025-05-02  

2024-09-03  

N/A  

2025-05-06  

2024-09-05  

N/A  

2025-05  

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment


Allocation:
Randomized


Interventional Model:
Parallel


Masking:
None


Arms and Interventions

Participant Group/ArmIntervention/Treatment
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

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

DRUG: Cetuximab

  • administered by intravenous infusion
Primary Outcome MeasuresMeasure DescriptionTime Frame
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) criteriaUp to approximately 2 years
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-53038defined as the highest dose at which 30% of the participants experienced a DLT or the highest dose administered, respectively.Up to approximately 2 years
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-53038The 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.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 v1.1Up to approximately 2 years
Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-53038The 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 availableUp to approximately 2 years
Secondary Outcome MeasuresMeasure DescriptionTime Frame
Phase 1a: Single-dose and steady-state area under the concentration-time curve (AUC) of BGB-53038Up to approximately 2 years
Phase 1a: Single-dose and steady-state Half-life (t1/2) of BGB-53038Up to approximately 2 years
Phase 1a: Single-dose and steady-state maximum observed plasma concentration (Cmax) of BGB-53038Up to approximately 2 years
Phase 1a: Single-dose and steady-state trough concentration (Ctrough) of BGB-53038Up to approximately 2 years
Phase 1b: ORRORR 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.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.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 v1.1Up 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 v1.1Up 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.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 causeUp 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)Up to approximately 2 years
Plasma concentrations of BGB-53038Up to approximately 2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Study Director

Phone Number: 1.877.828.5568

Email: clinicaltrials@beigene.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:
1

    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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.


    • STUDY_DIRECTOR: Study Director, BeiGene

    Publications

    The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

    General Publications

    No publications available