A First-in-Human Study Investigating BG-85738 Alone or in Combination With Other Antitumor Agents in Patients With Advanced or Metastatic Solid Tumors With Rat Sarcoma Virus (RAS) Mutations

A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-85738, Alone or in Combination With Other Antitumor Agents, in Patients With Advanced or Metastatic Solid Tumors With RAS Mutations

The purpose of this study is to test if the BG-85738 is safe and if it works in patients with advanced solid tumors with RAS mutations when it is given on its own and in combination.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; RAS Mutation
• Intervention / Treatment: Drug: Cetuximab; Drug: Tislelizumab; Drug: BG-85738

Detailed Description

A solid tumor is an abnormal mass of tissue caused by the uncontrolled growth of cells which can develop in organs, bones, or soft tissues. An advanced or metastatic solid tumor is a cancer that has either grown into nearby tissues ("advanced") or spread to distant parts of the body ("metastatic").

Many types of solid cancers have a change (mutation) in a gene called RAS gene. In normal cells, RAS proteins work by controlling when cells grow and divide. RAS mutations in cancer cells might lead to hyperactivation of the RAS proteins, which can result in continuous and uncontrolled growth of cancer cells. BG-85738 is a new experimental medicine that has been designed to block RAS proteins that are hyperactive.

The purpose of this study is to test whether BG-85738 is safe and if it can help to treat adults with advanced or metastatic solid tumors with a RAS mutation. This study has two parts, one called dose escalation, and one called safety expansion. During the dose escalation part, the study doctors will test different doses of the study drug[s] to find the recommended dose that people can take without having serious side effects.

During the dose expansion part, the study doctors will test the study drug in a larger number of people using the dose[s] identified from dose escalation.

The study will enroll patients at multiple centers worldwide who have been diagnosed with an advanced solid tumor that has a RAS gene mutation. The overall time to participate in this study is approximately 13 to 24 months. Participants will make regular visits to the clinic for treatment, health checks, blood tests, and for tumor and imaging tests.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 877-828-5568; Email: clinicaltrials@beonemed.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if they meet all the following criteria:

• Participants must sign the informed consent form and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Participants must be ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place, whichever is older), at the time of signing the ICF.
• Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors and meet study part and cohort-specific criteria
• Participants must have evidence of a RAS mutation defined as a nonsynonymous mutation in Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), or Harvey rat sarcoma viral oncogene homolog (HRAS) at codons 12, 13, or 61 (G12, G13, or Q61), based on testing of either tumor tissue or liquid biopsy (blood or plasma) as determined by the local laboratory

Exclusion Criteria:

Participants are excluded from the study if they meet any of the following criteria:

• Participants who have prior RAS-targeted therapy, including, but not limited to, KRAS mutation-specific inhibitors (with the exception of participants with NSCLC and colorectal cancer who received a G12C inhibitor), pan-KRAS inhibitors, and pan-RAS inhibitors.
• Participants who have a history of severe allergic reactions or hypersensitivity to the active ingredient and excipients of study treatment.
• Participants who are unable to comply with the requirements of the protocol.
• Participants with active leptomeningeal disease or uncontrolled, untreated brain metastases
• Participants with any malignancy ≤ 3 years before the first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
• Participants with active hepatitis C.
• Participants with medical history of untreated Human Immunodeficiency Virus infection.

Note: Other protocol defined criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a: Part A- Monotherapy Dose escalation and safety; Ascending dose levels of BG-85738 will be evaluated as monotherapy in participants with advanced or metastatic solid tumors with RAS mutations.	Drug: BG-85738; Administered orally
Experimental: Phase 1a: Part B - Combination therapy Dose escalation; Sequential dose levels of BG-85738, selected based on Part A data, will be evaluated in combination with tislelizumab or in combination with cetuximab.	Drug: Cetuximab; Administered intravenously; Drug: Tislelizumab; Administered intravenously; Drug: BG-85738; Administered orally
Experimental: Phase 1b: Part C- Monotherapy dose expansion; Participants with selected tumor types will receive BG-85738 monotherapy at the RDFE(s) identified in Phase 1a Part A.	Drug: BG-85738; Administered orally
Experimental: Phase 1b: Part D - Combination therapy dose expansion; Participants with select tumor types will receive BG-85738 in combination with tislelizumab or in combination with cetuximab at the RDFE(s) identified in Phase 1a Part B	Drug: Cetuximab; Administered intravenously; Drug: Tislelizumab; Administered intravenously; Drug: BG-85738; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a (Part A and Part B): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporarily associated with the use of study treatment, whether considered related to study treatment or not. An SAE is any untoward medical occurrence that, at any dose,; Results in death; Is life-threatening; Requires hospitalization or prolongation of existing hospitalization; Results in disability/incapacity; Is congenital anomaly/birth defect; Is considered a significant medical AE by the investigator based on medical judgement	From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
Phase 1a (Parts A and B): Number of Participants with Dose Limiting Toxicity (DLT)		Up to approximately 1 month
Phase 1a (Parts A and B): Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-85738 as monotherapy or in combination with other antitumor agents	MTD is defined as the highest dose level with the target DLT closest but not exceeding 0.33. MAD is defined as the maximum administered dose and it is used when MTD is not reached.	Up to approximately 1 month
Phase 1a: Recommended Dose for Expansion (RDFE) of BG-85738		Up to approximately 1 month
Part 1b (Parts C and D): Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR).; CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm.; PR: A ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to approximately 24 months
Phase 1b Dose Expansion: Recommended Phase 2 dose (RP2D) of BG-85738		Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a (Part A and Part B): Terminal Half Life (t1/2) of BG-85738		Up to approximately 2 months
Phase 1a (Part A and Part B): Area Under the Plasma Concentration-Time Curve (AUC) of BG-85738		Up to approximately 2 months
Phase 1a (Part A and Part B): Minimum Observed Serum Concentration (Ctrough) of BG-85738		Up to approximately 2 months
Phase 1a (Part A and Part B): Maximum Observed Plasma Concentration (Cmax) of BG-85738		Up to approximately 2 months
Phase 1a (Part A and Part B): Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR).; CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm.; PR: A ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to approximately 24 months
Phase 1b (Parts C and D): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporarily associated with the use of study treatment, whether considered related to study treatment or not. An SAE is any untoward medical occurrence that, at any dose,; Results in death; Is life-threatening; Requires hospitalization or prolongation of existing hospitalization; Results in disability/incapacity; Is congenital anomaly/birth defect; Is considered a significant medical AE by the investigator based on medical judgement	From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 24 months
Phase 1b (Part C and D): Duration of response (DOR)	DOR is defined as the time from the first determination of an overall response until the first documentation of progression or death, whichever comes first.	Up to approximately 24 months
Phase 1b (Part C and D): Disease control rate (DCR)	DCR is defined as the percentage of participants with best of response of a CR, PR, and stable disease.	Up to approximately 24 months
Phase 1b (Part C and D): Time to response (TTR)	TTR is defined as the time from date of the first dose of study treatment to the first overall response.	Up to approximately 24 months
Phase 1b (Part C and D): Progression-free survival (PFS) as assessed by the investigator	PFS is defined as the time from the date of the first dose of study treatment to the date of the first documentation of progressive disease or death, whichever occurs first, as assessed by the investigator per RECIST v1.1	Up to approximately 24 months
Phase 1b (Part C): Intracranial Objective Response Rate (iORR)	Intracranial objective response rate is defined as the percentage of patients with a best overall Intracranial response of CR or PR according to modified (m)RECIST v1.1 per Investigator assessment.	Up to approximately 24 months
Phase 1b (Part C): Intracranial Duration of Response (iDOR)	iDOR is defined as the time from the first determination of an overall intracranial response until the first documentation of progression or death, whichever comes first, with intracranial assessments by the investigator via modified RECIST v1.1 adapted for brain metastases.	Up to approximately 24 months
Phase 1b (Part C): Intracranial Progression-free survival (iPFS) as determined from tumor assessments by the investigator	iPFS is defined as the time from the date of the first dose of study treatment to the date of the first documentation of progressive disease or death, whichever occurs first. PFS is determined from tumor assessments by the investigator per a modified RECIST v1.1 adapted for brain metastases	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): September 4, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: July 30, 2026
• First Submitted That Met QC Criteria: July 30, 2026
• First Posted (Actual): August 4, 2026

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: July 30, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Cetuximab; tislelizumab
• Other Study ID Numbers: BG-85738-101; 2026-526560-20-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No