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

Official title

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

Overview

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.

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.

Interventions

• Drug BG-85738
  Administered orally
• Drug Tislelizumab
  Administered intravenously
• Drug Cetuximab
  Administered intravenously

Primary outcome measures

• Phase 1a (Part A and Part B): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: 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) [Time frame: 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 [Time frame: Up to approximately 1 month]
• Phase 1a: Recommended Dose for Expansion (RDFE) of BG-85738 [Time frame: Up to approximately 1 month]
• Part 1b (Parts C and D): Overall Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Phase 1b Dose Expansion: Recommended Phase 2 dose (RP2D) of BG-85738 [Time frame: Up to approximately 24 months]

Secondary outcome measures (12)

• Phase 1a (Part A and Part B): Terminal Half Life (t1/2) of BG-85738 [Time frame: Up to approximately 2 months]
• Phase 1a (Part A and Part B): Area Under the Plasma Concentration-Time Curve (AUC) of BG-85738 [Time frame: Up to approximately 2 months]
• Phase 1a (Part A and Part B): Minimum Observed Serum Concentration (Ctrough) of BG-85738 [Time frame: Up to approximately 2 months]
• Phase 1a (Part A and Part B): Maximum Observed Plasma Concentration (Cmax) of BG-85738 [Time frame: Up to approximately 2 months]
• Phase 1a (Part A and Part B): Overall Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Phase 1b (Parts C and D): Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: 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) [Time frame: Up to approximately 24 months]
• Phase 1b (Part C and D): Disease control rate (DCR) [Time frame: Up to approximately 24 months]
• Phase 1b (Part C and D): Time to response (TTR) [Time frame: Up to approximately 24 months]
• Phase 1b (Part C and D): Progression-free survival (PFS) as assessed by the investigator [Time frame: Up to approximately 24 months]
• Phase 1b (Part C): Intracranial Objective Response Rate (iORR) [Time frame: Up to approximately 24 months]
• Phase 1b (Part C): Intracranial Duration of Response (iDOR) [Time frame: Up to approximately 24 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07746141 · BG-85738-101 · 2026-526560-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗