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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

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

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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