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.
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
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
Sequential
BG-85738
DrugAdministered orally
Tislelizumab
DrugAdministered intravenously
Cetuximab
DrugAdministered intravenously
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
Phase 1a (Parts A and B): Number of Participants with Dose Limiting Toxicity (DLT)
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.
Phase 1a: Recommended Dose for Expansion (RDFE) of BG-85738
Phase 1a (Part A and Part B): Terminal Half Life (t1/2) of BG-85738
Phase 1a (Part A and Part B): Area Under the Plasma Concentration-Time Curve (AUC) of BG-85738
Phase 1a (Part A and Part B): Minimum Observed Serum Concentration (Ctrough) of BG-85738
Phase 1a (Part A and Part B): Maximum Observed Plasma Concentration (Cmax) of BG-85738
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