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
NCT Number: NCT06585488
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: 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
Sponsor: BeiGene
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 177
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12
Completion Date: 2026-12

Summary:
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.

Primary Outcome Measures: 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) criteria, Up to approximately 2 years|Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-53038, defined 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-53038, The 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 v1.1, Up to approximately 2 years|Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-53038, The 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 available, Up to approximately 2 years
Secondary Outcome Measures: Phase 1a: Single-dose and steady-state area under the concentration-time curve (AUC) of BGB-53038, Up to approximately 2 years|Phase 1a: Single-dose and steady-state Half-life (t1/2) of BGB-53038, Up to approximately 2 years|Phase 1a: Single-dose and steady-state maximum observed plasma concentration (Cmax) of BGB-53038, Up to approximately 2 years|Phase 1a: Single-dose and steady-state trough concentration (Ctrough) of BGB-53038, Up to approximately 2 years|Phase 1b: 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 v1.1., 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 v1.1, Up 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 v1.1, Up 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 Surival (OS), defined as the time from the date of first dose of study drug until the date of death from any cause, Up 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-53038, Up to approximately 2 years