A First-in-Human Study of BG-C0902 Alone and in Combination With Other Therapeutic Agents in Patients With Advanced Solid Tumors

Official title

A Phase 1a/b Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-C0902, an Antibody-Drug Conjugate Targeting Epidermal Growth Factor Receptor (EGFR) × Mesenchymal-Epithelial Transition (MET), Alone and in Combination With Other Therapeutic Agents in Patients With Advanced Solid Tumors

Overview

This study is a first-in-human (FIH), Phase 1a/1b study of BG-C0902, a fully humanized anti-epidermal growth factor receptor (EGFR) and anti-mesenchymal-epithelial transition (MET) antibody, conjugated via an enzymatically cleavable linker to a topoisomerase 1 (TOPO1) inhibitor payload. The study aims to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C0902 in participants with advanced solid tumors. The study will be conducted in 2 phases: Phase 1a (dose escalation and safety expansion) and Phase 1b (dose expansion).

Detailed description

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Interventions

• Drug BG-C0902
  Administered by intravenous infusion

Primary outcome measures

• Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Approximately 24 Months]
• Phase 1a: Number of Participants with Dose Limiting Toxicities (DLTs) [Time frame: Approximately 21 Days]
• Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C0902 [Time frame: Approximately 24 Months]
• Phase 1a: Recommended dose(s) for Expansion (RDFE) of BG-C0902 [Time frame: Approximately 24 Months]
• Phase 1b: Recommended Phase 2 Dose (RP2D) of BG-C0902 as Monotherapy [Time frame: Approximately 24 Months]
• Phase 1b: Overall Response Rate (ORR) [Time frame: Approximately 24 Months]

Secondary outcome measures (11)

• Phase 1a: ORR [Time frame: Approximately 24 Months]
• Phase 1a and 1b: Duration of Response (DOR) [Time frame: Approximately 24 Months]
• Phase 1a and 1b: Disease Control Rate (DCR) [Time frame: Approximately 24 Months]
• Phase 1b: Progression-free Survival (PFS) [Time frame: Approximately 24 Months]
• Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Approximately 24 Months]
• Phase 1a and 1b: Area under the Concentration-time Curve (AUC) of BG-C0902, Total Antibody, and Payload [Time frame: Two times in the first three months]
• Phase 1a and 1b: Maximum Observed Plasma Concentration (Cmax) of BG-C0902, Total Antibody, and Payload [Time frame: Two times in the first three months]
• Phase 1a and 1b: Time to Maximum Concentration (Tmax) of BG-C0902, Total Antibody, and Payload [Time frame: Two times in the first three months]
• Phase 1a and 1b: Half-life (t1/2) of BG-C0902, Total Antibody, and Payload [Time frame: Two times in the first three months]
• Phase 1a and 1b: Volume of Distribution (Vd) of BG-C0902, Total Antibody, and Payload [Time frame: Two times in the first three months]
• Phase 1a and 1b: Number of Participants with Anti-drug Antibodies (ADAs) to BG-C0902 [Time frame: Approximately 24 Months]

Eligibility criteria

Inclusion criteria

• Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors not amenable to therapy with curative intent or for whom treatment is not available or not tolerated.
• Participants must be able to provide archival tissue formalin-fixed paraffin-embedded (FFPE) block containing tumor tissue or approximately 10 to 15 freshly cut unstained FFPE slides) or recently obtained fresh tumor biopsy samples at screening.
• Participants must have ≥ 1 measurable lesion as assessed by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1, as assessed ≤ 14 days before the first dose of study drug.
• Adequate bone marrow and organ function as indicated by the following laboratory values ≤ 14 days before the first dose of study drug
• Female participants of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 7 months after the last dose of study drug. They must also have a negative serum pregnancy test result ≤ 3 days before the first dose of study drug.
• Nonsterile male participants must be willing to use a highly effective method of birth control and refrain from sperm donation for the duration of the study and for ≥ 4 months after the last dose of study drug.

Exclusion criteria

• History of severe allergic reactions or hypersensitivity to BG-T187 or other monoclonal antibodies, or to the active ingredient and excipients of the study drug or camptothecins.
• For Phase 1a Part B Safety Expansion and Phase 1b only: Prior treatment with an EGFR-targeting ADC or mesenchymal-epithelial transition (MET)-targeting antibody-drug conjugate (ADC), or any ADC with topoisomerase I (TOPO1) inhibitor payload.
• Active leptomeningeal disease or uncontrolled, untreated brain metastasis. Participants with a history of treated and, at the time of screening, stable central nervous system (CNS) metastases are eligible, provided they meet all the following:

• Brain imaging at screening shows no evidence of interim progression, is clinically stable for ≥ 4 weeks, and has no evidence of new brain metastases
• Have measurable disease and/or evaluable disease outside CNS
• No ongoing requirement for corticosteroids as therapy for CNS disease; off corticosteroids ≥ 14 days before dosing with study drug; anticonvulsants at a stable dose are allowed
• No stereotactic radiation or whole-brain radiation ≤ 14 days before the first dose of study drug
• History of interstitial lung disease (ILD), or ≥ Grade 2 noninfectious pneumonitis ≤ 2 years before the first dose of the study drug, or has current ILD/noninfectious pneumonitis, or where suspected active ILD/noninfectious pneumonitis cannot be ruled out by imaging during screening.
• Participants with active or chronic corneal disorder, including but not limited to Sjögren's, Fuch's corneal dystrophy, history of corneal transplantation, corneal keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration, other active ocular conditions and any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.

Note: Other protocol defined Inclusion/Exclusion 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

China · 7 centers

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• Chongqing University Cancer Hospital — Chongqing
• The First Affiliated Hospital of Xiamen University — Xiamen
• Henan Cancer Hospital — Zhengzhou
• Rui Jin Hospital Shanghai Jiao Tong University School of Medicinejiading Branch — Shanghai
• West China Hospital, Sichuan University — Chengdu
• Zhejiang Cancer Hospital — Hangzhou

Australia · 4 centers

• Blacktown Cancer and Haematology Centre — Blacktown
• Cancer Research South Australia — Adelaide
• Monash Health — Clayton
• The Alfred Hospital — Melbourne

United States · 3 centers

• The University of Texas Md Anderson Cancer Center — Houston
• Next Oncology — San Antonio
• Next Virginia — Fairfax

Identifiers

NCT: NCT07181681 · BG-C0902-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗