Clinical trial NCT06803680: A Study of BGB-B455 in Adults With Advanced or Metastatic Solid Tumors
Official title: A Phase 1, Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B455 in Patients With Selected Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Keywords: Claudin-6
CLDN6+
advanced or metastatic solid tumor
CD3
BsAb
bispecific antibody
CD3-BsAb
CLDN
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2025-01-31
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if BGB-B455 can treat advanced or metastatic solid tumors expressing claudin 6 (CLDN6), a protein that is found on some tumors.

The main questions it aims to answer are:

* What is the recommended dosing for BGB-B455?
* What medical problems do participants have when taking BGB-B455?

The study has two parts:

* Phase 1a: dose escalation and safety expansion
* Phase 1b: dose expansion

Detailed description: Claudin proteins are cell proteins that can play an important role in how cancer starts and progresses. Because of its preferential expression in tumors compared to normal tissues, CLDN6 is an ideal tumor antigen to target for treatment. BGB-B455 is a bispecific antibody (BsAbs) that targets CLDN6 on tumor cells and the CD3 receptor on T cells, which may provide a CLDN6-dependent antitumor immune response in a more tolerable manner without undue systemic toxicity.

This new study will check how safe and helpful this potential anticancer drug is. In addition, this study will explore the recommended dosing level for BGB-B455. This drug will be tested by itself in participants with solid tumors expressing the CLDN6 protein.

This study is an open label study, meaning that both you and your study doctor will know what study drug/treatment you are given. This study has two parts:

* Phase 1a consists of a dose escalation part where increasing amounts of the study treatment are given to different dose cohorts, and a safety expansion part that will enroll additional participants at selected doses for further assessments.
* Phase 1b (dose expansion) will enroll participants at the best dose found in Phase 1a to see if it helps people with certain solid tumors.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed advanced or metastatic, and unresectable solid tumors who have previously received standard systemic therapy for advanced or metastatic disease or for whom treatment is not available or not tolerated.
* Agreement for collection of formalin-fixed paraffin-embedded (FFPE) tumor tissue for central CLDN6 testing and other biomarker assessments.
* Tumor CLDN6 expression (CDLN6+) by central immunohistochemistry testing is required for Phase 1a dose escalation Cohort 5 and higher.
* ≥ 1 measurable lesion as assessed by RECIST v1.1.
* Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
* Adequate organ function.

Exclusion Criteria:

* Prior systemic anticancer therapy, including chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin), targeted therapy, and antibody drug conjugates (ADCs) that are standard or investigational agents (including herbal medicine or Chinese \[or other country\] patent medicines, ≤ 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug(s).
* Palliative radiation treatment or other locoregional therapies ≤ 14 days before the first dose of study drug(s).
* Live vaccine ≤ 28 days before the first dose of study drug(s). Vaccines for COVID-19 are allowed except for any live vaccine that may become available. Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
* Any major surgical procedure ≤ 28 days before the first dose of study drug(s).
* History of prior ≥ Grade 3 cytokine release syndrome (CRS).
* Participants with toxicities (because of prior anticancer therapy) that have not recovered to baseline or stabilized, except for adverse events not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Phase 1a: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From the first dose of study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 7 months
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B455
timeFrame: Approximately 1 month
measure: Phase 1a: RDFE of BGB-B455
timeFrame: Approximately 1 month
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Approximately 18 months
Secondary outcomes:
measure: Phase 1a: ORR
timeFrame: Approximately 18 months
measure: Phase 1a and 1b: Duration of Response (DOR)
timeFrame: Approximately 18 months
measure: Phase 1a and 1b: Disease Control Rate (DCR)
timeFrame: Approximately 18 months
measure: Phase 1a and 1b: Time to Response (TTR)
timeFrame: Approximately 18 months
measure: Phase 1a and 1b: Serum concentrations of BGB-B455
timeFrame: Approximately 7 months
measure: Phase 1a and 1b: Number of participants with anti-drug antibodies (ADAs) to BGB-B455
timeFrame: Approximately 7 months
measure: Phase 1b: Progression-Free Survival (PFS)
timeFrame: Approximately 18 months
measure: Phase 1b: Number of participants with AEs
timeFrame: From the first dose of study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 7 months
measure: Phase 1a and 1b: Area under the concentration-time curve (AUC) of BGB-B455
timeFrame: Approximately 4 months
measure: Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-B455
timeFrame: Approximately 4 months
measure: Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-B455
timeFrame: Approximately 4 months
measure: Phase 1a and 1b: Trough Concentration (Ctrough) of BGB-B455
timeFrame: Approximately 7 months
measure: Phase 1a and 1b: Apparent clearance (CL) of BGB-B455
timeFrame: Approximately 4 months
measure: Phase 1a and 1b: Volume of distribution (Vd) of BGB-B455
timeFrame: Approximately 4 months
measure: Phase 1a and 1b: Accumulation Ratio of BGB-B455
timeFrame: Approximately 4 months
measure: Phase 1a and 1b: Terminal half-life (t1/2) of BGB-B455
timeFrame: Approximately 4 months
Other outcomes:
Locations:
city: Celebration
country: United States
facility: Adventhealth
state: Florida
city: Lake Mary
country: United States
facility: Florida Cancer Specialists and Research Institute
state: Florida
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institue
state: South Dakota
city: San Antonio
country: United States
facility: Ut Health San Antonio Mays Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Cancer Care Centre
state: Queensland
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Centerpudong
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: