All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Tislelizumab

Immunoglobulins

Antineoplastic Agents, Immunological

BGB-C354 monotherapy doses at sequentially increasing levels.

Participants will enroll at safe dose levels recommended by the Safety Monitoring Committee (SMC) for further evaluation.

The dose expansion phase begins after determining the recommended dose for expansion (RDFE) and schedule from Phase 1a, exploring at least 2 dose levels for optimization.

BGB-C354 and tislelizumab will start at the RDFE-1 level set by the SMC using Phase 1a data, or at a dose level lower than the highest tolerable level established in Part A.

BGB-C354

Study Director

This is a first-in-human, Phase 1a/1b study to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BGB-C354 alone and in combination with tislelizumab in participants with advanced solid tumors.

Study details include:

* The study will be conducted in 2 phases: Phase 1a (Monotherapy Dose Escalation and Safety Expansion) and Phase 1b (Dose Expansion).
* The visit frequency will be approximately every 21 days during study treatment, and higher frequencies may be considered based on emerging data. The maximum treatment duration will be up to 2 years.
* The study duration is estimated to be approximately 5 years.

Phase 1 First-in-Human Study of BGB-C354 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors

A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of BGB-C354, an Antibody-Drug Conjugate Targeting B7H3, Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

Number of participants with AEs and SAEs characterized by type, frequency, severity (as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 \[NCI-CTCAE v 5.0\]), timing, seriousness, and relationship to study drug(s); physical examinations; electrocardiograms (ECGs); and laboratory assessments as needed; and adverse events meeting protocol-defined dose-limitingtoxicity (DLT) criteria

Defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% or the highest dose administered, respectively

The potential RDFE(s) of BGB-C354 will be determined based on the MTD or MAD, taking into consideration the long-term tolerability, pharmacokinetics (PK), preliminary antitumor activity, and any other relevant data, as available

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 Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

The RP2D of BGB-C354 will be determined based on safety, PK, pharmacodynamics, preliminary antitumor activity, and other relevant data, as available.

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.

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.

DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease as determined from tumor assessments by the investigator using RECIST v1.1.

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.determined from tumor assessments by the investigator using RECIST v1.1.

BeiGene

Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Diffuse Intrinsic Pontine Glioma

Brain Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Stem Neoplasms

Infratentorial Neoplasms

Neuroepithelioma

Patients with DIPG for whom CAR T cells will be delivered into the ventricular system

Interventions:

Biological: Autologous B7H3-specific chimeric antigen receptor (CAR) T cell with additional of IL-7Ra signaling domain Dose level: 1x10e7 CAR T cell, 3x10e7 CAR T cell, 10x10e7 CAR T cell

Autologous T cells lentivirally transduced to express a B7H3 specific chimeric antigen receptor (CAR) with additional of IL-7 receptor alpha signalingdomain given via indwelling central nervous system (CNS) catheter

B7H3 specific CAR T cell with IL-7Ra signaling domain

Piti Techavichit Associate Professor, MD

Koramit Suppipat, MD

Kanhatai Chiengthong, MD

Supannikar Tawinwung, PhD

A Phase 1 clinical trial to evaluate the safety and early efficacy of CAR T-cell with IL-7Ra signal targeting B7H3 in children with diffuse intrinsic pontine glioma (DIPG) patients after complete standard treatments.

The brain tumor known as Diffuse Intrinsic Pontine Glioma is commonly found in children aged between 5 to 10 years. This type of tumor is aggressive and infiltrates the structures of the brain stem. Treatment options are limited due to the location of the tumor, making it impossible to surgically remove the mass like other brain cancers. The standard treatment for this type of tumor is radiation therapy, as this type of cancer does not respond to chemotherapy or currently available targeted drugs. However, radiation therapy has been found to be ineffective and does not improve survival rates.

Currently, there is development in cancer treatment using immunotherapy, where the patient's immune cells are genetically modified to target the cancer, also known as CAR T cells, for the treatment of recurrent or refractory cancers in solid tumors and brain cancers. The research project aims to study the efficacy and safety of treating patients with pontine glioma using T cells that are antigen-specific and have signals from the interleukin-7 receptor alpha and are specific to the B7H3 antigen on the tumor surface. This research is the first of its kind in Thai patients. The research project expects that this treatment will be highly safe and effective in controlling diffuse pontine glioma.

Safety and Efficacy of Loco-regional B7H3 IL-7Ra CAR T Cell in DIPG

Safety and Efficacy of Intraventricular Infusion of B7H3 With IL-7 Receptor Alpha Signaling Chimeric Antigen Receptor T Cell in Diffuse Intrinsic Pontine Glioma

The persistence and distribution of B7H3-IL7Ra CAR T cells in the CSF and peripheral blood of diffuse intrinsic pontine glioma patients will be measured by flow cytometry.

Serum cytokine level measurement before and after B7-H3-IL7Ra CAR T-cell infusion.

The incidence of adverse events assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0

The overall response rate will be assessed using radiologic response criteria that use the standard sum of the two longest 2D perpendicular diameters to distinguish stable disease, progressive disease (\>25% increase), partial response (\>50% decrease), and complete response (no evaluable or measurable disease).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 1 First-in-Human Study of BGB-C354 Alone and in Combination With Tislelizumab in Participants With Advanced Solid Tumors	NCT06422520	Advanced Solid ...	BGB-C354 Tislelizumab	18 Years -	BeiGene
Safety and Efficacy of Loco-regional B7H3 IL-7Ra CAR T Cell in DIPG	NCT06221553	DIPG Brain Tumo... Diffuse Intrins...	B7H3 specific C...	1 Year - 18 Years	Chulalongkorn University

Spots Global Cancer Trial Database for b7h3

Every month we try and update this database with for b7h3 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for b7h3

Every month we try and update this database with for b7h3 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for b7h3 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.