临床试验/NCT05277051

NCT05277051

进行中（未招募）

1 期

A Phase 1 First-Time-in-Human, Open-Label Study of GSK4381562 Administered as Monotherapy and in Combination With Anticancer Agents in Participants With Selected Advanced Solid Tumors

GlaxoSmithKline27 个研究点分布在 9 个国家目标入组 152 人2022年3月22日

适应症Neoplasms

干预措施Remzistotug Dostarlimab Belrestotug Nelistotug GSK5764227

概览

阶段: 1 期
干预措施: Remzistotug
疾病 / 适应症: Neoplasms
发起方: GlaxoSmithKline
入组人数: 152
试验地点: 27
主要终点: Arms A, B, C, I: Number of Participants with dose-limiting toxicities (DLTs)
状态: 进行中（未招募）
最后更新: 上个月

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This is a first time in-human (FTIH) study designed to investigate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of remzistotug in participants with select loco-regionally recurrent solid tumors or metastatic solid tumors where curative or standard treatment options have been exhausted.

注册库

clinicaltrials.gov

开始日期

2022年3月22日

结束日期

2027年8月31日

最后更新

上个月

研究类型

Interventional

研究设计

Sequential

性别

All

研究者

发起方

GlaxoSmithKline

责任方

Sponsor

入排标准

入选标准

•A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
•Is not a woman of childbearing potential (WOCBP) or
•Is a WOCBP and using a contraceptive method that is highly effective with a failure rate of less than (\<)1 percent (\[%\] per year), during the intervention period and for specified time after end of study treatment.
•A WOCBP must have a negative highly sensitive pregnancy test within 24-48 hours before the first dose of study intervention.
•Requirement for Arm I only: Male participants agree to use contraception and for their female partner to use contraception, if applicable.
•Histological or cytological documentation of loco-regionally recurrent solid tumors where curative treatment options have been exhausted, or metastatic solid tumors; types as follows:
•head and neck squamous cell carcinoma (HNSCC)
•non-small-cell lung cancer (NSCLC)
•breast cancer (BC)
•clear cell renal cell cancer (ccRCC)

排除标准

•Prior treatment with the following therapies (specified time periods are from last dose of prior treatment to first dose of study intervention):
•Any therapy directed against Polio virus receptor (PVR)-related immunoglobulin domain-containing (PVRIG) (COM701 or other anti-PVRIG monoclonal antibody \[mAb\]) or other cluster of differentiation (CD)226 axis receptor (T-cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain \[TIGIT\] or CD96) at any time.
•For Arm I only, prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents.
•Other prior immunotherapy, chemotherapy, targeted therapy, biological therapy or radiation therapy within specified periods as defined in the protocol.
•Investigational therapy: if the participant has participated in a clinical study and has received an investigational product within 4 weeks or 5 half-lives of the investigational product (whichever is shorter).
•Prior allogenic or autologous bone marrow transplantation or other solid organ transplantation.
•Toxicity from previous anticancer treatment, including:
•Greater than or equal to Grade 3 immune-mediated toxicity considered related to prior immunotherapy and that led to treatment discontinuation; or
•History of myocarditis of any grade during a previous treatment with immunotherapy
•Toxicity related to prior treatment that has not resolved to less than or equal to (\<=) Grade

研究组 & 干预措施

Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)

干预措施: Remzistotug

Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)

干预措施: Dostarlimab

Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)

干预措施: Belrestotug

Participants Receiving remzistotug Monotherapy (Arm A)

干预措施: Remzistotug

Participants Receiving remzistotug Plus Dostarlimab (Arm B)

干预措施: Remzistotug

Participants Receiving remzistotug Plus Dostarlimab (Arm B)

干预措施: Dostarlimab

Participants Receiving Dostarlimab Plus belrestotug (Arm D)

干预措施: Dostarlimab

Participants Receiving Dostarlimab Plus belrestotug (Arm D)

干预措施: Belrestotug

Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)

干预措施: Remzistotug

Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)

干预措施: Dostarlimab

Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)

干预措施: Belrestotug

Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)

干预措施: Dostarlimab

Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)

干预措施: Belrestotug

Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)

干预措施: Nelistotug

China Cohort: Participants receiving dostarlimab (Arm G)

干预措施: Dostarlimab

Participants Receiving GSK5764227 Plus dostarlimab (Arm I)

干预措施: Dostarlimab

Participants Receiving GSK5764227 Plus dostarlimab (Arm I)

干预措施: GSK5764227

结局指标

主要结局

Arms A, B, C, I: Number of Participants with dose-limiting toxicities (DLTs)

时间窗: Up to 21 days

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

时间窗: Up to 27 months

次要结局

Cmin of belrestotug in combination with dostarlimab and belrestotug(Up to 27 months)
Cmin of belrestotug in combination with dostarlimab(Up to 27 months)
Number of Participants With Positive ADA to nelistotug(Up to 27 months)
Titers of ADA to nelistotug(Up to 27 months)
Number of Participants With Positive ADA to GSK5764227(Up to 27 months)
Titers of ADA to GSK5764227(Up to 27 months)
Cmin of belrestotug in combination with dostarlimab and remzistotug(Up to 27 months)
Titers of ADA to Dostarlimab(Up to 27 months)
Number of Participants With Positive ADA to belrestotug(Up to 27 months)
Titers of ADA to belrestotug(Up to 27 months)
Number of Participants With Withdrawals due to AEs(Up to 27 months)
Number of Participants With Clinically Significant Changes in Laboratory Parameters, Electrocardiogram (ECG) and Vital Signs(Up to 24 months)
Number of Participants With Dose Reductions or Delays(Up to 24 months)
Number of Participants With Positive ADA to Dostarlimab(Up to 27 months)
Overall Response Rate (ORR)(Up to 24 months)
Number of Participants With Positive Antidrug Antibodies (ADA) to remzistotug(Up to 27 months)
Titres of ADA to remzistotug(Up to 27 months)
Serum Concentrations of remzistotug(Up to 4 months)
Serum Concentrations of dostarlimab(Up to 4 months)
Serum Concentrations of belrestotug(Up to 4 months)
Serum Concentrations of nelistotug(Up to 4 months)
Serum Concentrations of GSK5764227(Up to 4 months)
Maximum Observed Plasma Concentration (Cmax) of remzistotug Monotherapy(Up to 27 months)
Cmax of remzistotug in Combination With Dostarlimab(Up to 27 months)
Cmax of remzistotug in Combination With dostarlimab and belrestotug(Up to 27 months)
Cmax following administration of dostarlimab with belrestotug(Up to 27 months)
Minimum Observed Plasma Concentration (Cmin) of remzistotug Monotherapy(Up to 27 months)
Cmin of remzistotug in Combination With Dostarlimab(Up to 27 months)
Cmin of remzistotug in Combination With dostarlimab and belrestotug(Up to 27 months)
Cmin following administration of dostarlimab with belrestotug(Up to 27 months)
Cmax of dostarlimab in combination with GSK5764227(Up to 27 months)
Cmax of dostarlimab in combination with remzistotug and belrestotug(Up to 27 months)
Cmax of dostarlimab in combination with belrestotug(Up to 27 months)
Cmax of dostarlimab in combination with belrestotug and remzistotug(Up to 27 months)
Cmax of dostarlimab in combination with belrestotug and nelistotug(Up to 27 months)
China cohort: Cmax of dostarlimab monotherapy(Up to 18 months)
Cmin of dostarlimab in Combination With remzistotug(Up to 27 months)
Cmin of dostarlimab in combination with GSK5764227(Up to 18 months)
Cmax of belrestotug in combination with dostarlimab and nelistotug(Up to 27 months)
Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of remzistotug(Up to 27 months)
AUC(0-t) of remzistotug in Combination With Dostarlimab(Up to 27 months)
AUC(0-t) of remzistotug in Combination With dostarlimab and belrestotug(Up to 27 months)
AUC(0-t) following administration of dostarlimab with belrestotug(Up to 27 months)
AUC From Time Zero to Infinity (AUC[0-infinity]) of Single Dosing of remzistotug(Up to 27 months)
AUC(0-infinity) of Single Dosing of remzistotug in Combination with Dostarlimab(Up to 27 months)
AUC(0-infinity) of Single Dosing of remzistotug in Combination With dostarlimab and belrestotug(Up to 27 months)
AUC(0-infinity) of Single Dosing of remzistotug following administration of dostarlimab with belrestotug(Up to 27 months)
Cmax of dostarlimab in Combination With remzistotug(Up to 27 months)
Cmin of dostarlimab in combination with remzistotug and belrestotug(Up to 27 months)
Cmin of dostarlimab in combination with belrestotug(Up to 27 months)
Cmin of dostarlimab in combination with belrestotug and remzistotug(Up to 27 months)
Cmin of dostarlimab in combination with belrestotug and nelistotug(Up to 27 months)
China cohort: Cmin of dostarlimab monotherapy(Up to 18 months)
AUC(0-t) of dostarlimab in Combination With remzistotug(Up to 27 months)
AUC(0-t) of dostarlimab in combination with GSK5764227(Up to 18 months)
AUC(0-t) of dostarlimab in combination with remzistotug and belrestotug(Up to 27 months)
AUC(0-t) of dostarlimab in combination with belrestotug(Up to 27 months)
AUC(0-t) of dostarlimab in combination with belrestotug and remzistotug(Up to 27 months)
AUC(0-t) of dostarlimab in combination with belrestotug and nelistotug(Up to 27 months)
China cohort: AUC(0-t) of dostarlimab monotherapy(Up to 18 months)
AUC(0-infinity) of dostarlimab in Combination With remzistotug(Up to 27 months)
AUC(0-infinity) of dostarlimab in combination with GSK5764227(Up to 27 months)
AUC(0-infinity) of dostarlimab in combination with remzistotug and belrestotug(Up to 27 months)
AUC(0-infinity) of dostarlimab in combination with belrestotug(Up to 27 months)
AUC(0-infinity) of dostarlimab in combination with belrestotug and remzistotug(Up to 27 months)
AUC(0-infinity) of dostarlimab in combination with belrestotug and nelistotug(Up to 27 months)
China cohort: AUC(0-infinity) of dostarlimab monotherapy(Up to 18 months)
T1/2 of dostarlimab in Combination With remzistotug(Up to 27 months)
T1/2 of dostarlimab in combination with GSK5764227(Up to 18 months)
China cohort: T1/2 of dostarlimab monotherapy(Up to 18 months)
Cmax of belrestotug in combination with dostarlimab and belrestotug(Up to 27 months)
Cmax of belrestotug in combination with dostarlimab(Up to 27 months)
Cmax of belrestotug in combination with dostarlimab and remzistotug(Up to 27 months)
Cmin of belrestotug in combination with dostarlimab and nelistotug(Up to 27 months)
AUC (0-t) of belrestotug in combination with dostarlimab and belrestotug(Up to 27 months)
AUC (0-t) of belrestotug in combination with dostarlimab(Up to 27 months)
AUC (0-t) of belrestotug in combination with dostarlimab and remzistotug(Up to 27 months)
AUC (0-t) of belrestotug in combination with dostarlimab and nelistotug(Up to 27 months)
AUC (0-infinity) of belrestotug in combination with dostarlimab and belrestotug(Up to 27 months)
AUC (0- infinity) of belrestotug in combination with dostarlimab(Up to 27 months)
AUC (0- infinity) of belrestotug in combination with dostarlimab and remzistotug(Up to 27 months)
AUC (0- infinity) of belrestotug in combination with dostarlimab and nelistotug(Up to 27 months)
Cmax of nelistotug in combination with dostarlimab and belrestotug(Up to 27 months)
Cmin of nelistotug in combination with dostarlimab and belrestotug(Up to 27 months)
AUC (0-t) of nelistotug in combination with dostarlimab and belrestotug(Up to 27 months)
AUC (0-infinity) of nelistotug in combination with dostarlimab and belrestotug(Up to 27 months)
Cmax of GSK5764227 in combination with dostarlimab(Up to 18 months)
Cmin of GSK5764227 in combination with dostarlimab(Up to 18 months)
AUC (0-t) of GSK5764227 conjugated Ab in combination with dostarlimab(Up to 18 months)
AUC (0-t) of GSK5764227 small molecule toxin in combination with dostarlimab(Up to 18 months)
AUC (0-infinity) of GSK5764227 conjugated Ab in combination with dostarlimab(Up to 18 months)
AUC (0-infinity) of GSK5764227 small molecule toxin in combination with dostarlimab(Up to 18 months)