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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 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)
研究概览
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
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)
- •gastric cancer (GC)
- •colorectal cancer (CRC)
- •endometrial cancer (EC)
- •epithelial ovarian, fallopian tube, and primary peritoneal cancers- Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists.
- •Measurable disease per RECIST 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
- •Life expectancy of at least 12 weeks.
- •Adequate organ function, as defined in the protocol.
- •For participants enrolled in a PK/PD cohort, participant agrees to a fresh tumor biopsy during Screening and at approximately 6-weeks after treatment initiation.
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
- •Non clinically relevant Grade 2 toxicities, not constituting a safety risk by investigator judgment are allowed.
- •Participant has a known additional malignancy that progressed or required active treatment within the last 2 years.
研究组 & 干预措施
Participants Receiving remzistotug Monotherapy (Arm A)
Experimental
干预措施: Remzistotug (Drug)
Participants Receiving remzistotug Plus Dostarlimab (Arm B)
Experimental
干预措施: Remzistotug (Drug)
Participants Receiving remzistotug Plus Dostarlimab (Arm B)
Experimental
干预措施: Dostarlimab (Drug)
Participants Receiving Dostarlimab Plus belrestotug (Arm D)
Experimental
干预措施: Dostarlimab (Drug)
China Cohort: Participants receiving dostarlimab (Arm G)
Experimental
干预措施: Dostarlimab (Drug)
Participants Receiving GSK5764227 Plus dostarlimab (Arm I)
Experimental
干预措施: Dostarlimab (Drug)
Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)
Experimental
干预措施: Nelistotug (Drug)
Participants Receiving Dostarlimab Plus belrestotug (Arm D)
Experimental
干预措施: Belrestotug (Drug)
Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)
Experimental
干预措施: Belrestotug (Drug)
Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)
Experimental
干预措施: Dostarlimab (Drug)
Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)
Experimental
干预措施: Remzistotug (Drug)
Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)
Experimental
干预措施: Remzistotug (Drug)
Participants Receiving GSK5764227 Plus dostarlimab (Arm I)
Experimental
干预措施: GSK5764227 (Drug)
Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)
Experimental
干预措施: Dostarlimab (Drug)
Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)
Experimental
干预措施: Belrestotug (Drug)
Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)
Experimental
干预措施: Dostarlimab (Drug)
Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)
Experimental
干预措施: Belrestotug (Drug)
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
- 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)
- Number of Participants With Clinically Significant Changes in Laboratory Parameters, Electrocardiogram (ECG) and Vital Signs(Up to 24 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 Positive ADA to nelistotug(Up to 27 months)
- Cmax following administration of dostarlimab with belrestotug(Up to 27 months)
- Cmin following administration of dostarlimab with belrestotug(Up to 27 months)
- AUC(0-t) 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 belrestotug(Up to 27 months)
- Cmax of dostarlimab in combination with belrestotug and nelistotug(Up to 27 months)
- Cmin of dostarlimab in combination with belrestotug(Up to 27 months)
- Cmin of dostarlimab in combination with belrestotug and nelistotug(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 nelistotug(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 belrestotug(Up to 27 months)
- AUC(0-infinity) of dostarlimab in combination with belrestotug and nelistotug(Up to 27 months)
- Cmax of belrestotug in combination with dostarlimab and nelistotug(Up to 27 months)
- Cmin of belrestotug in combination with dostarlimab(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(Up to 27 months)
- AUC (0-t) of belrestotug in combination with dostarlimab and nelistotug(Up to 27 months)
- Number of Participants With Dose Reductions or Delays(Up to 24 months)
- Number of Participants With Withdrawals due to AEs(Up to 27 months)
- Overall Response Rate (ORR)(Up to 24 months)
- Number of Participants With Positive ADA to Dostarlimab(Up to 27 months)
- Titers of ADA to Dostarlimab(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 nelistotug(Up to 27 months)
- 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)
研究者
研究点 (27)
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