First-Time-in-Human Study of GSK4381562 in Participants With Advanced Solid Tumors

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Dostarlimab; Drug: Belrestotug; Drug: Nelistotug; Drug: GSK5764227; Drug: Remzistotug

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • GSK Investigational Site
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
• China
  • Chengdu, China, 610041
    • GSK Investigational Site
  • Jinan, China, 250117
    • GSK Investigational Site
  • Shanghai, China, 200126
    • GSK Investigational Site
  • Wuhan, China, 430022
    • GSK Investigational Site
• France
  • Dijon, France, 21000
    • GSK Investigational Site
  • Lille, France, 59000
    • GSK Investigational Site
• Japan
  • Chiba, Japan, 277-8577
    • GSK Investigational Site
  • Tokyo, Japan, 104-0045
    • GSK Investigational Site
• South Korea
  • Seoul, South Korea, 03080
    • GSK Investigational Site
  • Seoul, South Korea, 03722
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Madrid, Spain, 28040
    • GSK Investigational Site
  • Madrid, Spain, 28050
    • GSK Investigational Site
  • Málaga, Spain, 29010
    • GSK Investigational Site
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • GSK Investigational Site
  • Sutton, United Kingdom, SM2 5PT
    • GSK Investigational Site
• United States
  • California
    • San Francisco, California, United States, 94158
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• 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 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• 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.

Exclusion Criteria:

• 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 1. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: China Cohort: Participants receiving dostarlimab (Arm G)	Drug: Dostarlimab; Dostarlimab will be administered.
Experimental: Participants Receiving remzistotug Monotherapy (Arm A)	Drug: Remzistotug; Remzistotug will be administered.
Experimental: Participants Receiving remzistotug Plus Dostarlimab (Arm B)	Drug: Dostarlimab; Dostarlimab will be administered.; Drug: Remzistotug; Remzistotug will be administered.
Experimental: Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)	Drug: Dostarlimab; Dostarlimab will be administered.; Drug: Belrestotug; Belrestotug will be administered.; Drug: Remzistotug; Remzistotug will be administered.
Experimental: Participants Receiving Dostarlimab Plus belrestotug (Arm D)	Drug: Dostarlimab; Dostarlimab will be administered.; Drug: Belrestotug; Belrestotug will be administered.
Experimental: Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)	Drug: Dostarlimab; Dostarlimab will be administered.; Drug: Belrestotug; Belrestotug will be administered.; Drug: Remzistotug; Remzistotug will be administered.
Experimental: Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)	Drug: Dostarlimab; Dostarlimab will be administered.; Drug: Belrestotug; Belrestotug will be administered.; Drug: Nelistotug; Nelistotug will be administered.
Experimental: Participants Receiving GSK5764227 Plus dostarlimab (Arm I)	Drug: Dostarlimab; Dostarlimab will be administered.; Drug: GSK5764227; GSK5764227 will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Arms A, B, C, I: Number of Participants with dose-limiting toxicities (DLTs)	Up to 21 days
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to 27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Withdrawals due to AEs	Number of participants with adverse events leading to permanent discontinuation of study treatment or withdrawal from study by overall frequency will be assessed.	Up to 27 months
Number of Participants With Positive ADA to Dostarlimab		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 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
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
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		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
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
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
Overall Response Rate (ORR)	Objective response rate will be calculated as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. It is defined as the percentage of participants with a best overall confirmed complete response (CR) or partial response (PR) at any time as per disease-specific criteria.	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
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
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
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 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
Cmax of dostarlimab in combination with remzistotug and belrestotug		Up to 27 months
Cmax of dostarlimab in combination with belrestotug and remzistotug		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
Cmin of dostarlimab in combination with remzistotug and belrestotug		Up to 27 months
Cmin of dostarlimab in combination with belrestotug and remzistotug		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 and remzistotug		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 remzistotug and belrestotug		Up to 27 months
AUC(0-infinity) of dostarlimab in combination with belrestotug and remzistotug		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 and remzistotug		Up to 27 months
Cmin of belrestotug in combination with dostarlimab and belrestotug		Up to 27 months
Cmin of belrestotug in combination with dostarlimab and remzistotug		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 and remzistotug		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 and remzistotug		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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2022
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 14, 2022

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: fallopian tube; Head and neck squamous cell carcinoma (HNSCC); Metastatic solid tumor; Advanced solid tumors; Colorectal cancer (CRC); Non-small-cell lung cancer (NSCLC); Dostarlimab; GSK4428859A; Anticancer agents; Breast cancer (BC); Clear cell renal cell cancer (ccRCC); Gastric cancer (GC); Endometrial cancer (EC); Epithelial ovarian; Belrestotug; Nelistotug; GSK5764227; Remzistotug; and primary peritoneal cancers
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Neoplastic Processes; Lung Neoplasms; Genital Neoplasms, Female; Skin Diseases; Breast Diseases; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Squamous Cell Carcinoma of Head and Neck; Neoplasms; Stomach Neoplasms; Colorectal Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Endometrial Neoplasms; Antineoplastic Agents; dostarlimab
• Other Study ID Numbers: 217228; 2023-509414-11-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No