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

NCT ID: NCT05277051

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

158 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-22

Study Completion Date

2027-08-31

Brief Summary

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This is a first time in-human (FTIH) study designed to investigate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of GSK4381562 in participants with select loco-regionally recurrent solid tumors or metastatic solid tumors where curative or standard treatment options have been exhausted.

Detailed Description

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Conditions

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Neoplasms

Keywords

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Advanced solid tumors Metastatic solid tumor Anticancer agents Dostarlimab GSK4381562 GSK4428859A Belrestotug Nelistotug GSK5764227 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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

4 Dose Escalation arms (Arm A: GSK4381562 alone; Arm B: GSK4381562 plus dostarlimab; Arm C: GSK4381562 plus dostarlimab plus belrestotug; Arm I: GSK5764227 plus dostarlimab) and 5 other arms (Arm D: dostarlimab plus belrestotug; Arm E: dostarlimab plus belrestotug plus GSK4381562; Arm F: dostarlimab plus belrestotug plus nelistotug; Arm G: China cohort: dostarlimab; Arm H: China cohort: dostarlimab plus belrestotug).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Participants receiving GSK4381562 monotherapy (Arm A)

Group Type EXPERIMENTAL

GSK4381562

Intervention Type DRUG

GSK4381562 will be administered.

Participants receiving GSK4381562 plus dostarlimab (Arm B)

Group Type EXPERIMENTAL

GSK4381562

Intervention Type DRUG

GSK4381562 will be administered.

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

Participants receiving GSK4381562 plus dostarlimab plus belrestotug (Arm C)

Group Type EXPERIMENTAL

GSK4381562

Intervention Type DRUG

GSK4381562 will be administered.

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

Belrestotug

Intervention Type DRUG

Belrestotug will be administered.

Participants receiving dostarlimab plus belrestotug (Arm D)

Group Type EXPERIMENTAL

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

Belrestotug

Intervention Type DRUG

Belrestotug will be administered.

Participants receiving dostarlimab plus belrestotug plus GSK4381562 (Arm E)

Group Type EXPERIMENTAL

GSK4381562

Intervention Type DRUG

GSK4381562 will be administered.

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

Belrestotug

Intervention Type DRUG

Belrestotug will be administered.

Participants receiving dostarlimab plus belrestotug plus nelistotug (Arm F)

Group Type EXPERIMENTAL

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

Belrestotug

Intervention Type DRUG

Belrestotug will be administered.

Nelistotug

Intervention Type DRUG

Nelistotug will be administered.

China Cohort: Participants receiving dostarlimab (Arm G)

Group Type EXPERIMENTAL

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

China Cohort: Participants receiving dostarlimab plus belrestotug (Arm H)

Group Type EXPERIMENTAL

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

Belrestotug

Intervention Type DRUG

Belrestotug will be administered.

Participants receiving GSK5764227 plus dostarlimab (Arm I)

Group Type EXPERIMENTAL

Dostarlimab

Intervention Type DRUG

Dostarlimab will be administered.

GSK5764227

Intervention Type DRUG

GSK5764227 will be administered.

Interventions

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GSK4381562

GSK4381562 will be administered.

Intervention Type DRUG

Dostarlimab

Dostarlimab will be administered.

Intervention Type DRUG

Belrestotug

Belrestotug will be administered.

Intervention Type DRUG

Nelistotug

Nelistotug will be administered.

Intervention Type DRUG

GSK5764227

GSK5764227 will be administered.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

San Francisco, California, United States

Site Status RECRUITING

GSK Investigational Site

Charlotte, North Carolina, United States

Site Status RECRUITING

GSK Investigational Site

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

GSK Investigational Site

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

GSK Investigational Site

Dallas, Texas, United States

Site Status RECRUITING

GSK Investigational Site

San Antonio, Texas, United States

Site Status RECRUITING

GSK Investigational Site

Salt Lake City, Utah, United States

Site Status RECRUITING

GSK Investigational Site

Nedlands, Western Australia, Australia

Site Status RECRUITING

GSK Investigational Site

Ottawa, Ontario, Canada

Site Status RECRUITING

GSK Investigational Site

Toronto, Ontario, Canada

Site Status RECRUITING

GSK Investigational Site

Chengdu, , China

Site Status RECRUITING

GSK Investigational Site

Jinan, , China

Site Status RECRUITING

GSK Investigational Site

Shanghai, , China

Site Status RECRUITING

GSK Investigational Site

Wuhan, , China

Site Status RECRUITING

GSK Investigational Site

Dijon, , France

Site Status COMPLETED

GSK Investigational Site

Lille, , France

Site Status COMPLETED

GSK Investigational Site

Chiba, , Japan

Site Status RECRUITING

GSK Investigational Site

Tokyo, , Japan

Site Status RECRUITING

GSK Investigational Site

Seoul, , South Korea

Site Status COMPLETED

GSK Investigational Site

Seoul, , South Korea

Site Status COMPLETED

GSK Investigational Site

Barcelona, , Spain

Site Status RECRUITING

GSK Investigational Site

Madrid, , Spain

Site Status COMPLETED

GSK Investigational Site

Madrid, , Spain

Site Status COMPLETED

GSK Investigational Site

Málaga, , Spain

Site Status RECRUITING

GSK Investigational Site

Manchester, , United Kingdom

Site Status COMPLETED

GSK Investigational Site

Sutton, , United Kingdom

Site Status COMPLETED

Countries

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United States Australia Canada China France Japan South Korea Spain United Kingdom

Central Contacts

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US GSK Clinical Trials Call Center

Role: CONTACT

Phone: 877-379-3718

Email: [email protected]

EU GSK Clinical Trials Call Center

Role: CONTACT

Phone: +44 (0) 20 89904466

Email: [email protected]

Facility Contacts

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US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

US GSK Clinical Trials Call Center

Role: primary

EU GSK Clinical Trials Call Centre

Role: backup

Other Identifiers

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2023-509414-11

Identifier Type: OTHER

Identifier Source: secondary_id

217228

Identifier Type: -

Identifier Source: org_study_id