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

NCT05277051 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2172282023-509414-11-00
• Study Type: interventional
• Target: 152
• Locations: 9 countries
• Sites: 26

Brief Summary

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.

Conditions

Neoplasms

Keywords

Advanced solid tumors; Metastatic solid tumor; Anticancer agents; Dostarlimab; Remzistotug; 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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (92)

• 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

  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

Study Arms (8)

Participants Receiving remzistotug Monotherapy (Arm A)

EXPERIMENTAL

Drug: Remzistotug

Participants Receiving remzistotug Plus Dostarlimab (Arm B)

EXPERIMENTAL

Drug: Remzistotug; Drug: Dostarlimab

Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)

EXPERIMENTAL

Drug: Remzistotug; Drug: Dostarlimab; Drug: Belrestotug

Participants Receiving Dostarlimab Plus belrestotug (Arm D)

EXPERIMENTAL

Drug: Dostarlimab; Drug: Belrestotug

Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)

EXPERIMENTAL

Drug: Remzistotug; Drug: Dostarlimab; Drug: Belrestotug

Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)

EXPERIMENTAL

Drug: Dostarlimab; Drug: Belrestotug; Drug: Nelistotug

China Cohort: Participants receiving dostarlimab (Arm G)

EXPERIMENTAL

Drug: Dostarlimab

Participants Receiving GSK5764227 Plus dostarlimab (Arm I)

EXPERIMENTAL

Drug: Dostarlimab; Drug: GSK5764227

Interventions

Remzistotug DRUG

Remzistotug will be administered.

Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E); Participants Receiving remzistotug Monotherapy (Arm A); Participants Receiving remzistotug Plus Dostarlimab (Arm B); Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)

Dostarlimab DRUG

Dostarlimab will be administered.

China Cohort: Participants receiving dostarlimab (Arm G); Participants Receiving Dostarlimab Plus belrestotug (Arm D); Participants Receiving GSK5764227 Plus dostarlimab (Arm I); Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F); Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E); Participants Receiving remzistotug Plus Dostarlimab (Arm B); Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)

Belrestotug DRUG

Belrestotug will be administered.

Participants Receiving Dostarlimab Plus belrestotug (Arm D); Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F); Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E); Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)

Nelistotug DRUG

Nelistotug will be administered.

Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)

GSK5764227 DRUG

GSK5764227 will be administered.

Participants Receiving GSK5764227 Plus dostarlimab (Arm I)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (26)

GSK Investigational Site

San Francisco, California, 94158, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28204, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84112, United States

Location

GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Chengdu, 610041, China

Location

GSK Investigational Site

Jinan, 250117, China

Location

GSK Investigational Site

Shanghai, 200126, China

Location

GSK Investigational Site

Wuhan, 430022, China

Location

GSK Investigational Site

Dijon, 21000, France

Location

GSK Investigational Site

Lille, 59000, France

Location

GSK Investigational Site

Chiba, 277-8577, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Seoul, 03080, South Korea

Location

GSK Investigational Site

Seoul, 03722, South Korea

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Manchester, M20 4BX, United Kingdom

Location

GSK Investigational Site

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Carcinoma, Renal Cell; Stomach Neoplasms; Colorectal Neoplasms; Endometrial Neoplasms

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Diseases, Female; Genital Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 4 Dose Escalation arms (Arm A: remzistotug alone; Arm B: remzistotug plus dostarlimab; Arm C: remzistotug plus dostarlimab plus belrestotug); Arm I: GSK5764227 plus dostarlimab) and 5 other arms, Arm D (dostarlimab plus belrestotug; Arm E (dostarlimab plus belrestotug plus remzistotug Arm F (dostarlimab plus belrestotug plus nelistotug; Arm G (China cohort: dostarlimab);

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 14, 2022
• Study Start: March 22, 2022
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

ES (4); US (7); KR (2); CA (2); CN (4); AU (1); JP (2); FR (2); GB (2)