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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05277051
• Other study ID #: 217228
• Secondary ID: 2021-004968-95
• Status: Recruiting
• Phase: Phase 1
• Start date: March 22, 2022
• Est. completion date: October 14, 2026

Study information

• Verified date: January 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: October 14, 2026
• Est. primary completion date: October 14, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.
• 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)
• ovarian epithelial cancer (OEC)
• 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 GSK4381562):

• 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.
• 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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• GSK4381562
GSK4381562 will be administered.
• Dostarlimab
Dostarlimab will be administered.
• GSK4428859A
GSK4428859A will be administered.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Nedlands	Western Australia
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
China	GSK Investigational Site	Shnghai
France	GSK Investigational Site	Dijon
France	GSK Investigational Site	Lille
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Málaga
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Sutton
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Japan,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Arms A, B, C: Number of participants with dose-limiting toxicities (DLTs)		Up to 21 days
Primary	Arms A, B, C, D: Number of participants with adverse events (AEs) and serious adverse events (SAEs)		Up to 27 months
Secondary	Number of participants with clinically significant changes in laboratory parameters, electrocardiogram (ECG) and vital signs		Up to 24 months
Secondary	Number of participants with dose reductions or delays		Up to 24 months
Secondary	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
Secondary	Overall response rate (ORR)	Overall 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
Secondary	Number of participants with positive antidrug antibodies (ADA) to GSK4381562		Up to 27 months
Secondary	Titers of ADA to GSK4381562		Up to 27 months
Secondary	Number of participants with positive ADA to dostarlimab		Up to 27 months
Secondary	Titers of ADA to dostarlimab		Up to 27 months
Secondary	Number of participants with positive ADA to GSK4428859A		Up to 27 months
Secondary	Titers of ADA to GSK4428859A		Up to 27 months
Secondary	Serum concentrations of GSK4381562		Up to 4 months
Secondary	Serum concentrations of dostarlimab		Up to 4 months
Secondary	Serum Concentrations of GSK4428859A		Up to 4 months
Secondary	Maximum observed plasma concentration (Cmax) of GSK4381562 monotherapy		Up to 27 months
Secondary	Cmax of GSK4381562 in combination with dostarlimab		Up to 27 months
Secondary	Cmax of GSK4381562 in combination with GSK4428859A		Up to 27 months
Secondary	Cmax following administration of dostarlimab in combination with GSK4428859A		Up to 27 months
Secondary	Minimum observed plasma concentration (Cmin) of GSK4381562 monotherapy		Up to 27 months
Secondary	Cmin of GSK4381562 in combination with dostarlimab		Up to 27 months
Secondary	Cmin of GSK4381562 in combination with GSK4428859A		Up to 27 months
Secondary	Cmin following administration of dostarlimab in combination with GSK4428859A		Up to 27 months
Secondary	Area under the plasma concentration curve from time zero to last time of quantifiable concentration (AUC[0-t]) of GSK4381562		Up to 27 months
Secondary	AUC(0-t) of GSK4381562 in combination with dostarlimab		Up to 27 months
Secondary	AUC(0-t) of GSK4381562 in combination with GSK4428859A		Up to 27 months
Secondary	AUC(0-t) following administration of dostarlimab in combination with GSK4428859A		Up to 27 months
Secondary	AUC from time zero to infinity (AUC[0-infinity]) of single dosing of GSK4381562		Up to 27 months
Secondary	AUC(0-infinity) of single dosing of GSK4381562 in combination with dostarlimab		Up to 27 months
Secondary	AUC(0-infinity) of single dosing of GSK4381562 in combination with GSK4428859A		Up to 27 months
Secondary	AUC(0-infinity) following administration of dostarlimab in combination with GSK4428859A		Up to 27 months