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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05277051

Collaborator

(none)

126

Enrollment

Locations

Arms

59.2

Anticipated Duration (Months)

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: GSK4381562 Drug: Dostarlimab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

126 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

2 Dose Escalation arms (GSK4381562 alone and GSK4381562 plus dostarlimab); additional participants may be enrolled in both study arms in PK/Pharmacodynamic (PD) cohorts at putative recommended Phase 2 dose (RP2D) level and/or at previously cleared dose levels (up to 15 participants)2 Dose Escalation arms (GSK4381562 alone and GSK4381562 plus dostarlimab); additional participants may be enrolled in both study arms in PK/Pharmacodynamic (PD) cohorts at putative recommended Phase 2 dose (RP2D) level and/or at previously cleared dose levels (up to 15 participants)

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 22, 2022

Anticipated Primary Completion Date :

Oct 31, 2024

Anticipated Study Completion Date :

Feb 26, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants receiving GSK4381562 monotherapy	Drug: GSK4381562 GSK4381562 will be administered.
Experimental: Participants receiving GSK4381562 plus dostarlimab	Drug: GSK4381562 GSK4381562 will be administered. Drug: Dostarlimab Dostarlimab will be administered.

Arm

Intervention/Treatment

Experimental: Participants receiving GSK4381562 monotherapy

Drug: GSK4381562

GSK4381562 will be administered.

Experimental: Participants receiving GSK4381562 plus dostarlimab

Drug: GSK4381562

GSK4381562 will be administered.

Drug: Dostarlimab

Dostarlimab will be administered.

Outcome Measures

Primary Outcome Measures

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

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]
Number of participants with adverse events leading to permanent discontinuation of study treatment or withdrawal from study by overall frequency will be assessed.
Overall response rate (ORR) [Up to 24 months]
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.
Number of participants with positive antidrug antibodies (ADA) to GSK4381562 [Up to 27 months]
Titers of ADA to GSK4381562 [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]
Plasma concentrations of GSK4381562 [Up to 4 months]
Maximum observed plasma concentration (Cmax) of GSK4381562 monotherapy [Up to 27 months]
Cmax of GSK4381562 in combination with dostarlimab [Up to 27 months]
Minimum observed plasma concentration (Cmin) of GSK4381562 monotherapy [Up to 27 months]
Cmin of GSK4381562 in combination with dostarlimab [UP to 27 months]
Area under the plasma concentration curve from time zero to last time of quantifiable concentration (AUC[0-t]) of GSK4381562 [Up to 27 months]
AUC(0-t) of GSK4381562 in combination with dostarlimab [Up to 27 months]
AUC from time zero to infinity (AUC[0-infinity]) of single dosing of GSK4381562 [Up to 27 months]
AUC(0-infinity) of single dosing of GSK4381562 in combination with dostarlimab [Up to 27 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

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
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Dallas	Texas	United States	75230
2	GSK Investigational Site	San Antonio	Texas	United States	78229
3	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2M9