First-Time-in-Human Study of GSK4381562 in Participants With Advanced Solid Tumors
Phase 1
Recruiting
- Conditions
- Neoplasms
- Interventions
- Registration Number
- NCT05277051
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 141
Inclusion Criteria
Not provided
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description China Cohort: Participants receiving dostarlimab plus belrestotug (Arm H) Belrestotug - Participants receiving GSK4381562 plus dostarlimab (Arm B) GSK4381562 - Participants receiving GSK4381562 plus dostarlimab (Arm B) Dostarlimab - Participants receiving GSK4381562 plus dostarlimab plus belrestotug (Arm C) GSK4381562 - Participants receiving GSK4381562 plus dostarlimab plus belrestotug (Arm C) Dostarlimab - Participants receiving GSK4381562 plus dostarlimab plus belrestotug (Arm C) Belrestotug - Participants receiving dostarlimab plus belrestotug (Arm D) Dostarlimab - Participants receiving dostarlimab plus belrestotug (Arm D) Belrestotug - Participants receiving dostarlimab plus belrestotug plus GSK4381562 (Arm E) GSK4381562 - Participants receiving dostarlimab plus belrestotug plus GSK4381562 (Arm E) Dostarlimab - Participants receiving dostarlimab plus belrestotug plus GSK4381562 (Arm E) Belrestotug - Participants receiving dostarlimab plus belrestotug plus nelistotug (Arm F) Dostarlimab - Participants receiving dostarlimab plus belrestotug plus nelistotug (Arm F) Belrestotug - Participants receiving dostarlimab plus belrestotug plus nelistotug (Arm F) Nelistotug - China Cohort: Participants receiving dostarlimab (Arm G) Dostarlimab - China Cohort: Participants receiving dostarlimab plus belrestotug (Arm H) Dostarlimab - Participants receiving GSK5764227 plus dostarlimab (Arm I) Dostarlimab - Participants receiving GSK5764227 plus dostarlimab (Arm I) GSK5764227 - Participants receiving GSK4381562 monotherapy (Arm A) GSK4381562 -
- Primary Outcome Measures
Name Time Method 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
Name Time Method AUC(0-infinity) of Single Dosing of GSK4381562 in Combination With dostarlimab and belrestotug Up to 27 months AUC(0-infinity) following administration of dostarlimab with belrestotug Up to 27 months AUC(0-t) of dostarlimab in combination with belrestotug and nelistotug Up to 27 months AUC (0-t) of belrestotug in combination with dostarlimab and GSK4381562 Up to 27 months China cohort: AUC (0- infinity) of belrestotug in combination with dostarlimab Up to 27 months China cohort: t1/2 of belrestotug in combination with dostarlimab Up to 27 months Cmax 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 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 Overall Response Rate (ORR) Up to 24 months 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.
Number of Participants With Positive Antidrug Antibodies (ADA) to GSK4381562 Up to 27 months Titres 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 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 GSK4381562 Up to 4 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 AUC (0-t) of belrestotug in combination with dostarlimab followed by GSK4381562 Up to 27 months Cmax of dostarlimab in Combination With GSK4381562 Up to 27 months Cmax of dostarlimab in combination with GSK5764227 Up to 27 months Cmax of dostarlimab in combination with GSK4381562 followed by belrestotug Up to 27 months Cmax of dostarlimab in combination with belrestotug Up to 27 months Cmax of dostarlimab in combination with belrestotug and GSK4381562 Up to 27 months Cmax of dostarlimab in combination with belrestotug and nelistotug Up to 27 months China cohort: Cmax of dostarlimab monotherapy Up to 27 months China cohort: Cmax of dostarlimab in combination with belrestotug Up to 27 months Cmin of dostarlimab in Combination With GSK4381562 Up to 27 months Cmin of dostarlimab in combination with GSK5764227 Up to 27 months Cmin of dostarlimab in combination with GSK4381562 followed by belrestotug Up to 27 months Cmin of dostarlimab in combination with belrestotug Up to 27 months Cmin of dostarlimab in combination with belrestotug and GSK4381562 Up to 27 months Cmin of dostarlimab in combination with belrestotug and nelistotug Up to 27 months China cohort: Cmin of dostarlimab monotherapy Up to 27 months China cohort: Cmin of dostarlimab in combination with belrestotug Up to 27 months AUC(0-t) of dostarlimab in Combination With GSK4381562 Up to 27 months AUC(0-t) of dostarlimab in combination with GSK5764227 Up to 27 months AUC(0-t) of dostarlimab in combination with GSK4381562 followed by belrestotug 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 GSK4381562 Up to 27 months AUC(0-infinity) of Single Dosing of GSK4381562 in Combination with Dostarlimab Up to 27 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.
Serum Concentrations of GSK5764227 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 Cmax of GSK4381562 in Combination With dostarlimab and belrestotug Up to 27 months Cmax following administration of dostarlimab with belrestotug 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 Cmin of GSK4381562 in Combination With dostarlimab and belrestotug Up to 27 months Cmin following administration of dostarlimab with belrestotug 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(0-t) of GSK4381562 in Combination With dostarlimab and belrestotug Up to 27 months AUC(0-t) following administration of dostarlimab with belrestotug Up to 27 months AUC From Time Zero to Infinity (AUC[0-infinity]) of Single Dosing of GSK4381562 Up to 27 months China cohort: t1/2 of dostarlimab in combination with belrestotug Up to 27 months Cmax of belrestotug in combination with dostarlimab followed by GSK4381562 Up to 27 months Cmax of belrestotug in combination with dostarlimab Up to 27 months Cmax of belrestotug in combination with dostarlimab and GSK4381562 Up to 27 months Cmax of belrestotug in combination with dostarlimab and nelistotug Up to 27 months China cohort: Cmax of belrestotug in combination with dostarlimab Up to 27 months Cmin of belrestotug in combination with dostarlimab followed by GSK4381562 Up to 27 months Cmin of belrestotug in combination with dostarlimab Up to 27 months Cmin of GSK5764227 in combination with dostarlimab Up to 27 months AUC (0-t) of GSK5764227 conjugated antibody (Ab) in combination with dostarlimab Up to 27 months AUC (0-infinity) of GSK5764227 small molecule toxin in combination with dostarlimab Up to 27 months China cohort: AUC(0-t) of dostarlimab monotherapy Up to 27 months China cohort: AUC(0-t) of dostarlimab in combination with belrestotug Up to 27 months AUC(0-infinity) of dostarlimab in Combination With GSK4381562 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 GSK4381562 followed by belrestotug 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 GSK4381562 Up to 27 months AUC(0-infinity) of dostarlimab in combination with belrestotug and nelistotug Up to 27 months China cohort: AUC(0-infinity) of dostarlimab monotherapy Up to 27 months China cohort: AUC(0-infinity) of dostarlimab in combination with belrestotug Up to 27 months Mean terminal half-life (t1/2) of dostarlimab in Combination With GSK4381562 Up to 27 months Mean terminal half-life (t1/2) of dostarlimab in combination with GSK5764227 Up to 27 months China cohort: t1/2 of dostarlimab monotherapy Up to 27 months Cmin of belrestotug in combination with dostarlimab and GSK4381562 Up to 27 months Cmin of belrestotug in combination with dostarlimab and nelistotug Up to 27 months China cohort: Cmin of belrestotug in combination with dostarlimab 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 China cohort: AUC (0-t) of belrestotug in combination with dostarlimab Up to 27 months AUC (0-infinity) of belrestotug in combination with dostarlimab followed by GSK4381562 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 GSK4381562 Up to 27 months AUC (0- infinity) of belrestotug in combination with dostarlimab and nelistotug Up to 27 months Cmin 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 Cmax of GSK5764227 in combination with dostarlimab Up to 27 months AUC (0-t) of GSK5764227 small molecule toxin in combination with dostarlimab Up to 27 months AUC (0-infinity) of GSK5764227 conjugated Ab in combination with dostarlimab Up to 27 months
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Sutton, United Kingdom
GSK Investigational Site🇬🇧Sutton, United KingdomUS GSK Clinical Trials Call CenterContact877-379-3718GSKClinicalSupportHD@gsk.comEU GSK Clinical Trials Call CentreContact+44 (0) 20 8990 4466GSKClinicalSupportHD@gsk.comPamela N. MunsterPrincipal InvestigatorAntoinette TanPrincipal InvestigatorDebra L. RichardsonPrincipal InvestigatorAnthony J OlszanskiPrincipal InvestigatorReva Elaine SchneiderPrincipal InvestigatorDrew W RascoPrincipal InvestigatorVaia FlorouPrincipal InvestigatorSamantha BowyerPrincipal InvestigatorJohn HiltonPrincipal InvestigatorLillian SiuPrincipal InvestigatorYintao LiPrincipal InvestigatorYe GuoPrincipal InvestigatorFrancois GhiringhelliPrincipal InvestigatorLoic LebellecPrincipal InvestigatorToshihiko DoiPrincipal InvestigatorNoboru YamamotoPrincipal InvestigatorDong-Wan KimPrincipal InvestigatorByoung Chul ChoPrincipal InvestigatorElena Garralda CabanasPrincipal InvestigatorVictor Moreno GarcíaPrincipal InvestigatorMaría José de Miguel LukenPrincipal InvestigatorJavier García CorbachoPrincipal InvestigatorNatalie CookPrincipal InvestigatorJohann S De BonoPrincipal Investigator