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

Phase 1RecruitingNCT05277051

GlaxoSmithKline158 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

158

Conditions

Neoplasms

Interventions

RemzistotugDRUG

Remzistotug will be administered.

DostarlimabDRUG

Dostarlimab will be administered.

BelrestotugDRUG

Belrestotug will be administered.

Nelistotug

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (26)

GSK Investigational Site

Outcomes

Primary Outcomes

Arms A, B, C, I: Number of Participants with dose-limiting toxicities (DLTs)

Time frame: Up to 21 days

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Up to 27 months

Secondary Outcomes

Number of Participants With Clinically Significant Changes in Laboratory Parameters, Electrocardiogram (ECG) and Vital Signs

Time frame: Up to 24 months

Number of Participants With Dose Reductions or Delays

Time frame: Up to 24 months

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.

Time frame: Up to 27 months

Overall Response Rate (ORR)

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.

Time frame: Up to 24 months

Number of Participants With Positive Antidrug Antibodies (ADA) to remzistotug

Time frame: Up to 27 months

Titres of ADA to remzistotug

Time frame: Up to 27 months

Number of Participants With Positive ADA to Dostarlimab

Central Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718 GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Nelistotug will be administered.

GSK5764227DRUG

GSK5764227 will be administered.

San Francisco, California, United States

GSK Investigational Site

Charlotte, North Carolina, United States

RECRUITING

GSK Investigational Site

Oklahoma City, Oklahoma, United States

RECRUITING

GSK Investigational Site

Philadelphia, Pennsylvania, United States

RECRUITING

GSK Investigational Site

Dallas, Texas, United States

RECRUITING

GSK Investigational Site

San Antonio, Texas, United States

RECRUITING

GSK Investigational Site

Salt Lake City, Utah, United States

RECRUITING

GSK Investigational Site

Nedlands, Western Australia, Australia

RECRUITING

GSK Investigational Site

Ottawa, Ontario, Canada

RECRUITING

GSK Investigational Site

Toronto, Ontario, Canada

RECRUITING

...and 16 more locations

Time frame: Up to 27 months

Titers of ADA to Dostarlimab

Time frame: Up to 27 months

Number of Participants With Positive ADA to belrestotug

Time frame: Up to 27 months

Titers of ADA to belrestotug

Time frame: Up to 27 months

Number of Participants With Positive ADA to nelistotug

Time frame: Up to 27 months

Titers of ADA to nelistotug

Time frame: Up to 27 months

Number of Participants With Positive ADA to GSK5764227

Time frame: Up to 27 months

Titers of ADA to GSK5764227

Time frame: Up to 27 months

Serum Concentrations of remzistotug

Time frame: Up to 4 months

Serum Concentrations of dostarlimab

Time frame: Up to 4 months

Serum Concentrations of belrestotug

Time frame: Up to 4 months

Serum Concentrations of nelistotug

Time frame: Up to 4 months

Serum Concentrations of GSK5764227

Time frame: Up to 4 months

Maximum Observed Plasma Concentration (Cmax) of remzistotug Monotherapy

Time frame: Up to 27 months

Cmax of remzistotug in Combination With Dostarlimab

Time frame: Up to 27 months

Cmax of remzistotug in Combination With dostarlimab and belrestotug

Time frame: Up to 27 months

Cmax following administration of dostarlimab with belrestotug

Time frame: Up to 27 months

Minimum Observed Plasma Concentration (Cmin) of remzistotug Monotherapy

Time frame: Up to 27 months

Cmin of remzistotug in Combination With Dostarlimab

Time frame: Up to 27 months

Cmin of remzistotug in Combination With dostarlimab and belrestotug

Time frame: Up to 27 months

Cmin following administration of dostarlimab with belrestotug

Time frame: Up to 27 months

Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of remzistotug

Time frame: Up to 27 months

AUC(0-t) of remzistotug in Combination With Dostarlimab

Time frame: Up to 27 months

AUC(0-t) of remzistotug in Combination With dostarlimab and belrestotug

Time frame: Up to 27 months

AUC(0-t) following administration of dostarlimab with belrestotug

Time frame: Up to 27 months

AUC From Time Zero to Infinity (AUC[0-infinity]) of Single Dosing of remzistotug

Time frame: Up to 27 months

AUC(0-infinity) of Single Dosing of remzistotug in Combination with Dostarlimab

Time frame: Up to 27 months

AUC(0-infinity) of Single Dosing of remzistotug in Combination With dostarlimab and belrestotug

Time frame: Up to 27 months

AUC(0-infinity) of Single Dosing of remzistotug following administration of dostarlimab with belrestotug

Time frame: Up to 27 months

Cmax of dostarlimab in Combination With remzistotug

Time frame: Up to 27 months

Cmax of dostarlimab in combination with GSK5764227

Time frame: Up to 27 months

Cmax of dostarlimab in combination with remzistotug and belrestotug

Time frame: Up to 27 months

Cmax of dostarlimab in combination with belrestotug

Time frame: Up to 27 months

Cmax of dostarlimab in combination with belrestotug and remzistotug

Time frame: Up to 27 months

Cmax of dostarlimab in combination with belrestotug and nelistotug

Time frame: Up to 27 months

China cohort: Cmax of dostarlimab monotherapy

Time frame: Up to 18 months

Cmin of dostarlimab in Combination With remzistotug

Time frame: Up to 27 months

Cmin of dostarlimab in combination with GSK5764227

Time frame: Up to 18 months

Cmin of dostarlimab in combination with remzistotug and belrestotug

Time frame: Up to 27 months

Cmin of dostarlimab in combination with belrestotug

Time frame: Up to 27 months

Cmin of dostarlimab in combination with belrestotug and remzistotug

Time frame: Up to 27 months

Cmin of dostarlimab in combination with belrestotug and nelistotug

Time frame: Up to 27 months

China cohort: Cmin of dostarlimab monotherapy

Time frame: Up to 18 months

AUC(0-t) of dostarlimab in Combination With remzistotug

Time frame: Up to 27 months

AUC(0-t) of dostarlimab in combination with GSK5764227

Time frame: Up to 18 months

AUC(0-t) of dostarlimab in combination with remzistotug and belrestotug

Time frame: Up to 27 months

AUC(0-t) of dostarlimab in combination with belrestotug

Time frame: Up to 27 months

AUC(0-t) of dostarlimab in combination with belrestotug and remzistotug

Time frame: Up to 27 months

AUC(0-t) of dostarlimab in combination with belrestotug and nelistotug

Time frame: Up to 27 months

China cohort: AUC(0-t) of dostarlimab monotherapy

Time frame: Up to 18 months

AUC(0-infinity) of dostarlimab in Combination With remzistotug

Time frame: Up to 27 months

AUC(0-infinity) of dostarlimab in combination with GSK5764227

Time frame: Up to 27 months

AUC(0-infinity) of dostarlimab in combination with remzistotug and belrestotug

Time frame: Up to 27 months

AUC(0-infinity) of dostarlimab in combination with belrestotug

Time frame: Up to 27 months

AUC(0-infinity) of dostarlimab in combination with belrestotug and remzistotug

Time frame: Up to 27 months

AUC(0-infinity) of dostarlimab in combination with belrestotug and nelistotug

Time frame: Up to 27 months

China cohort: AUC(0-infinity) of dostarlimab monotherapy

Time frame: Up to 18 months

T1/2 of dostarlimab in Combination With remzistotug

Time frame: Up to 27 months

T1/2 of dostarlimab in combination with GSK5764227

Time frame: Up to 18 months

China cohort: T1/2 of dostarlimab monotherapy

Time frame: Up to 18 months

Cmax of belrestotug in combination with dostarlimab and belrestotug

Time frame: Up to 27 months

Cmax of belrestotug in combination with dostarlimab

Time frame: Up to 27 months

Cmax of belrestotug in combination with dostarlimab and remzistotug

Time frame: Up to 27 months

Cmax of belrestotug in combination with dostarlimab and nelistotug

Time frame: Up to 27 months

Cmin of belrestotug in combination with dostarlimab and belrestotug

Time frame: Up to 27 months

Cmin of belrestotug in combination with dostarlimab

Time frame: Up to 27 months

Cmin of belrestotug in combination with dostarlimab and remzistotug

Time frame: Up to 27 months

Cmin of belrestotug in combination with dostarlimab and nelistotug

Time frame: Up to 27 months

AUC (0-t) of belrestotug in combination with dostarlimab and belrestotug

Time frame: Up to 27 months

AUC (0-t) of belrestotug in combination with dostarlimab

Time frame: Up to 27 months

AUC (0-t) of belrestotug in combination with dostarlimab and remzistotug

Time frame: Up to 27 months

AUC (0-t) of belrestotug in combination with dostarlimab and nelistotug

Time frame: Up to 27 months

AUC (0-infinity) of belrestotug in combination with dostarlimab and belrestotug

Time frame: Up to 27 months

AUC (0- infinity) of belrestotug in combination with dostarlimab

Time frame: Up to 27 months

AUC (0- infinity) of belrestotug in combination with dostarlimab and remzistotug

Time frame: Up to 27 months

AUC (0- infinity) of belrestotug in combination with dostarlimab and nelistotug

Time frame: Up to 27 months

Cmax of nelistotug in combination with dostarlimab and belrestotug

Time frame: Up to 27 months

Cmin of nelistotug in combination with dostarlimab and belrestotug

Time frame: Up to 27 months

AUC (0-t) of nelistotug in combination with dostarlimab and belrestotug

Time frame: Up to 27 months

AUC (0-infinity) of nelistotug in combination with dostarlimab and belrestotug

Time frame: Up to 27 months

Cmax of GSK5764227 in combination with dostarlimab

Time frame: Up to 18 months

Cmin of GSK5764227 in combination with dostarlimab

Time frame: Up to 18 months

AUC (0-t) of GSK5764227 conjugated Ab in combination with dostarlimab

Time frame: Up to 18 months

AUC (0-t) of GSK5764227 small molecule toxin in combination with dostarlimab

Time frame: Up to 18 months

AUC (0-infinity) of GSK5764227 conjugated Ab in combination with dostarlimab

Time frame: Up to 18 months

AUC (0-infinity) of GSK5764227 small molecule toxin in combination with dostarlimab

Time frame: Up to 18 months