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

• ClinicalTrials.gov Identifier: NCT05277051
• Recruitment Status: Recruiting
• First Posted: March 14, 2022
• Last Update Posted: January 11, 2024
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: March 3, 2022
• First Posted Date: March 14, 2022
• Last Update Posted Date: January 11, 2024
• Actual Study Start Date: March 22, 2022
• Estimated Primary Completion Date: October 14, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 9, 2024)

• Arms A, B, C: Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: Up to 21 days ]
• Arms A, B, C, D: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 27 months ]

Original Primary Outcome Measures (submitted: March 3, 2022)

• 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 ]
• Number of participants with AEs and SAEs by severity [ Time Frame: Up to 27 months ]
• Duration of AEs and SAEs [ Time Frame: Up to 27 months ]
  Reported only for the first occurrence of an immune-related adverse event. Duration will be expressed as the median number of days the symptom experienced.

Current Secondary Outcome Measures (submitted: January 9, 2024)

• 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Up to 27 months ]
• Titers of ADA to GSK4381562 [ Time Frame: Up to 27 months ]
• Number of participants with positive ADA to dostarlimab [ Time Frame: Up to 27 months ]
• Titers of ADA to dostarlimab [ Time Frame: Up to 27 months ]
• Number of participants with positive ADA to GSK4428859A [ Time Frame: Up to 27 months ]
• Titers of ADA to GSK4428859A [ Time Frame: Up to 27 months ]
• Serum concentrations of GSK4381562 [ Time Frame: Up to 4 months ]
• Serum concentrations of dostarlimab [ Time Frame: Up to 4 months ]
• Serum Concentrations of GSK4428859A [ Time Frame: Up to 4 months ]
• Maximum observed plasma concentration (Cmax) of GSK4381562 monotherapy [ Time Frame: Up to 27 months ]
• Cmax of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
• Cmax of GSK4381562 in combination with GSK4428859A [ Time Frame: Up to 27 months ]
• Cmax following administration of dostarlimab in combination with GSK4428859A [ Time Frame: Up to 27 months ]
• Minimum observed plasma concentration (Cmin) of GSK4381562 monotherapy [ Time Frame: Up to 27 months ]
• Cmin of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
• Cmin of GSK4381562 in combination with GSK4428859A [ Time Frame: Up to 27 months ]
• Cmin following administration of dostarlimab in combination with GSK4428859A [ 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 GSK4381562 [ Time Frame: Up to 27 months ]
• AUC(0-t) of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
• AUC(0-t) of GSK4381562 in combination with GSK4428859A [ Time Frame: Up to 27 months ]
• AUC(0-t) following administration of dostarlimab in combination with GSK4428859A [ Time Frame: Up to 27 months ]
• AUC from time zero to infinity (AUC[0-infinity]) of single dosing of GSK4381562 [ Time Frame: Up to 27 months ]
• AUC(0-infinity) of single dosing of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
• AUC(0-infinity) of single dosing of GSK4381562 in combination with GSK4428859A [ Time Frame: Up to 27 months ]
• AUC(0-infinity) following administration of dostarlimab in combination with GSK4428859A [ Time Frame: Up to 27 months ]

Original Secondary Outcome Measures (submitted: March 3, 2022)

• 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Up to 27 months ]
• Titers of ADA to GSK4381562 [ Time Frame: Up to 27 months ]
• Number of participants with positive ADA to dostarlimab [ Time Frame: Up to 27 months ]
• Titers of ADA to dostarlimab [ Time Frame: Up to 27 months ]
• Plasma concentrations of GSK4381562 [ Time Frame: Up to 4 months ]
• Maximum observed plasma concentration (Cmax) of GSK4381562 monotherapy [ Time Frame: Up to 27 months ]
• Cmax of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
• Minimum observed plasma concentration (Cmin) of GSK4381562 monotherapy [ Time Frame: Up to 27 months ]
• Cmin of GSK4381562 in combination with dostarlimab [ 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 GSK4381562 [ Time Frame: Up to 27 months ]
• AUC(0-t) of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
• AUC from time zero to infinity (AUC[0-infinity]) of single dosing of GSK4381562 [ Time Frame: Up to 27 months ]
• AUC(0-infinity) of single dosing of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First-Time-in-Human Study of GSK4381562 in Participants With Advanced Solid Tumors
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

3 Dose Escalation arms (Arm A: GSK4381562 alone; Arm B: GSK4381562 plus dostarlimab; Arm C: GSK4381562 plus dostarlimab plus GSK4428859A) and 1 new arm, Arm D (dostarlimab plus GSK4428859A). Additional participants may be enrolled in any study arms A, B or C 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

• Condition: Neoplasms

Intervention

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

Study Arms

• Experimental: Participants receiving GSK4381562 monotherapy (Arm A)
  Intervention: Drug: GSK4381562
• Experimental: Participants receiving GSK4381562 plus dostarlimab (Arm B)
  Interventions:

  • Drug: GSK4381562
  • Drug: Dostarlimab
• Experimental: Participants receiving GSK4381562 plus dostarlimab plus GSK4428859A (Arm C)
  Interventions:

  • Drug: GSK4381562
  • Drug: Dostarlimab
  • Drug: GSK4428859A
• Experimental: Participants receiving dostarlimab plus GSK4428859A (Arm D)
  Interventions:

  • Drug: Dostarlimab
  • Drug: GSK4428859A

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 18, 2022): 162
• Original Estimated Enrollment (submitted: March 3, 2022): 126
• Estimated Study Completion Date: October 14, 2026
• Estimated Primary Completion Date: October 14, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

• Listed Location Countries: Australia, Canada, China, France, Japan, Korea, Republic of, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05277051
• Other Study ID Numbers: 217228; 2021-004968-95 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (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.
• URL: http://clinicalstudydatarequest.com

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: January 2024