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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05277051
Recruitment Status : Recruiting
First Posted : March 14, 2022
Last Update Posted : November 23, 2022
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Neoplasms Drug: GSK4381562 Drug: Dostarlimab Drug: GSK4428859A Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 3 Dose Escalation arms (GSK4381562 alone and GSK4381562 plus dostarlimab and GSK4381562 plus dostarlimab plus GSK4428859A); additional participants may be enrolled in any 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 : March 22, 2022
Estimated Primary Completion Date : December 29, 2025
Estimated Study Completion Date : December 29, 2025


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.

Experimental: Participants receiving GSK4381562 plus dostarlimab plus GSK4428859A Drug: GSK4381562
GSK4381562 will be administered.

Drug: Dostarlimab
Dostarlimab will be administered.

Drug: GSK4428859A
GSK4428859A will be administered.




Primary Outcome Measures :
  1. Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: Up to 21 days ]
  2. Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 27 months ]

Secondary Outcome Measures :
  1. Number of participants with clinically significant changes in laboratory parameters, electrocardiogram (ECG) and vital signs [ Time Frame: Up to 24 months ]
  2. Number of participants with dose reductions or delays [ Time Frame: Up to 24 months ]
  3. 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.

  4. 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.

  5. Number of participants with positive antidrug antibodies (ADA) to GSK4381562 [ Time Frame: Up to 27 months ]
  6. Titers of ADA to GSK4381562 [ Time Frame: Up to 27 months ]
  7. Number of participants with positive ADA to dostarlimab [ Time Frame: Up to 27 months ]
  8. Titers of ADA to dostarlimab [ Time Frame: Up to 27 months ]
  9. Number of participants with positive ADA to GSK4428859A [ Time Frame: Up to 27 months ]
  10. Titers of ADA to GSK4428859A [ Time Frame: Up to 27 months ]
  11. Plasma concentrations of GSK4381562 [ Time Frame: Up to 4 months ]
  12. Maximum observed plasma concentration (Cmax) of GSK4381562 monotherapy [ Time Frame: Up to 27 months ]
  13. Cmax of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
  14. Cmax of GSK4381562 in combination with GSK4428859A [ Time Frame: Up to 27 months ]
  15. Minimum observed plasma concentration (Cmin) of GSK4381562 monotherapy [ Time Frame: Up to 27 months ]
  16. Cmin of GSK4381562 in combination with dostarlimab [ Time Frame: UP to 27 months ]
  17. Cmin of GSK4381562 in combination with GSK4428859A [ Time Frame: Up to 27 months ]
  18. 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 ]
  19. AUC(0-t) of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
  20. AUC(0-t) of GSK4381562 in combination with GSK4428859A [ Time Frame: Up to 27 months ]
  21. AUC from time zero to infinity (AUC[0-infinity]) of single dosing of GSK4381562 [ Time Frame: Up to 27 months ]
  22. AUC(0-infinity) of single dosing of GSK4381562 in combination with dostarlimab [ Time Frame: Up to 27 months ]
  23. AUC(0-infinity) of single dosing of GSK4381562 in combination with GSK4428859A [ Time Frame: Up to 27 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05277051


Contacts
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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

Locations
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United States, Pennsylvania
GSK Investigational Site Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Anthony J Olszanski         
United States, Texas
GSK Investigational Site Recruiting
Dallas, Texas, United States, 75230
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Reva Elaine Schneider         
GSK Investigational Site Recruiting
San Antonio, Texas, United States, 78229
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Drew W Rasco         
Canada, Ontario
GSK Investigational Site Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: John Hilton         
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Lillian Siu         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT05277051    
Other Study ID Numbers: 217228
2021-004968-95 ( EudraCT Number )
First Posted: March 14, 2022    Key Record Dates
Last Update Posted: November 23, 2022
Last Verified: November 2022
Individual Participant Data (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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Advanced solid tumors
Metastatic solid tumor
Anticancer agents
Dostarlimab
GSK4381562
GSK4428859A
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)