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Active, Not Recruiting

NCT Number: NCT04446351

Study of the Safety and Effectiveness of GSK6097608 in Participants With Advanced Solid Tumors

This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants with advanced solid tumors. In addition, dostarlimab will be given as monotherapy (Arm D); and in combination with belrestotug (Arm E); and with GSK6097608 + belrestotug (Arm F) in Japanese and Chinese participants. The study may assess the PK/PD cohorts for Arm E and/or Arm F in participants outside of China and Japan. Additionally, dostarlimab will be given in combination with cobolimab in Japanese participants. Drug name mentioned as belrestotug, GSK4428859A and EOS884448 are interchangeable for the same compound. In the rest of the document, the drug will be referred to as belrestotug.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site, Ottawa, Ontario, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults 18 years of age or older (or >=20 years of age in Arm-A Japan, Arm-D Japan, Arm E-Japan, Arm F-Japan, and Arm G-Japan)
  • Female participants of childbearing potential must agree to use a highly effective form of contraception
  • Histological or cytological documentation of locally advanced, recurrent, or metastatic solid malignancy. Enrollment in PK/PD cohorts will be restricted to participants with histologically or cytologically confirmed diagnosis of 1 or more of the following: non-small-cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), endometrial cancer (EC), colorectal cancer (CRC) (including specified molecular subtypes of these) or an alternative immunogenic tumor type with medical monitor approval
  • 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
  • Participants in a PK/PD cohort (Arms A, B, E and F) must provide fresh tumor biopsies. Biopsies are not required from participants enrolled in Arm D, Arm E, (non-PK/PD cohorts only), Arm F (non-PK/PD cohort only), Arm G or any participant enrolled in mainland China
  • Eastern cooperative oncology group (ECOG) performance status (PS) 0 to 1
  • Life expectancy of at least 12 weeks
  • Adequate organ function as determined by laboratory assessments
  • Adequate cardiac ejection fraction as measured by echocardiogram
  • Arm A-Japan, Arm D-Japan, Arm E-Japan, Arm F-Japan, and Arm G-Japan only: lives in Japan and is racially Japanese, defined as all biological grandparents being Japanese
  • Arm A-China, Arm B-China, Arm D-China, Arm E-China and Arm F-China only (excluding PK/PD cohorts in Arm E and Arm F): is of Chinese descent and lives in China
  • Arm D, Arm E, Arm F, and Arm G only: has been deemed suitable for assigned treatment based on assessment by the investigator

Exclusion criteria

  • Prior anti-cancer treatment including investigational agents, immune checkpoint inhibitors, chemotherapy, targeted therapy, and biological therapy: within 4 weeks or 5 half-lives of the drug, 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; or history of myocarditis of any grade during a previous treatment with immunotherapy
  • Known additional malignancy that progressed or required active treatment within the last 2 years
  • Uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years
  • Concurrent medical condition requiring the use of systemic immunosuppressive treatment
  • Cirrhosis or current unstable liver or biliary disease per investigator assessment
  • Active infection requiring systemic treatment, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
  • Prolonged QT as measured by electrocardiogram
  • Allergen desensitization therapy within 4 weeks of starting study intervention
  • History of hypersensitivity to any of the study interventions or their excipients
  • Has a history or evidence of cardiac abnormalities within the 6 months prior to enrolment
  • Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions
  • History of idiopathic pulmonary fibrosis; interstitial lung disease; organizing pneumonia; noninfectious pneumonitis that required steroids, or evidence of active, noninfectious pneumonitis
  • Pregnant or lactating woman
  • Receipt of live vaccine within 30 days of the start of study intervention
  • Receipt of transfusion of blood products or administration of colony-stimulating factors within 14 days before the first dose of study intervention
  • Major surgery less than 4 weeks before the first dose of study intervention
  • Known drug or alcohol abuse

Treatment and study plan

GSK6097608

Drug

GSK6097608 will be administered as an IV infusion.

Dostarlimab

Drug

Dostarlimab will be administered as an IV infusion.

Cobolimab

Drug

Cobolimab will be administered as an IV infusion.

Belrestotug

Drug

Belrestotug will be administered as an IV infusion.

Other names: GSK4428859A, EOS884448

Primary outcomes

  1. Number of participants with dose-limiting toxicities (DLTs)

    Time frame: Up to Day 21

  2. Number of participants with adverse events (AEs) and serious adverse events (SAEs)

    Time frame: Up to 2 years

Secondary outcomes

  1. Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings

    Time frame: Up to 2 years

  2. Number of participants with dose reductions or delay

    Time frame: Up to 2 years

  3. Number of participants withdrawn due to AEs

    Time frame: Up to 2 years

  4. Overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Time frame: Up to 2 years

  5. Arms D, E, F, G: ORR based on modified Response Evaluation Criteria in Solid Tumors (iRECIST)

    Time frame: Up to 2 years

  6. Arms D, E, F, G: Disease Control Rate (DCR) based on RECIST 1.1

    Time frame: Up to 2 years

  7. Arms D, E, F, G: DCR based on iRECIST

    Time frame: Up to 2 years

  8. Arms D, E, F, G: Time to response (TTR) based on RECIST 1.1

    Time frame: Up to 2 years

  9. Arms D, E, F, G: TTR based on iRECIST

    Time frame: Up to 2 years

  10. Arms D, E, F, G: Duration of response (DOR) based on RECIST 1.1

    Time frame: Up to 2 years

  11. Arms D, E, F, G: DOR based on iRECIST

    Time frame: Up to 2 years

  12. Arms D, E, F, G: Progression-free survival (PFS) based on RECIST 1.1

    Time frame: Up to 2 years

  13. Arms D, E, F, G: PFS based on iRECIST

    Time frame: Up to 2 years

  14. Arms A, B, F: Number of participants with positive anti-drug antibodies (ADAs) against GSK6097608

    Time frame: Up to 2 years

  15. Arms A, B, F: Titers of ADAs against GSK6097608

    Time frame: Up to 2 years

  16. Arms B, D, E, F, G: Number of participants with positive ADAs against dostarlimab

    Time frame: Up to 2 years

  17. Arms B, D, E, F, G: Titers of ADAs against dostarlimab

    Time frame: Up to 2 years

  18. Arms E, F: Number of participants with positive ADAs against belrestotug

    Time frame: Up to 2 years

  19. Arms E, F: Titers of ADAs against belrestotug

    Time frame: Up to 2 years

  20. Arm G: Number of participants with positive ADAs against cobolimab

    Time frame: Up to 2 years

  21. Arm G: Titers of ADAs against cobolimab

    Time frame: Up to 2 years

  22. Arms A, B, F: Maximum observed concentration (Cmax) for GSK6097608

    Time frame: Up to 2 years

  23. Arms A, B, F: Minimum observed concentration (Cmin) for GSK6097608

    Time frame: Up to 2 years

  24. Arms A, B, F: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-infinity]) for GSK6097608

    Time frame: Up to 2 years

  25. Arms A, B, F: Area under the plasma concentration-time curve from time zero to time (AUC[0-t]) for GSK6097608

    Time frame: Up to 2 years

  26. Arms A, B, F: Apparent terminal phase half-life (t1/2) for GSK6097608

    Time frame: Up to 2 years

  27. Arms B, D, E, F, G: Cmax for dostarlimab

    Time frame: Up to 2 years

  28. Arms B, D, E, F, G: Cmin for dostarlimab

    Time frame: Up to 2 years

  29. Arms B, D, E, F, G: AUC(0-infinity) for dostarlimab

    Time frame: Up to 2 years

  30. Arms B, D, E, F, G: AUC(0-t) for dostarlimab

    Time frame: Up to 2 years

  31. Arms B, D, E, F, G: t1/2 for dostarlimab

    Time frame: Up to 2 years

  32. Arms E, F: Cmax for belrestotug

    Time frame: Up to 2 years

  33. Arms E, F: Cmin for belrestotug

    Time frame: Up to 2 years

  34. Arms E, F: AUC(0-infinity) for belrestotug

    Time frame: Up to 2 years

  35. Arms E, F: AUC(0-t) for belrestotug

    Time frame: Up to 2 years

  36. Arms E, F: t1/2 for belrestotug

    Time frame: Up to 2 years

  37. Arm G: Cmax for cobolimab

    Time frame: Up to 2 years

  38. Arm G: Cmin for cobolimab

    Time frame: Up to 2 years

  39. Arm G: AUC(0-infinity) for cobolimab

    Time frame: Up to 2 years

  40. Arm G: AUC(0-t) for cobolimab

    Time frame: Up to 2 years

  41. Arm G: t1/2 for cobolimab

    Time frame: Up to 2 years

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Collaborators

  • 23andMe, Inc.
  • iTeos Therapeutics

Registry information

Official study title

A Phase 1 First-Time-in-Human, Open-Label Study of GSK6097608 Administered as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors

Important dates

Study start
2020
Primary completion
2026
Study completion
2026
First posted
Jun 24, 2020
Registry last updated
Oct 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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