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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms
• Intervention / Treatment: Drug: GSK6097608; Drug: Dostarlimab; Drug: Cobolimab; Drug: Belrestotug

• Study Type: Interventional
• Enrollment (Estimated): 244
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Scott A Laurie
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Lillian Siu
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
• Japan
  • Chiba, Japan, 277-8577
    • Recruiting
    • GSK Investigational Site
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Principal Investigator: Yoshitaka Zenke
  • Tokyo, Japan, 104-0045
    • Recruiting
    • GSK Investigational Site
    • Principal Investigator: Noboru Yamamoto
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • GSK Investigational Site
    • Principal Investigator: Dong-Wan Kim
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • GSK Investigational Site
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Principal Investigator: Myung-Ju Ahn
• United States
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • GSK Investigational Site
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
      • Principal Investigator: Omid Hamid
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Frank Stephen Hodi
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Reva Elaine Schneider
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Houston, Texas, United States, 77030-4009
      • Recruiting
      • GSK Investigational Site
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
      • Principal Investigator: Jordi Rodon Ahnert
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Drew W Rasco
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants receiving GSK6097608 monotherapy (Arm A); Participants will be administered an intravenous (IV) infusion of GSK6097608 every 3 weeks as monotherapy in escalating doses.	Drug: GSK6097608; GSK6097608 will be administered as an IV infusion.
Experimental: Participants receiving GSK6097608 plus dostarlimab (Arm B); Participants will be administered IV infusion of GSK6097608 every 3 weeks in escalating doses followed by dostarlimab.	Drug: GSK6097608; GSK6097608 will be administered as an IV infusion.; Drug: Dostarlimab; Dostarlimab will be administered as an IV infusion.
Experimental: Participants receiving dostarlimab monotherapy (Arm D); Participants will be administered an IV infusion of dostarlimab monotherapy (1 cohort will receive dostarlimab every 3 weeks and 1 cohort will receive dostarlimab every 6 weeks).	Drug: Dostarlimab; Dostarlimab will be administered as an IV infusion.
Experimental: Participants receiving dostarlimab plus cobolimab (Arm G); Participants will be administered an IV infusion of cobolimab followed by dostarlimab	Drug: Dostarlimab; Dostarlimab will be administered as an IV infusion.; Drug: Cobolimab; Cobolimab will be administered as an IV infusion.
Experimental: Participants receiving dostarlimab plus belrestotug (Arm E); Participants will be administered IV infusions of dostarlimab followed by belrestotug, every 3 weeks.	Drug: Dostarlimab; Dostarlimab will be administered as an IV infusion.; Drug: Belrestotug; Belrestotug will be administered as an IV infusion.; Other Names: EOS884448; GSK4428859A
Experimental: Participants receiving dostarlimab plus belrestotug plus GSK6097608 (Arm F); Participants will be administered an IV infusion of dostarlimab followed by belrestotug followed by GSK6097608 every 3 weeks.	Drug: GSK6097608; GSK6097608 will be administered as an IV infusion.; Drug: Dostarlimab; Dostarlimab will be administered as an IV infusion.; Drug: Belrestotug; Belrestotug will be administered as an IV infusion.; Other Names: EOS884448; GSK4428859A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with dose-limiting toxicities (DLTs)	Up to Day 21
Number of participants with adverse events (AEs) and serious adverse events (SAEs)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings	Up to 2 years
Number of participants with dose reductions or delay	Up to 2 years
Number of participants withdrawn due to AEs	Up to 2 years
Overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to 2 years
Arms A, B, F: Number of participants with positive anti-drug antibodies (ADAs) against GSK6097608	Up to 2 years
Arms A, B, F: Titers of ADAs against GSK6097608	Up to 2 years
Arms A, B, F: Maximum observed concentration (Cmax) for GSK6097608	Up to 2 years
Arms A, B, F: Minimum observed concentration (Cmin) for GSK6097608	Up to 2 years
Arms A, B, F: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-infinity]) for GSK6097608	Up to 2 years
Arms A, B, F: Area under the plasma concentration-time curve from time zero to time (AUC[0-t]) for GSK6097608	Up to 2 years
Arms A, B, F: Apparent terminal phase half-life (t1/2) for GSK6097608	Up to 2 years
Arms D, E, F, G: ORR based on modified Response Evaluation Criteria in Solid Tumors (iRECIST)	Up to 2 years
Arms D, E, F, G: Disease Control Rate (DCR) based on RECIST 1.1	Up to 2 years
Arms D, E, F, G: DCR based on iRECIST	Up to 2 years
Arms D, E, F, G: Time to response (TTR) based on RECIST 1.1	Up to 2 years
Arms D, E, F, G: TTR based on iRECIST	Up to 2 years
Arms D, E, F, G: Duration of response (DOR) based on RECIST 1.1	Up to 2 years
Arms D, E, F, G: DOR based on iRECIST	Up to 2 years
Arms D, E, F, G: Progression-free survival (PFS) based on RECIST 1.1	Up to 2 years
Arms D, E, F, G: PFS based on iRECIST	Up to 2 years
Arms B, D, E, F, G: Number of participants with positive ADAs against dostarlimab	Up to 2 years
Arms B, D, E, F, G: Titers of ADAs against dostarlimab	Up to 2 years
Arm G: Number of participants with positive ADAs against cobolimab	Up to 2 years
Arm G: Titers of ADAs against cobolimab	Up to 2 years
Arms B, D, E, F, G: Cmax for dostarlimab	Up to 2 years
Arms B, D, E, F, G: Cmin for dostarlimab	Up to 2 years
Arms B, D, E, F, G: AUC(0-infinity) for dostarlimab	Up to 2 years
Arms B, D, E, F, G: AUC(0-t) for dostarlimab	Up to 2 years
Arms B, D, E, F, G: t1/2 for dostarlimab	Up to 2 years
Arm G: Cmax for cobolimab	Up to 2 years
Arm G: Cmin for cobolimab	Up to 2 years
Arm G: AUC(0-infinity) for cobolimab	Up to 2 years
Arm G: AUC(0-t) for cobolimab	Up to 2 years
Arm G: t1/2 for cobolimab	Up to 2 years
Arms E, F: Number of participants with positive ADAs against belrestotug	Up to 2 years
Arms E, F: Titers of ADAs against belrestotug	Up to 2 years
Arms E, F: Cmax for belrestotug	Up to 2 years
Arms E, F: Cmin for belrestotug	Up to 2 years
Arms E, F: AUC(0-infinity) for belrestotug	Up to 2 years
Arms E, F: AUC(0-t) for belrestotug	Up to 2 years
Arms E, F: t1/2 for belrestotug	Up to 2 years

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: 23andMe, Inc.; iTeos Therapeutics
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2020
• Primary Completion (Estimated): September 3, 2025
• Study Completion (Estimated): September 3, 2025

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: June 22, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 29, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; dostarlimab; First-time-in-human; Dose escalation; Pharmacodynamics; Advanced solid tumors; GSK6097608; GSK4428859A; EOS884448; belrestotug; cobolimab
• Additional Relevant MeSH Terms: Antineoplastic Agents; Dostarlimab
• Other Study ID Numbers: 212214

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No