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

NCT04446351 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 212214
• Study Type: interventional
• Target: 107
• Locations: 4 countries
• Sites: 11

Brief Summary

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.

Conditions

Neoplasms

Keywords

GSK6097608; dostarlimab; Dose escalation; Pharmacokinetics; Pharmacodynamics; Advanced solid tumors; First-time-in-human; GSK4428859A; EOS884448; cobolimab; belrestotug

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (41)

• 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• Number of participants withdrawn due to AEs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 D, E, F, G: ORR based on modified Response Evaluation Criteria in Solid Tumors (iRECIST)

  Up to 2 years

Study Arms (6)

Participants receiving GSK6097608 monotherapy (Arm A)

EXPERIMENTAL

Participants will be administered an intravenous (IV) infusion of GSK6097608 every 3 weeks as monotherapy in escalating doses.

Drug: GSK6097608

Participants receiving GSK6097608 plus dostarlimab (Arm B)

EXPERIMENTAL

Participants will be administered IV infusion of GSK6097608 every 3 weeks in escalating doses followed by dostarlimab.

Drug: GSK6097608; Drug: Dostarlimab

Participants receiving dostarlimab monotherapy (Arm D)

EXPERIMENTAL

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

Participants receiving dostarlimab plus belrestotug (Arm E)

EXPERIMENTAL

Participants will be administered IV infusions of dostarlimab followed by belrestotug, every 3 weeks.

Drug: Dostarlimab; Drug: Belrestotug

Participants receiving dostarlimab plus belrestotug plus GSK6097608 (Arm F)

EXPERIMENTAL

Participants will be administered an IV infusion of dostarlimab followed by belrestotug followed by GSK6097608 every 3 weeks.

Drug: GSK6097608; Drug: Dostarlimab; Drug: Belrestotug

Participants receiving dostarlimab plus cobolimab (Arm G)

EXPERIMENTAL

Participants will be administered an IV infusion of cobolimab followed by dostarlimab

Drug: Dostarlimab; Drug: Cobolimab

Interventions

GSK6097608 DRUG

GSK6097608 will be administered as an IV infusion.

Participants receiving GSK6097608 monotherapy (Arm A); Participants receiving GSK6097608 plus dostarlimab (Arm B); Participants receiving dostarlimab plus belrestotug plus GSK6097608 (Arm F)

Dostarlimab DRUG

Dostarlimab will be administered as an IV infusion.

Participants receiving GSK6097608 plus dostarlimab (Arm B); Participants receiving dostarlimab monotherapy (Arm D); Participants receiving dostarlimab plus belrestotug (Arm E); Participants receiving dostarlimab plus belrestotug plus GSK6097608 (Arm F); Participants receiving dostarlimab plus cobolimab (Arm G)

Cobolimab DRUG

Cobolimab will be administered as an IV infusion.

Participants receiving dostarlimab plus cobolimab (Arm G)

Belrestotug DRUG

Belrestotug will be administered as an IV infusion.

Also known as: GSK4428859A, EOS884448

Participants receiving dostarlimab plus belrestotug (Arm E); Participants receiving dostarlimab plus belrestotug plus GSK6097608 (Arm F)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead
• 23andMe, Inc.: collaborator
• iTeos Therapeutics: collaborator

Study Sites (11)

GSK Investigational Site

Los Angeles, California, 90025, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02215, United States

Location

GSK Investigational Site

Dallas, Texas, 75230, United States

Location

GSK Investigational Site

Houston, Texas, 77030-4009, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 1Z5, Canada

Location

GSK Investigational Site

Chiba, 277-8577, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Seoul, 03080, South Korea

Location

GSK Investigational Site

Seoul, 06351, South Korea

Location

MeSH Terms

Conditions

Neoplasms

Interventions

dostarlimab

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will receive treatment in different dose escalation arms of the study.

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: June 24, 2020
• Study Start: June 25, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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
• 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

Locations

CA (2); KR (2); JP (2); US (5)