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

Neoplasms Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04446351
• Other study ID #: 212214
• Status: Recruiting
• Phase: Phase 1
• Start date: June 25, 2020
• Est. completion date: September 3, 2025

Study information

• Verified date: October 2023
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 244
• Est. completion date: September 3, 2025
• Est. primary completion date: September 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• GSK6097608
GSK6097608 will be administered as an IV infusion.
• Dostarlimab
Dostarlimab will be administered as an IV infusion.
• Cobolimab
Cobolimab will be administered as an IV infusion.
• Belrestotug
Belrestotug will be administered as an IV infusion.

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
GlaxoSmithKline	23andMe, Inc., iTeos Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Japan,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose-limiting toxicities (DLTs)		Up to Day 21
Primary	Number of participants with adverse events (AEs) and serious adverse events (SAEs)		Up to 2 years
Secondary	Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings		Up to 2 years
Secondary	Number of participants with dose reductions or delay		Up to 2 years
Secondary	Number of participants withdrawn due to AEs		Up to 2 years
Secondary	Overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1		Up to 2 years
Secondary	Arms D, E, F, G: ORR based on modified Response Evaluation Criteria in Solid Tumors (iRECIST)		Up to 2 years
Secondary	Arms D, E, F, G: Disease Control Rate (DCR) based on RECIST 1.1		Up to 2 years
Secondary	Arms D, E, F, G: DCR based on iRECIST		Up to 2 years
Secondary	Arms D, E, F, G: Time to response (TTR) based on RECIST 1.1		Up to 2 years
Secondary	Arms D, E, F, G: TTR based on iRECIST		Up to 2 years
Secondary	Arms D, E, F, G: Duration of response (DOR) based on RECIST 1.1		Up to 2 years
Secondary	Arms D, E, F, G: DOR based on iRECIST		Up to 2 years
Secondary	Arms D, E, F, G: Progression-free survival (PFS) based on RECIST 1.1		Up to 2 years
Secondary	Arms D, E, F, G: PFS based on iRECIST		Up to 2 years
Secondary	Arms A, B, F: Number of participants with positive anti-drug antibodies (ADAs) against GSK6097608		Up to 2 years
Secondary	Arms A, B, F: Titers of ADAs against GSK6097608		Up to 2 years
Secondary	Arms B, D, E, F, G: Number of participants with positive ADAs against dostarlimab		Up to 2 years
Secondary	Arms B, D, E, F, G: Titers of ADAs against dostarlimab		Up to 2 years
Secondary	Arms E, F: Number of participants with positive ADAs against belrestotug		Up to 2 years
Secondary	Arms E, F: Titers of ADAs against belrestotug		Up to 2 years
Secondary	Arm G: Number of participants with positive ADAs against cobolimab		Up to 2 years
Secondary	Arm G: Titers of ADAs against cobolimab		Up to 2 years
Secondary	Arms A, B, F: Maximum observed concentration (Cmax) for GSK6097608		Up to 2 years
Secondary	Arms A, B, F: Minimum observed concentration (Cmin) for GSK6097608		Up to 2 years
Secondary	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
Secondary	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
Secondary	Arms A, B, F: Apparent terminal phase half-life (t1/2) for GSK6097608		Up to 2 years
Secondary	Arms B, D, E, F, G: Cmax for dostarlimab		Up to 2 years
Secondary	Arms B, D, E, F, G: Cmin for dostarlimab		Up to 2 years
Secondary	Arms B, D, E, F, G: AUC(0-infinity) for dostarlimab		Up to 2 years
Secondary	Arms B, D, E, F, G: AUC(0-t) for dostarlimab		Up to 2 years
Secondary	Arms B, D, E, F, G: t1/2 for dostarlimab		Up to 2 years
Secondary	Arms E, F: Cmax for belrestotug		Up to 2 years
Secondary	Arms E, F: Cmin for belrestotug		Up to 2 years
Secondary	Arms E, F: AUC(0-infinity) for belrestotug		Up to 2 years
Secondary	Arms E, F: AUC(0-t) for belrestotug		Up to 2 years
Secondary	Arms E, F: t1/2 for belrestotug		Up to 2 years
Secondary	Arm G: Cmax for cobolimab		Up to 2 years
Secondary	Arm G: Cmin for cobolimab		Up to 2 years
Secondary	Arm G: AUC(0-infinity) for cobolimab		Up to 2 years
Secondary	Arm G: AUC(0-t) for cobolimab		Up to 2 years
Secondary	Arm G: t1/2 for cobolimab		Up to 2 years