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

• Status: Recruiting
• Trial end date: 2023-02-17
• Target enrollment: 0
• Participant gender: All

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. This study will be used to define the recommended Phase 2 dose (RP2D). The study comprises 3 phases; screening phase (28 days prior to first dose), treatment phase (until disease progression, unacceptable toxicity, death, or withdrawal of consent) and follow-up phase (90 days). Approximately 100 adult participants with locally advanced, recurrent, or metastatic solid tumors will be enrolled.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Collaborator: 23andMe, Inc.

Criteria

Inclusion Criteria:

• Adults 18 years of age or older;

• 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;

• 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 must provide a tumor biopsy during the screening period from a tumor lesion and agree to an additional on-treatment biopsy.

• Measurable disease per RECIST 1.1

• 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.

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.

• 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 corrected for heart rate according to Fridericia's formula as measured by electrocardiogram.

• History of hypersensitivity to monoclonal antibodies. For combination therapy, history of hypersensitivity to dostarlimab or its excipients.

• History or evidence of significant cardiovascular (CV) risk.

• 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.