Phase 1 First Time in Human (FTIH), Open Label Study of GSK3745417 Administered to Participants With Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2025-01-20
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to evaluate the safety, tolerability, and preliminary clinical activity and establish a recommended dose of GSK3745417 administered alone (Part 1A) or co-administered (Part 2A) with dostarlimab in participants with refractory/relapsed solid tumors. Both parts will consist of a dose escalation phase.

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

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria:

• Participant must be more than or equal to (>=)18 years of age.

• Participants with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.

• Histological or cytological documentation of an advanced solid tumor.

• Participants must provide a fresh biopsy.

• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

• Adequate organ function per protocol specifications.

• Male or female participants.

• Female participants are eligible to participate if they are not breastfeeding or pregnant (or intend to breastfeed or become pregnant). Women of childbearing potential must use a highly effective method of contraception.

• Capable of giving signed informed consent.

Exclusion Criteria:

• 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 within 28 days before the first dose of study treatment.

• Current unstable liver or biliary disease.

• History of vasculitis at any time prior to study treatment.

• Evidence or history of significant active bleeding or coagulation disorder.

• Active infection requiring systemic treatment, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen or hepatitis C.

• QT duration corrected for heart rate by Fridericia's formula (QTcF) more than (>)450 milliseconds (msec) or QTcF >480 msec for participants with bundle branch block.

• Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.

• Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.

• History or evidence of cardiovascular (CV) risk

• Recent (within the past 6 months) history of symptomatic pericarditis.

• History of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis.

• History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

• Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.

• Prior treatment with the following agents:

1. Stimulator of Interferon Genes (STING) agonist at any time.

2. Anticancer therapy or investigational therapy or used an investigational device within 28 days or 5 half-lives of the drug, whichever is shorter.

3. Checkpoint inhibitors, including Programmed death receptor-1 (PD-1), Programmed death Ligand-1 (PD-L1), PD-L2 and Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors within 28 days.

4. Prior radiation therapy: permissible if at least 1 non-irradiated measurable lesion is available for assessment according to RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented.

• Pregnant and/or breast feeding participants or those who plan to become pregnant and/or breastfeed.

• Receipt of any live vaccine within 30 days of the start of study treatment.

• Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.

• Major surgery less than or equal to (<=)28 days before the first dose of study treatment. Participants must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.

• Participants with signs/symptoms suggestive of Coronavirus Disease-2019 (COVID-19) within 14 days of study entry, or with known exposure to COVID-19 within 14 days prior to study entry.

• Participants are excluded from Part 2A of the study if they have known hypersensitivity to dostarlimab or associated excipients.