A First Time in Human (FTIH) Study of GSK3745417 Administered to Participants With Advanced Solid Tumors
Purpose
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.
Condition
- Neoplasms
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- In Part 1A, escalating doses of GSK3745417 will be evaluated and in Part 2A, escalating doses of GSK3745417 in combination with dostarlimab will be evaluated as guided by the Bayesian Logistic Regression Model (BLRM).
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
- Masking Description
- This will be an Open-label study.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1A: Participants receiving GSK3745417, Dose-escalation Cohort |
|
|
|
Experimental Part 2A: Participants receiving GSK3745417 + dostarlimab, Dose escalation Cohort |
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Recruiting Locations
More Details
- NCT ID
- NCT03843359
- Status
- Active, not recruiting
- Sponsor
- GlaxoSmithKline