A First Time in Human (FTIH) Study of GSK3745417 Administered to Participants With Advanced Solid Tumors
- Registration Number
- NCT03843359
- Lead Sponsor
- GlaxoSmithKline
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 97
- 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.
-
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:
- Stimulator of Interferon Genes (STING) agonist at any time.
- Anticancer therapy or investigational therapy or used an investigational device within 28 days or 5 half-lives of the drug, whichever is shorter.
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2A: Participants receiving GSK3745417 + dostarlimab, Dose escalation Cohort Dostarlimab - Part 1A: Participants receiving GSK3745417, Dose-escalation Cohort GSK3745417 - Part 2A: Participants receiving GSK3745417 + dostarlimab, Dose escalation Cohort GSK3745417 -
- Primary Outcome Measures
Name Time Method Parts 1A and 2A: Number of participants achieving dose-limiting toxicity (DLT) Up to Day 29 Parts 1A and 2A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) by severity Up to 2 years
- Secondary Outcome Measures
Name Time Method Part 1A: GSK3745417 concentrations in plasma following administration of GSK3745417 alone Up to Week 104 Part 2A: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with dostarlimab Up to Week 104 Part 2A: Cmax following administration of GSK3745417 in combination with dostarlimab Up to Week 104 Part 2A: AUC following administration of GSK3745417 in combination with dostarlimab Up to Week 104 Part 1A: Maximum observed concentration (Cmax) following administration of GSK3745417 alone Up to Week 104 Part 1A: Area under the concentration-time curve (AUC) following administration of GSK3745417 alone Up to Week 104 Part 1A: Apparent terminal phase half-life (t1/2) following administration of GSK3745417 alone Up to Week 104 Part 2A: T1/2 following administration of GSK3745417 in combination with dostarlimab Up to Week 104
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Madrid, Spain