- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03843359
A First Time in Human (FTIH) Study of GSK3745417 Administered to Participants With Advanced Solid Tumors
February 8, 2024 updated by: GlaxoSmithKline
A Phase I First Time in Human Open Label Study of GSK3745417 Administered With and Without Anticancer Agents in Participants With Advanced Solid Tumors
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
97
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Victoria
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Melbourne, Victoria, Australia, 3000
- GSK Investigational Site
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Ontario
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Toronto, Ontario, Canada, M5G 1Z9
- GSK Investigational Site
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Bordeaux Cedex, France, 33076
- GSK Investigational Site
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Villejuif cedex, France, 94805
- GSK Investigational Site
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Tokyo, Japan, 104-0045
- GSK Investigational Site
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Tokyo, Japan, 135-8550
- GSK Investigational Site
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Seoul, Korea, Republic of, 03080
- GSK Investigational Site
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Amsterdam, Netherlands, 1081 HV
- GSK Investigational Site
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Amsterdam, Netherlands, 1066 CX
- GSK Investigational Site
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Barcelona, Spain, 08035
- GSK Investigational Site
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Madrid, Spain, 28040
- GSK Investigational Site
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Madrid, Spain, 28050
- GSK Investigational Site
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Texas
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Houston, Texas, United States, 77030
- GSK Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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:
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Part 1A: Participants receiving GSK3745417, Dose-escalation Cohort
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GSK3745417 will be administered.
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Experimental: Part 2A: Participants receiving GSK3745417 + dostarlimab, Dose escalation Cohort
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Dostarlimab will be administered.
GSK3745417 will be administered.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Parts 1A and 2A: Number of participants achieving dose-limiting toxicity (DLT)
Time Frame: Up to Day 29
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Up to Day 29
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Parts 1A and 2A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) by severity
Time Frame: Up to 2 years
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Up to 2 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Part 1A: GSK3745417 concentrations in plasma following administration of GSK3745417 alone
Time Frame: Up to Week 104
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Up to Week 104
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Part 1A: Maximum observed concentration (Cmax) following administration of GSK3745417 alone
Time Frame: Up to Week 104
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Up to Week 104
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Part 1A: Area under the concentration-time curve (AUC) following administration of GSK3745417 alone
Time Frame: Up to Week 104
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Up to Week 104
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Part 1A: Apparent terminal phase half-life (t1/2) following administration of GSK3745417 alone
Time Frame: Up to Week 104
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Up to Week 104
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Part 2A: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with dostarlimab
Time Frame: Up to Week 104
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Up to Week 104
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Part 2A: Cmax following administration of GSK3745417 in combination with dostarlimab
Time Frame: Up to Week 104
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Up to Week 104
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Part 2A: AUC following administration of GSK3745417 in combination with dostarlimab
Time Frame: Up to Week 104
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Up to Week 104
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Part 2A: T1/2 following administration of GSK3745417 in combination with dostarlimab
Time Frame: Up to Week 104
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Up to Week 104
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 12, 2019
Primary Completion (Estimated)
April 5, 2024
Study Completion (Estimated)
April 5, 2024
Study Registration Dates
First Submitted
February 14, 2019
First Submitted That Met QC Criteria
February 14, 2019
First Posted (Actual)
February 18, 2019
Study Record Updates
Last Update Posted (Estimated)
February 9, 2024
Last Update Submitted That Met QC Criteria
February 8, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 208850
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place.
Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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