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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03843359


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT03843359
Ethics application status
Date submitted
14/02/2019
Date registered
18/02/2019

Titles & IDs
Public title
A First Time in Human (FTIH) Study of GSK3745417 Administered to Participants With Advanced Solid Tumors
Scientific title
A Phase I First Time in Human Open Label Study of GSK3745417 Administered With and Without Anticancer Agents in Participants With Advanced Solid Tumors
Secondary ID [1] 0 0
208850
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK3745417
Treatment: Drugs - Dostarlimab

Experimental: Part 1A: Participants receiving GSK3745417, Dose-escalation Cohort -

Experimental: Part 2A: Participants receiving GSK3745417 + dostarlimab, Dose escalation Cohort -


Treatment: Drugs: GSK3745417
GSK3745417 will be administered.

Treatment: Drugs: Dostarlimab
Dostarlimab will be administered.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parts 1A and 2A: Number of participants achieving dose-limiting toxicity (DLT)
Timepoint [1] 0 0
Up to Day 29
Primary outcome [2] 0 0
Parts 1A and 2A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) by severity
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [1] 0 0
Part 1A: GSK3745417 concentrations in plasma following administration of GSK3745417 alone
Timepoint [1] 0 0
Up to Week 104
Secondary outcome [2] 0 0
Part 1A: Maximum observed concentration (Cmax) following administration of GSK3745417 alone
Timepoint [2] 0 0
Up to Week 104
Secondary outcome [3] 0 0
Part 1A: Area under the concentration-time curve (AUC) following administration of GSK3745417 alone
Timepoint [3] 0 0
Up to Week 104
Secondary outcome [4] 0 0
Part 1A: Apparent terminal phase half-life (t1/2) following administration of GSK3745417 alone
Timepoint [4] 0 0
Up to Week 104
Secondary outcome [5] 0 0
Part 2A: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with dostarlimab
Timepoint [5] 0 0
Up to Week 104
Secondary outcome [6] 0 0
Part 2A: Cmax following administration of GSK3745417 in combination with dostarlimab
Timepoint [6] 0 0
Up to Week 104
Secondary outcome [7] 0 0
Part 2A: AUC following administration of GSK3745417 in combination with dostarlimab
Timepoint [7] 0 0
Up to Week 104
Secondary outcome [8] 0 0
Part 2A: T1/2 following administration of GSK3745417 in combination with dostarlimab
Timepoint [8] 0 0
Up to Week 104

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
Accrual to date
Final
97
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
Canada
State/province [2] 0 0
Toronto
Country [3] 0 0
France
State/province [3] 0 0
Bordeaux
Country [4] 0 0
France
State/province [4] 0 0
Villejuif cedex
Country [5] 0 0
Japan
State/province [5] 0 0
Tokyo
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Seoul
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03843359

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
VIC
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
GlaxoSmithKline
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
Approved
 
Public notes

Contacts
Principal investigator
Title 57 0
A/Prof
Name 57 0
Jayesh Desai
Address 57 0
Peter MacCallum Cancer Centre Melbourne VIC 3000
Country 57 0
Australia
Phone 57 0
Fax 57 0
Email 57 0
Contact person for public queries
Title 58 0
Name 58 0
Address 58 0
Country 58 0
Phone 58 0
Fax 58 0
Email 58 0
[email protected]
Contact person for scientific queries
Title 59 0
Name 59 0
Address 59 0
Country 59 0
Phone 59 0
Fax 59 0
Email 59 0
[email protected]