Trial Review

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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
Date last updated
9/08/2024

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
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.
Trial website
https://clinicaltrials.gov/study/NCT03843359
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



Summary Results

For IPD and results data, please see 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]