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Phase 1 First Time in Human (FTIH), Open Label Study of GSK3745417 Administered to Participants With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03843359
Recruitment Status : Recruiting
First Posted : February 18, 2019
Last Update Posted : June 22, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: GSK3745417 Drug: Dostarlimab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
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). Part 1B (monotherapy dose expansion) & Part 2B (combination therapy dose expansion) will be planned upon conclusion of dose escalation parts.
Masking: None (Open Label)
Masking Description: This will be an Open-label study.
Primary Purpose: Treatment
Official 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
Actual Study Start Date : March 12, 2019
Estimated Primary Completion Date : November 18, 2024
Estimated Study Completion Date : May 22, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Dostarlimab

Arm Intervention/treatment
Experimental: Part 1A: Participants receiving GSK3745417, Dose-escalation Cohort Drug: GSK3745417
GSK3745417 will be administered.

Experimental: Part 2A: Participants receiving GSK3745417 + dostarlimab, Dose escalation Cohort Drug: GSK3745417
GSK3745417 will be administered.

Drug: Dostarlimab
Dostarlimab will be administered.




Primary Outcome Measures :
  1. Parts 1A and 2A: Number of participants achieving dose-limiting toxicity (DLT) [ Time Frame: Up to Day 29 ]
  2. Parts 1A and 2A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) by severity [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  1. Part 1A: GSK3745417 concentrations in plasma following administration of GSK3745417 alone [ Time Frame: Up to Week 104 ]
  2. Part 1A: Maximum observed concentration (Cmax) following administration of GSK3745417 alone [ Time Frame: Up to Week 104 ]
  3. Part 1A: Area under the concentration-time curve (AUC) following administration of GSK3745417 alone [ Time Frame: Up to Week 104 ]
  4. Part 1A: Apparent terminal phase half-life (t1/2) following administration of GSK3745417 alone [ Time Frame: Up to Week 104 ]
  5. Part 2A: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with dostarlimab [ Time Frame: Up to Week 104 ]
  6. Part 2A: Cmax following administration of GSK3745417 in combination with dostarlimab [ Time Frame: Up to Week 104 ]
  7. Part 2A: AUC following administration of GSK3745417 in combination with dostarlimab [ Time Frame: Up to Week 104 ]
  8. Part 2A: T1/2 following administration of GSK3745417 in combination with dostarlimab [ Time Frame: Up to Week 104 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03843359


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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United States, Texas
GSK Investigational Site Recruiting
Houston, Texas, United States, 77030
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Funda Meric-Bernstam         
Australia, Victoria
GSK Investigational Site Recruiting
Melbourne, Victoria, Australia, 3000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Jayesh Desai         
Canada, Ontario
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 1Z9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Philippe Bedard         
France
GSK Investigational Site Recruiting
Bordeaux Cedex, France, 33076
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Antoine Italiano         
GSK Investigational Site Recruiting
Villejuif cedex, France, 94805
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Sophie Postel-Vinay         
Korea, Republic of
GSK Investigational Site Recruiting
Seoul, Korea, Republic of, 03080
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Dong-Wan Kim         
Netherlands
GSK Investigational Site Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Neeltje Steeghs         
GSK Investigational Site Recruiting
Amsterdam, Netherlands, 1081 HV
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Catharina W. Menke - van der Houven van Oordt         
Spain
GSK Investigational Site Recruiting
Barcelona, Spain, 08035
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Elena Garralda Cabanas         
GSK Investigational Site Recruiting
Madrid, Spain, 28040
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Victor Moreno García         
GSK Investigational Site Recruiting
Madrid, Spain, 28050
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Emiliano Calvo Aller         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03843359    
Other Study ID Numbers: 208850
First Posted: February 18, 2019    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK3745417
Dostarlimab
Anti-Programmed death receptor-1 (PD-1)
Monoclonal antibody
Solid tumor
First time in human
Stimulator of Interferon Genes
STING