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

• ClinicalTrials.gov Identifier: NCT03843359
• Recruitment Status: Active, not recruiting
• First Posted: February 18, 2019
• Last Update Posted: May 31, 2023
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 97 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: April 17, 2024
• Estimated Study Completion Date: August 17, 2024

Arms and Interventions

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.

Outcome Measures

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 ]

Eligibility Criteria

• 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.

Contacts and Locations

Locations

United States, Texas

GSK Investigational Site

Houston, Texas, United States, 77030

Australia, Victoria

GSK Investigational Site

Melbourne, Victoria, Australia, 3000

Canada, Ontario

GSK Investigational Site

Toronto, Ontario, Canada, M5G 1Z9

France

GSK Investigational Site

Bordeaux Cedex, France, 33076

GSK Investigational Site

Villejuif cedex, France, 94805

Japan

GSK Investigational Site

Tokyo, Japan, 104-0045

GSK Investigational Site

Tokyo, Japan, 135-8550

Korea, Republic of

GSK Investigational Site

Seoul, Korea, Republic of, 03080

Netherlands

GSK Investigational Site

Amsterdam, Netherlands, 1066 CX

GSK Investigational Site

Amsterdam, Netherlands, 1081 HV

Spain

GSK Investigational Site

Barcelona, Spain, 08035

GSK Investigational Site

Madrid, Spain, 28040

GSK Investigational Site

Madrid, Spain, 28050

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03843359
• Other Study ID Numbers: 208850
• First Posted: February 18, 2019
• Last Update Posted: May 31, 2023
• Last Verified: May 2023

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

• 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

Additional relevant MeSH terms:

Dostarlimab; Antineoplastic Agents