A First Time in Human (FTIH) Study of GSK3745417 Administered to Participants With Advanced Solid Tumors

NCT ID: NCT03843359

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-12
• Study Completion Date: 2026-03-31

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.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

GSK3745417

Intervention Type: DRUG

GSK3745417 will be administered.

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

Group Type: EXPERIMENTAL

GSK3745417

Intervention Type: DRUG

GSK3745417 will be administered.

Dostarlimab

Intervention Type: DRUG

Dostarlimab will be administered.

Interventions

GSK3745417

GSK3745417 will be administered.

Intervention Type: DRUG

Dostarlimab

Dostarlimab will be administered.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Melbourne, Victoria, Australia

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Villejuif, , France

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

Countries

United States; Australia; Canada; France; Japan; Netherlands; South Korea; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

208850

Identifier Type: -

Identifier Source: org_study_id