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

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03843359
• Other study ID #: 208850
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 12, 2019
• Est. completion date: April 5, 2024

Study information

• Verified date: February 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 97
• Est. completion date: April 5, 2024
• Est. primary completion date: April 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• GSK3745417
GSK3745417 will be administered.
• Dostarlimab
Dostarlimab will be administered.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Melbourne	Victoria
Canada	GSK Investigational Site	Toronto	Ontario
France	GSK Investigational Site	Bordeaux Cedex
France	GSK Investigational Site	Villejuif cedex
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Seoul
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Amsterdam
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
United States	GSK Investigational Site	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Japan,  Korea, Republic of,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts 1A and 2A: Number of participants achieving dose-limiting toxicity (DLT)		Up to Day 29
Primary	Parts 1A and 2A: Number of participants with adverse events (AEs) and serious adverse events (SAEs) by severity		Up to 2 years
Secondary	Part 1A: GSK3745417 concentrations in plasma following administration of GSK3745417 alone		Up to Week 104
Secondary	Part 1A: Maximum observed concentration (Cmax) following administration of GSK3745417 alone		Up to Week 104
Secondary	Part 1A: Area under the concentration-time curve (AUC) following administration of GSK3745417 alone		Up to Week 104
Secondary	Part 1A: Apparent terminal phase half-life (t1/2) following administration of GSK3745417 alone		Up to Week 104
Secondary	Part 2A: GSK3745417 concentrations in plasma following administration of GSK3745417 in combination with dostarlimab		Up to Week 104
Secondary	Part 2A: Cmax following administration of GSK3745417 in combination with dostarlimab		Up to Week 104
Secondary	Part 2A: AUC following administration of GSK3745417 in combination with dostarlimab		Up to Week 104
Secondary	Part 2A: T1/2 following administration of GSK3745417 in combination with dostarlimab		Up to Week 104