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

NCT03843359 | Active Not Recruiting Phase 1 Results FDA Drug

• 1 other identifier: 208850
• Study Type: interventional
• Target: 97
• Locations: 8 countries
• Sites: 13

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

Keywords

GSK3745417; Dostarlimab; Anti-Programmed death receptor-1 (PD-1); Monoclonal antibody; Solid tumor; First time in human; Stimulator of Interferon Genes; STING

Outcome Measures

Primary Outcomes (7)

• Part 1A: Number of Participants Achieving Dose-limiting Toxicity (DLT) Following Administration of GSK3745417 Alone (Q1W)

  AE is DLT if deemed clinically relevant,attributed to study intervention \& met DLT criteria:CytokineReleaseSyndrome (CRS) (Grade(G) 3/4);Liver Toxicity: ALT≥3xULN + bilirubin≥2xULN/INR\>1.5, ALT≥5x ULN+≥2x baseline with liver,metastases/tumor infiltration or HCC;G≥3 non-hematologic exceptions: Transient lab abnormalities, CRS≤G2,Controlled diarrhea,Resolving nausea/vomiting,Alopecia,G3 fatigue\<7 days,G3 headache resolving in 24 hrs;G≥3 immune-related toxicity unresolved in 8 days despite therapy and G≥3 infusion reactions included;Other toxicities: G≥2 uveitis, Unresolved eye pain/blurred vision in 2 wks,Endocrine toxicity needing hormone replacement,Colitis/diarrhea unresolved for ≥7Days despite steroids,ICANS;Hematologic toxicity includes: Neutropenia(G4 ≥7Days or G3/4 with infection/febrile neutropenia),Thrombocytopenia (G4/G3 with bleeding/transfusion),Anemia (G4/G3 needing transfusion);Other events deemed DLTs by the investigator and GSK Medical Monitor per NCI-CTCAE v5.0

  Up to 21 Days

• Parts 1A: Number of Participants Achieving DLT Following Administration of GSK3745417 Alone (Q3W)

  AE is DLT if deemed clinically relevant,attributed to study intervention \& met DLT criteria:CytokineReleaseSyndrome (CRS) (Grade(G) 3/4);Liver Toxicity: ALT≥3xULN + bilirubin≥2xULN/INR\>1.5, ALT≥5x ULN+≥2x baseline with liver,metastases/tumor infiltration or HCC;G≥3 non-hematologic exceptions: Transient lab abnormalities, CRS≤G2,Controlled diarrhea,Resolving nausea/vomiting,Alopecia,G3 fatigue\<7 days,G3 headache resolving in 24 hrs;G≥3 immune-related toxicity unresolved in 8 days despite therapy and G≥3 infusion reactions included;Other toxicities: G≥2 uveitis, Unresolved eye pain/blurred vision in 2 wks,Endocrine toxicity needing hormone replacement,Colitis/diarrhea unresolved for ≥7Days despite steroids,ICANS;Hematologic toxicity includes: Neutropenia(G4 ≥7Days or G3/4 with infection/febrile neutropenia),Thrombocytopenia (G4/G3 with bleeding/transfusion),Anemia (G4/G3 needing transfusion);Other events deemed DLTs by the investigator and GSK Medical Monitor per NCI-CTCAE v5.0

  Up to 29 Days

• Parts 2A: Number of Participants Achieving DLT Following Administration of GSK3745417 in Combination With Dostarlimab (Q1W)

  AE is DLT if deemed clinically relevant,attributed to study intervention \& met DLT criteria:CytokineReleaseSyndrome (CRS) (Grade(G) 3/4);Liver Toxicity: ALT≥3xULN + bilirubin≥2xULN/INR\>1.5, ALT≥5x ULN+≥2x baseline with liver,metastases/tumor infiltration or HCC;G≥3 non-hematologic exceptions: Transient lab abnormalities, CRS≤G2,Controlled diarrhea,Resolving nausea/vomiting,Alopecia,G3 fatigue\<7 days,G3 headache resolving in 24 hrs;G≥3 immune-related toxicity unresolved in 8 days despite therapy and G≥3 infusion reactions included;Other toxicities: G≥2 uveitis, Unresolved eye pain/blurred vision in 2 wks,Endocrine toxicity needing hormone replacement,Colitis/diarrhea unresolved for ≥7Days despite steroids,ICANS;Hematologic toxicity includes: Neutropenia(G4 ≥7Days or G3/4 with infection/febrile neutropenia),Thrombocytopenia (G4/G3 with bleeding/transfusion),Anemia (G4/G3 needing transfusion);Other events deemed DLTs by the investigator and GSK Medical Monitor per NCI-CTCAE v5.0

  Up to 29 Days

• Parts 2A: Number of Participants Achieving Dose-limiting Toxicity (DLT) Following Administration of GSK3745417 in Combination With Dostarlimab (Q3W)

  AE is DLT if deemed clinically relevant,attributed to study intervention \& met DLT criteria:CytokineReleaseSyndrome (CRS) (Grade(G) 3/4);Liver Toxicity: ALT≥3xULN + bilirubin≥2xULN/INR\>1.5, ALT≥5x ULN+≥2x baseline with liver,metastases/tumor infiltration or HCC;G≥3 non-hematologic exceptions: Transient lab abnormalities, CRS≤G2,Controlled diarrhea,Resolving nausea/vomiting,Alopecia,G3 fatigue\<7 days,G3 headache resolving in 24 hrs;G≥3 immune-related toxicity unresolved in 8 days despite therapy and G≥3 infusion reactions included;Other toxicities: G≥2 uveitis, Unresolved eye pain/blurred vision in 2 wks,Endocrine toxicity needing hormone replacement,Colitis/diarrhea unresolved for ≥7Days despite steroids,ICANS;Hematologic toxicity includes: Neutropenia(G4 ≥7Days or G3/4 with infection/febrile neutropenia),Thrombocytopenia (G4/G3 with bleeding/transfusion),Anemia (G4/G3 needing transfusion);Other events deemed DLTs by the investigator and GSK Medical Monitor per NCI-CTCAE v5.0

  Up to 29 Days

• Parts 1A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) by Severity

  AE is any untoward medical occurrence in clinical investigation participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to National Cancer Institute Common Terminology Criteria for AE (NCI-CTCAE) (version 5.0):G1=Mild,G2=Moderate,G3=Severe or medically significant but not immediately life-threatening,G4=Life-threatening consequences,G5=Death related AE.

  Up to approximately 62 weeks

• Parts 2A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) by Severity

  AE is any untoward medical occurrence in clinical investigation participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to NCI-CTCAE v5.0: G1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE.

  Up to approximately 93 weeks

• Crossover Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) by Severity

  AE is any untoward medical occurrence in clinical investigation participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to NCI-CTCAE v5.0: G1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE.

  Up to 30.3 weeks

Secondary Outcomes (28)

• Part 1A: GSK3745417 Concentrations in Plasma Following Administration of GSK3745417 Alone (Q1W)

  Pre-dose on weeks(W) 1-6,9,10,12,19,55;end of infusion(EOI)+5minute(min) on W 1-6, 9,10,12,19,55;EOI+4 hour(HR)/8 HR on W 1-6, 9, 10, 12, 19;EOI+15min/30min/45min/1HR on W 1-6, 9,12;EOI+24HR on W 1-6, 9,10,12; EOI+2HR on W 1-6,9,10,12,19,55

• Part 1A: Area Under the Concentration-time Curve (AUC0-tau) Following Administration of GSK3745417 Alone (Q1W)

  Week 1 to 6, 9, 10, 12, 19

• Part 1A: Maximum Observed Concentration (Cmax) Following Administration of GSK3745417 Alone (Q1W)

  Week 1 to 6, 9, 10, 12, 19

• Part 1A: Apparent Terminal Phase Half-life (t1/2) Following Administration of GSK3745417 Alone (Q1W)

  Week 1 to 6, 9, 10, 12, 19

• Part 1A: GSK3745417 Concentrations in Plasma Following Administration of GSK3745417 Alone (Q3W)

  Pre-dose on W 1, 4, 7, 10, 13, 16, 19; EOI+5min/ 15min/ 30 min/ 45 min/1HR/ 2HR/ 4HR on W 1, 4, 7, 10, 13, 16, 19; EOI+8HR/ 24HR on W 1, 4, 7, 10, 13, 16

Study Arms (2)

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

EXPERIMENTAL

Drug: GSK3745417

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

EXPERIMENTAL

Drug: GSK3745417; Drug: Dostarlimab

Interventions

GSK3745417 DRUG

GSK3745417 will be administered.

Part 1A: Participants receiving GSK3745417, Dose-escalation Cohort; Part 2A: Participants receiving GSK3745417 + dostarlimab, Dose escalation Cohort

Dostarlimab DRUG

Dostarlimab will be administered.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (13)

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Melbourne, Victoria, 3000, Australia

Location

GSK Investigational Site

Toronto, Ontario, M5G 1Z9, Canada

Location

GSK Investigational Site

Bordeaux, 33076, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Tokyo, 135-8550, Japan

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Amsterdam, 1081 HV, Netherlands

Location

GSK Investigational Site

Seoul, 03080, South Korea

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

MeSH Terms

Conditions

Neoplasms; Bites and Stings

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This will be an Open-label study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 18, 2019
• Study Start: March 12, 2019
• Primary Completion: April 4, 2024
• Study Completion: March 31, 2026
• Last Updated: January 8, 2026
• Results First Posted: January 8, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

CA (1); FR (2); ES (3); AU (1); NL (2); JP (2); KR (1); US (1)