Cancer of the blood and bone marrow
Conditions
Interventions
Intervention
For Part 1, approximately 22 participants will receive dosing in the hospital
on a 5 days on/2 days off schedule for 2 weeks, and then have an additional 2
weeks off dose for observatio
Sponsors
GlaxoSmithKline
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Must be >=18 years of age and
Exclusion criteria
Exclusion criteria: - Diagnosis of acute promyelocytic leukemia Patients with biphenotypic disease are excluded. - Active central nervous system involvement or disorder. - Immediate life-threatening, severe complications of leukemia - Participants with extramedullary disease as the sole site of AML - Active severe or uncontrolled infection, known human immunodeficiency virus infection, or presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test at screening. - Participants with signs/symptoms suggestive of COVID-19 within 14 days of study entry, or with known exposure to COVID-19 within 14 days prior to study entry - 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. - Recent history of allergen desensitization therapy within 4 weeks of starting study treatment. - History or evidence of cardiovascular (CV) risk - Prior STING therapy. - Prior solid organ transplantation. - Recent prior therapy defined as follows: o Any non-monoclonal anti-cancer therapy within 14 days or 5 half-lives, whichever is longer, prior to start of study treatment o Prior therapy with biological agents within 28 days prior to start of study treatment o Any radiotherapy or major surgery within 14 days prior to start of study treatment o Currently receiving investigational therapy in a clinical trial - Receipt of any live vaccine within 30 days of start of study treatment. - Immune-related toxicity related to prior treatment that has not resolved to Grade
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Frequency and severity of Adverse Events (AEs), Serious Adverse Events, (SAEs), Dose Limiting Toxicity (DLT), withdrawals due to AEs Part2: Objective response rate (ORR) after the daily dosing *induction* period of GSK3745417 Frequency and severity of Adverse Events (AEs), Serious Adverse Events, (SAEs), Dose Limiting Toxicity (DLT), withdrawals due to AEs during *maintenance* dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: GSK3745417 concentrations in plasma or PK parameters Part 2: AEs, SAE, AESIs leading to dose modifications or delays GSK3745417 concentrations in plasma or PK parameters Exploratory: Part 1: Objective response rate (ORR) as measured by standard disease specific response criteria. The relationship between GSK3745417 exposure (e.g., concentration, Cmax, or other exposure parameter) and the following safety parameters may be included based on the availability of data and appropriateness: • AEs leading to dose reductions or delays • Change from baseline in safety laboratory parameters • Change from baseline in other safety assessments (such as vital signs, ECG) • Changes in cardiac QT duration corrected for heart rate by Fridericia*s formula (QTcF) and/or other safety parameters in relation to GSK3745417 exposure markers. Association between dose and PD parameters. PD assessment may include apoptotic markers and/or immune activation (e.g., serum cytokines, T cell activation markers, acute phase proteins) in peripheral blood samples and bone marrow. Association between GSK3745417 dose and ORR as measured by standard response criteria. Assessment may include: induction of apoptosis markers, cell killing, and changes in immune activation status based on induction of cytokines, immune profiles and gene signatures in peripheral blood and/or bone marrow. Other biomarkers including genetic analysis (DNA) in blood and/or bone marrow and assessments by immunohistochemistry (IHC) or related technologies Part 2: DoR, if data permit Milestone EFS rate at 6 months AEs leading to dose reductions or delays Change from baseline in safety laboratory parameters Change from baseline in other safety assessments (such as vital signs, ECG) Changes in cardiac QT duration corrected for heart rate by Fridericia*s formula (QTcF) and/or other safety parameters in relation to GSK3745417 exposure markers as appropriate. Data from Part1 and Part 2 may be | — |
Countries
Netherlands
Outcome results
None listed