Phase 1, open label study of intravenous GSK3745417 to evaluate safety, tolerability, harmacokinetics, pharmacodynamics and determine RP2D and schedule in participants with relapsed or refractory myeloid malignancies including acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS)
- Conditions
- Cancer of the blood and bone marrowAcute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS)10024324
- Registration Number
- NL-OMON51352
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
- Must be >=18 years of age and <=75 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participants with AML/High Risk MDS are eligible for participation in Part 1
and Part 2 if they have:
o A diagnosis of AML, with relapsed or refractory disease and ineligible for or
have exhausted standard therapeutic options.
o Have high-risk or high/very high by IPSS-Revised criteria MDS (restricted to
Part 1) that has relapsed after or been refractory to prior therapy with
hypomethylating agent.
o Adequate organ function as defined in the protocol
- Agree to abide by the gender specific contraceptive requirements.
- 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 <=1
- Concomitant administration of drugs that are sensitive substrates or narrow
therapeutic range substrates for cytochrome p450 (CYP)3A4 enzyme, P-gp, BCRP,
OATP1B1 and OATP1B3 transporter, and moderate to strong inducers and inhibitors
of CYP3A4, P-gp, OATP1B1 and OATP1B3 should be excluded during the study and
for 7 days prior to and following treatment with GSK3745417
- Ongoing drug or alcohol abuse.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part 1:<br /><br>Frequency and severity of Adverse Events (AEs), Serious Adverse Events, (SAEs),<br /><br>Dose Limiting Toxicity (DLT), withdrawals due to AEs<br /><br><br /><br>Part2:<br /><br>Objective response rate (ORR) after the daily dosing *induction* period of<br /><br>GSK3745417<br /><br>Frequency and severity of Adverse Events (AEs), Serious Adverse Events, (SAEs),<br /><br>Dose Limiting Toxicity (DLT), withdrawals due to AEs during *maintenance*<br /><br>dosing</p><br>
- Secondary Outcome Measures
Name Time Method