Status:
TERMINATED
A Phase 1, Open Label Study of Intravenous GSK3745417 to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Determine RP2D & Schedule in Participants With Relapsed or Refractory Myeloid Malignancies Including AML and HR MDS
Lead Sponsor:
GlaxoSmithKline
Conditions:
Leukemia, Myeloid, Acute
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
Brief Summary
This is a Phase 1, open label, two-part study to determine recommended phase 2 dose (RP2D) and schedule of GSK3745417 administration in participants with relapsed/refractory AML or HR-MDS.
Eligibility Criteria
Inclusion
- Participants must be ≥18 years of age and ≤75 years of age at the time of signing the informed consent for dose escalation and \>18 years of age at the time of signing the informed consent for the dose expansion.
- Participants must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
- Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participants with AML/HR MDS are eligible for participation in Part 1 and Part 2 if they have:
- A diagnosis of AML according to the World Health Organization 2016 criteria with relapsed or refractory disease and ineligible for or have exhausted standard therapeutic options.
- Have high-risk or high/very high by Revised International Prognostic Scoring System (IPSS-R) for MDS (restricted to Part 1) that has relapsed after or been refractory to prior therapy with hypomethylating agent.
- Participants with a prior history of stem cell transplant (autologous and/or allogeneic) are allowed if:
- No clinical signs or symptoms of graft versus host disease (other than Grade 1 GVHD (\<25% skin surface affected) and the participant is off all systemic immunosuppression. (Note: topical steroids for G1 skin GVHD are permitted on study)
- Participants must agree to abide by the gender specific contraceptive requirements below:
- Female participants are eligible to participate if they are not either pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP), or
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), The effectiveness of the contraceptive method will be evaluated by the investigator in relationship to the first dose of study treatment.
Exclusion
- Diagnosis of acute promyelocytic leukemia (APML or t(15;17) PML-RARA fusion). Patients with biphenotypic disease are excluded.
- Active central nervous system (CNS) involvement or disorder; and well controlled with ongoing treatment
- Participants with Immediate life-threatening, severe complications of leukemia (sepsis, hemorrhage).
- Participants with extramedullary disease as the sole site of AML
- Participants with active severe or uncontrolled infection,
- Participants with active autoimmune disease that has required systemic disease modifying or immunosuppressive treatment within the last 2 years.
- Participants with concurrent medical condition requiring the use of systemic immunosuppressive treatment within 28 days before the first dose of study treatment.
- Participants with history of vasculitis at any time prior to study treatment.
- Participant with a history of other malignancies less than 2 years prior to study entry,
- Participants with QT interval corrected using Fridericia's formula (QTcF) \>450 millisecond (msec) for male participants, \>470 msec for female participants, or \>480 msec for participants with bundle branch block.
- Participants with recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
- Participants with history or evidence of cardiovascular (CV) risk history of immune myocarditis or pericarditis.
- Participants with prior STING therapy.
- Participants with prior solid organ transplantation.
- Participants with recent prior therapy defined as follows: any non-monoclonal anti-cancer therapy within 14 days or 5 half-lives, whichever is longer, prior to start of study treatment; prior therapy with biological agents (including monoclonal antibodies) within 28 days prior to start of study treatment; any radiotherapy or major surgery within 14 days prior to start of study treatment; currently receiving investigational therapy in a clinical trial
- Participants with immune-related toxicity related to prior treatment that has not resolved to Grade ≤1 (except alopecia, hearing loss or Grade ≤2 neuropathy or endocrinopathy managed with replacement therapy).
Key Trial Info
Start Date :
September 20 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 4 2024
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT05424380
Start Date
September 20 2022
End Date
March 4 2024
Last Update
March 25 2025
Active Locations (10)
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1
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
2
GSK Investigational Site
Dresden, Germany, 01307
3
GSK Investigational Site
Leipzig, Germany, 04103
4
GSK Investigational Site
Meldola FC, Italy, 47014