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

Inclusion Criteria:

* 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:

  1. 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.
  2. 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:

1. Is not a woman of childbearing potential (WOCBP), or
2. 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 Criteria:

* 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).