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

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GlaxoSmithKline (GSK)

Status and phase

Active, not recruiting
Phase 1

Conditions

Leukemia, Myeloid, Acute

Treatments

Drug: GSK3745417

Study type

Interventional

Funder types

Industry

Identifiers

NCT05424380
209809

Details and patient eligibility

About

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.

Enrollment

18 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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:

  • 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 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).

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

18 participants in 2 patient groups

Part 1: Dose escalation
Experimental group
Description:
Part 1 will evaluate a dosing schedule for a total of 28 days in each cycle. The starting dose for Cycle 1 will be escalated in the next dose escalation cohort until MTD is reached.
Treatment:
Drug: GSK3745417
Part 2: Dose expansion
Experimental group
Description:
Part 2 will evaluate efficacy after an induction phase. The induction phase consists of a treatment regimen at RP2D determined in Part 1.
Treatment:
Drug: GSK3745417

Trial contacts and locations

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Central trial contact

US GSK Clinical Trials Call Center; EU GSK Clinical Trials Call Center

Data sourced from clinicaltrials.gov

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