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

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:
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:

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