Last updated: 03/03/2025 18:30:09

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

GSK study ID
209809
See study documents
Clinicaltrials.gov ID
NCT05424380
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase 1, open label study of intravenous GSK3745417 to evaluate safety, tolerability, pharmacokinetics, 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)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Part 1: Number of participants with Adverse Events (AEs) and number of participants per severity grade of AE in total population

Timeframe: Up to 36 weeks

Part 1: Number of participants with Serious Adverse Events (SAEs) and number of participants per severity grade of SAE in total population

Timeframe: Up to 49 weeks

Part 1: Number of participants with Dose limiting toxicities (DLT) and number of participants per severity grade of DLT

Timeframe: Up to 4 weeks

Part 1: Number of participants with withdrawals due to AEs

Timeframe: Up to 36 weeks

Part 2: Overall response rate (ORR) after the daily dosing induction period of GSK3745417

Timeframe: Up to 12 weeks

Part 2: Number of participants with AEs and number of participants per severity grade of AE in total population during maintenance dosing

Timeframe: Up to 36 weeks

Part 2: Number of participants with SAEs and number of participants per severity grade of SAE in total population during maintenance dosing

Timeframe: Up to 49 weeks

Part 2: Number of participants with DLT and number of participants per severity grade of DLT during maintenance dosing

Timeframe: Up to 4 weeks

Part 2: Number of participants with withdrawals due to AEs during maintenance dosing

Timeframe: Up to 36 weeks

Secondary outcomes:

Part 1: Maximum concentration (Cmax) following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 1: Area under the concentration-time curve AUC(0-t) following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 1: AUC (0-tau) following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 1: AUC(0-infinity) following repeated dose administration of GSK3745417

Timeframe: Up to 36 weeks

Part 1: AUC(0-infinity) following single dose administration of GSK3745417

Timeframe: Up to 36 weeks

Part 1: Terminal phase elimination rate constant (Lambda Z) following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 1: Terminal phase half-life (t1/2) following single dose administration of GSK3745417

Timeframe: Up to 36 weeks

Part 1: Systemic clearance of parent drug (CL) following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 1: Volume of distribution (V) following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 2: Number of participants with AEs, leading to dose modification and dose delays

Timeframe: Up to 36 weeks

Part 2: Number of participants with SAEs and AESIs leading to dose modification and dose delays

Timeframe: Up to 49 weeks

Part 2: Cmax following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 2: AUC(0-t) following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 2: AUC (0-tau) following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 2: AUC(0-infinity) following repeated dose of GSK3745417

Timeframe: Up to 36 weeks

Part 2: AUC(0-infinity) following administration of single dose GSK3745417

Timeframe: Up to 36 weeks

Part 2: Lambda Z following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 2: t1/2 following administration of single dose GSK3745417

Timeframe: Up to 36 weeks

Part 2: CL following administration of GSK3745417

Timeframe: Up to 36 weeks

Part 2: V following administration of GSK3745417

Timeframe: Up to 36 weeks

Interventions:
  • Drug: GSK3745417
    • Enrollment:
    18
    Primary completion date:
    2024-04-03
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Leukemia, Myeloid, Acute
    Product
    GSK3745417
    Collaborators
    Not applicable
    Study date(s)
    September 2022 to March 2024
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 75 Years
    Accepts healthy volunteers
    No
    • 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.
    • 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
    Inclusion and exclusion criteria
    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. 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. b. 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: a. Is not a woman of childbearing potential (WOCBP), or b. 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 location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Madrid, Spain, 28033
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Leipzig, Germany, 04103
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Dresden, Germany, 01307
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Madrid, Spain, 28040
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Meldola FC, Italy, 47014
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Toronto, ON, Canada, M5G 2M9
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Perugia, Italy, 06132
    Status
    Study Complete
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    Location
    GSK Investigational Site
    ROTTERDAM, Netherlands, 3015 GD
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Roma, Italy, 00168
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Valencia, Spain, 46026
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Halle, Germany, 06120
    Status
    Terminated/Withdrawn
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    Study documents

    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Other
    Actual primary completion date
    2024-04-03
    Actual study completion date
    2024-04-03

    Plain language summaries

    Summary of results in plain language
    Available language(s): English, Dutch, German, Italian, Spanish
    Download document(s)

    To view plain language summaries on trialsummaries.com click here.

    Additional information about the trial

    Additional information
    Not applicable
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