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

Study at a glance

From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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)

ClinicalTrials.gov ID

NCT05424380

Acronym / sponsor ID

209809

Conditions

Leukemia, Myeloid, Acute

Keywords

GSK3745417, Acute myeloid leukemia, AML, high-risk myelodysplastic syndrome, HR-MDS

Phase

Phase 1

Study type

Interventional

Recruitment status

TerminatedReason stopped: The protocol was terminated on the basis of a reprioritization of organizational allocation of resources for clinical research programs.

Enrolment

18 participants (actual)

Lead sponsor

GlaxoSmithKlineIndustry (pharma, biotech, devices)

Study start

20 Sep 2022 (actual)

Primary completion

4 Mar 2024 (actual)

Study completion

4 Mar 2024 (actual)

First posted

21 Jun 2022 (actual)

Results

Posted 25 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Non-randomised

Intervention model

Single group

Masking

None (open label)

Number of arms

2

Who may qualify

Ages

18 to 75 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Part 1: Number of Participants With Treatment-emergent (TE) Adverse Events (AEs) and TE Serious AEs (SAEs)

   Time frame: Up to 11.3 weeks

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. A TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state.

2. Part 1: Number of Participants With TEAEs and TESAEs by Severity Grades

   Time frame: Up to 11.3 weeks

   AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 5.0): Grade(G) 1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE.

3. Part 1: Number of Participants With Dose Limiting Toxicities (DLT)

   Time frame: Up to 28 days

   An AE is considered to be a DLT if it is considered by the investigator to be clinically relevant and attributed (definitely, probably, or possibly) to the study intervention and meets at least 1 of the criteria listed below. Criteria for DLT included Grade(G)3 or 4 Cytokine Release Syndrome (CRS); G3 or 4 tumor lysis syndrome (TLS) that cannot be managed/ is not resolved within 72 hours (h); Liver Toxicity included Alanine aminotransferase (ALT)>=3* upper limit of normal (ULN), plus bilirubin>=2* ULN (>35 percent [%] direct) or plus international normalized ratio (INR)>1.5 (Possible Hy's law); G>=3 non-hematologic toxicity of any duration; G>=3 immune-related toxicity that does not resolve to G<=1 or Baseline within 8 days despite adequate immune suppressive therapy. Any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT.

4. Part 1: Number of Participants With Withdrawals Due to AEs

   Time frame: Up to 11.3 weeks

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

5. Part 2: Objective Response Rate (ORR)

   Time frame: Up to Day 84

   Overall response rate (ORR) defined as the percentage of participants with a complete remission (CR), CR with incomplete platelet recovery (CRp), incomplete count recovery (CRi), or a partial remission (PR) as per response criteria for AML and HR-MDS. CR=The participant must achieve a morphologic leukemia-free state (<= 5% blasts) and have no evidence of extramedullary disease. The participant must be free of all symptoms related to leukemia, have an absolute neutrophil count >= 1*10^9/Liter (L) and platelet count >=100*10^9/L, and be transfusion independent. CRp: Marrow response as per CR but platelet count <100 × 10^9/L. CRi: Marrow response as per CR but platelet count <100*10^9/L or neutrophil count <1*10^9/L. PR=A decrease from Baseline of at least 50% in the number of bone marrow blasts, to between 5% and 25% of the bone marrow aspirate.

6. Part 2: Number of Participants With TEAEs and TESAEs

   Time frame: Up to 49 weeks

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. A TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state.

7. Part 2: Number of Participants With TEAEs and TESAEs by Severity Grades

   Time frame: Up to 49 weeks

   AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment. TEAE is an event that emerges during treatment having been absent pretreatment or worsens relative to the pretreatment state. AEs were graded by the investigator according to NCI-CTCAE (version 5.0): G1=Mild, G2=Moderate, G3=Severe or medically significant but not immediately life-threatening, G4=Life-threatening consequences, G5=Death related AE.

8. Part 2: Number of Participants With Dose Limiting Toxicities (DLT)

   Time frame: Up to 28 days

   An AE is considered to be a DLT if it is considered by the investigator to be clinically relevant and attributed (definitely, probably, or possibly) to the study intervention and meets at least 1 of the criteria listed below. Criteria for DLT included Grade(G)3 or 4 Cytokine Release Syndrome (CRS); G3 or 4 TLS that cannot be managed/ is not resolved within 72 hours (h); Liver Toxicity included ALT>=3*upper limit of normal (ULN), plus bilirubin>=2*ULN (>35% direct) or plus international normalized ratio (INR)>1.5 (Possible Hy's law); G>=3 non-hematologic toxicity of any duration; G>=3 immune-related toxicity that does not resolve to G<=1 or Baseline within 8 days despite adequate immune suppressive therapy. Any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT.

9. Part 2: Number of Participants With Withdrawals Due to AEs

   Time frame: Up to 49 weeks

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

10 sites in 5 countries: see every site and its status.