Clinical trial NCT06431594: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Participants With Advanced Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumors
Neoplasms
Keywords: Solid Tumors
GSK5733584
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-05-28
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to assess the safety and tolerability of GSK5733584. The study will also see how the levels of GSK5733584 change over time at different dose amount.


Eligibility criteria: Inclusion Criteria:

* Males or females aged 18 years or older (≥18 years).
* Participants with pathologically confirmed advanced solid tumor (who have failed or are intolerant to standard of care).
* PROC cohort

  1. Histologically documented, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer.
  2. Must have received or are intolerant to 1 but no more than 3 lines of prior systemic therapy.
  3. Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy.
  4. Must have had prior bevacizumab if the participant was considered a candidate for this regimen and the regimen is locally available.
  5. Participants with known Folate receptor-α (FR-α) expressing tumors must have received mirvetuximab soravtasine if the participants was considered a candidate for this regimen and the regimen is locally available.
  6. Participants with known Breast cancer susceptibility gene (BRCA) mutated tumors should have received a Poly adenosine diphosphate-ribose polymerase (PARP) inhibitor if the participant was considered a candidate for this regimen and the regimen is locally available.
  7. Maintenance therapy will be considered part of the preceding line of therapy (ie, not counted independently).
* Endometrial cancer cohort

  1. Histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer.
  2. Must have received or are intolerant to 1 but no more than 2 lines of prior systemic therapy.
  3. Must have had prior platinum and PD(L)-1 inhibitor (in same regimen or in separate regimens), if considered a candidate for this regimen and the regimen is locally available.
  4. Maintenance therapy will be considered part of the preceding line of therapy (ie, not counted independently
  5. All epithelial histologies are permitted including carcinosarcoma.
* Participants have at least one target lesion as assessed per the RECIST 1.1
* Tumor tissue from a newly obtained biopsy or archival tumor tissue is required for retrospective detection of B7 homolog 4 (B7-H4) expression by Immunohistochemistry (IHC) in central laboratory and other biomarker analysis. Tissue from a newly obtained biopsy is preferred. If a newly obtained biopsy is not feasible, archival tumor tissue within 2 years prior to the first dose of study drug is acceptable.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 2 and no deterioration within 2 weeks before the first dose.
* Have a life expectancy of at least 12 weeks.

Exclusion Criteria:

* Have received any of B7-H4-targeted therapies.
* Have received any of cytotoxic chemotherapy drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs within 28 days prior to the first dose of study drug; or need to continue these drugs during the study.
* Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.
* Presence of pleural/abdominal effusion/ascites requiring clinical intervention; presence of pericardial effusion
* Major surgery within 4 weeks prior to the first dose of study treatment.
* Evidence of brain metastasis unless asymptomatic.
* Has inadequate bone marrow reserve or hepatic/renal functions.
* Mean Fridericia-corrected QT interval (QTcF) \> 470 millisecond (msec) on resting ECG.
* Evidence of current clinically significant arrhythmias or ECG abnormalities
* Risk factors of prolonged QTc or arrhythmia events,
* Left ventricular ejection fraction (LVEF) \< 50%.
* Have severe, uncontrolled or active cardiovascular disorders, serious or poorly controlled hypertension, clinically significant bleeding symptoms or serious arteriovenous thromboembolic events
* Any evidence of current Interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or pneumonitis requiring high-dose systemic glucocorticoids.
* Have received prior therapy with topoisomerase inhibitors or topoisomerase inhibitor Antibody-drug conjugate (ADCs)
* PROC

  1. Primary platinum refractory not permitted.
  2. Non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma not permitted.
* Endometrial cancer a. Mesenchymal tumors of the uterus (uterine sarcomas) not permitted.

Primary outcomes:
measure: Part 1: Number of participants with dose limiting toxicity (DLT)
timeFrame: Up to 21 days
measure: Part 2: Confirmed Objective Response Rate (ORR)
timeFrame: Up to approximately 28 months
Secondary outcomes:
measure: Part 1 and 2: Maximum observed concentration (Cmax) of GSK5733584 and its components: conjugated antibody, total antibody, and small molecule toxin
timeFrame: Up to approximately 31 months
measure: Part 1 and 2: Time to reach Cmax (Tmax) of GSK5733584 and its components: conjugated antibody, total antibody, and small molecule toxin
timeFrame: Up to approximately 31 months
measure: Part 1 and 2: Area under the concentration-time curve (AUC) of GSK5733584 and its components: conjugated antibody, total antibody, and small molecule toxin
timeFrame: Up to approximately 31 months
measure: Part 1: Confirmed Objective Response Rate (ORR)
timeFrame: Up to approximately 31 months
measure: Part 1 and 2: Duration of response (DoR)
timeFrame: Up to approximately 31 months
measure: Part 1 and 2: Progression-free survival (PFS)
timeFrame: Up to approximately 31 months
measure: Part 1 and 2:Number of participants with treatment-emergent Anti-drug antibodies (ADA)/ Neutralizing antibody (NAb)
timeFrame: Up to approximately 31 months
measure: Part 1 and 2: Titers of ADA to GSK5733584
timeFrame: Up to approximately 31 months
measure: Part 1 and 2: Number of participants with Adverse Events (AEs), and Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: Up to approximately 31 months
measure: Part 1 and 2: Change from baseline in body temperature (degree Celsius)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in respiratory rate (breaths per minute)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in pulse rate (beats per minute)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in blood pressure [millimetres of mercury (mmHg)]
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in weight [kilogram (kg)]
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in white blood cell count (cells per microliter)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in hemoglobin (grams per deciliter)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from Baseline in Platelet count (cells per microliter)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from Baseline in Red Blood Cell Count (RBC) (million cells per microliter)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from Baseline in haematocrit (Proportion of red blood cells in blood)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from Baseline in Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from Baseline in Glucose (fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium Direct Bilirubin and Total Bilirubin (milligrams per decilitre)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from Baseline in AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in Total Protein and Albumin (Grams per deciliter)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in Amylase and Lipase (Units per liter)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in Creatinine clearance (milliliter per minute)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in Prothrombin Time (PT), Partial thromboplastin time (PTT) or Activated Partial Thromboplastin Time (aPTT) (seconds)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in liver panel parameter: International Normalized Ratio (INR)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in routine urine tests: Leukocyte esterase
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in routine urine tests: Occult blood (10^9 Cells Per Liter)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in routine urine tests: potential of hydrogen (pH) value
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in routine urine tests: Protein and bilirubin (Grams Per Liter)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change From Baseline in routine urine tests: Specific Gravity (Ratio)
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in CA-125 tumor marker among ovarian cancer participants [units per milliliter (U/mL)]
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in Thyroid stimulating hormone (TSH) [microunits per milliliter (µU/mL)]
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in free thyroxine (T4) [nanograms per deciliter (ng/dL)]
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in Electrocardiogram (ECG) readings [milliseconds (msec)]
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in Left ventricular ejection fraction (LVEF) [Percentage]
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 1 and 2: Change from baseline in Eastern Cooperative Oncology Group Performance Scale (ECOG PS) score
timeFrame: Baseline (Day -1) and up to approximately 31 months
measure: Part 2: Overall Survival (OS)
timeFrame: Up to approximately 31 months
Other outcomes:
Locations:
city: Lake Mary
country: United States
facility: GSK Investigational Site
state: Florida
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: West Valley City
country: United States
facility: GSK Investigational Site
state: Utah
city: Blacktown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Macquarie University
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Lyon Cedex 08
country: France
facility: GSK Investigational Site
city: Rozzano MI
country: Italy
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Pozuelo De AlarcOn Madr
country: Spain
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
References: