## Protocol Section
### Identification Module
**NCT ID:** NCT06431594

**Brief Title:** 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

#### Organization Study ID Info
**ID:** 222730
#### Organization
**Class:** INDUSTRY
**Full Name:** GlaxoSmithKline
#### Secondary ID Infos
**Domain:** EU CT Number
**ID:** 2024-513860-25
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2027-01-21

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-22

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-10-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-29

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-28
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-21
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** GlaxoSmithKline

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Solid Tumors

**Keywords:**

- Solid Tumors

- GSK5733584

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** SEQUENTIAL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 240

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: GSK5733584

**Label:** Part 1: Dose Escalation

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: GSK5733584

**Label:** Part 2: Dose Expansion

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Part 1: Dose Escalation

- Part 2: Dose Expansion

**Description:** GSK5733584 will be administered

**Name:** GSK5733584

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Part 1: Number of participants with dose limiting toxicity (DLT)

**Time Frame:** Up to 21 days

**Description:** ORR is defined as the proportion of participants with at least one confirmed Complete Response (CR) or Partial Response (PR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

**Measure:** Part 2: Objective Response Rate (ORR)

**Time Frame:** Up to approximately 28 months

#### Secondary Outcomes

**Measure:** Part 1 and 2: Maximum observed concentration (Cmax) of GSK5733584

**Time Frame:** Up to approximately 31 months

**Measure:** Part 1 and 2: Time to reach Cmax (Tmax) of GSK5733584

**Time Frame:** Up to approximately 31 months

**Measure:** Part 1 and 2: Area under the concentration-time curve (AUC) of GSK5733584

**Time Frame:** Up to approximately 31 months

**Description:** ORR is defined as the proportion of participants with at least one confirmed CR or PR as defined by RECIST 1.1

**Measure:** Part 1: Objective Response Rate (ORR)

**Time Frame:** Up to approximately 31 months

**Description:** DCR is defined as the percentage of subjects whose best overall response is Complete Response (CR), Partial Response (PR) or Stable Disease (SD)

**Measure:** Part 1 and 2: Disease control rate (DCR)

**Time Frame:** Up to approximately 31 months

**Description:** DoR is defined as the time interval between the date of the first documented response (CR or PR) and the date of the first documented disease progression or death due to any cause

**Measure:** Part 1 and 2: Duration of response (DoR)

**Time Frame:** Up to approximately 31 months

**Description:** PFS is defined as the time interval between randomization (or from the first dose of the intervention) and the first documented disease progression or death due to any cause (whichever occurs first).

**Measure:** Part 1 and 2: Progression-free survival (PFS)

**Time Frame:** Up to approximately 31 months

**Measure:** Part 1 and 2:Number of participants with treatment-emergent Anti-drug antibodies (ADA)

**Time Frame:** Up to approximately 31 months

**Measure:** Part 1 and 2: Titers of ADA to GSK5733584

**Time Frame:** Up to approximately 31 months

**Measure:** Part 1 and 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

**Time Frame:** Up to approximately 31 months

**Measure:** Part 1 and 2: Number of participants with clinically significant changes in physical examination

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in body temperature (degree Celsius)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in respiratory rate (breaths per minute)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in pulse rate (beats per minute)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in blood pressure [millimetres of mercury (mmHg)]

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in weight [kilogram (kg)]

**Time Frame:** 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)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in hemoglobin (grams per deciliter)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from Baseline in Platelet count (cells per microliter)

**Time Frame:** 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)

**Time Frame:** 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)

**Time Frame:** 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)

**Time Frame:** 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)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Description:** Aspartate Aminotransferase (AST) / Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase and (SGPT), Alkaline phosphatase (ALP) and Creatinine Phosphokinase (CPK) will be analysed

**Measure:** Part 1 and 2: Change from Baseline in AST/SGOT, ALT/ SGPT, ALP and CPK (International Units per litre)

**Time Frame:** 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)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in Amylase and Lipase (Units per liter)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in Creatinine clearance (milliliter per minute)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in Activated Partial Thromboplastin Time (aPTT), Prothrombin Time (PT) and Thrombin time (seconds)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in fibrinogen (milligrams per deciliter)

**Time Frame:** 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)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Description:** Leukocyte esterase measured as negative or positive

**Measure:** Part 1 and 2: Change from baseline in routine urine tests: Leukocyte esterase

**Time Frame:** 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)

**Time Frame:** 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

**Time Frame:** 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)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change From Baseline in routine urine tests: Specific Gravity (Ratio)

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in CA-125 tumor marker [units per milliliter (U/mL)]

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in Electrocardiogram (ECG) readings [milliseconds (msec)]

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Measure:** Part 1 and 2: Change from baseline in Left ventricular ejection fraction (LVEF) [Percentage]

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Description:** ECOG PS is used for measuring how the disease impacts a patient's daily living abilities. The grades for the scale range from 0 (fully active) to 5 (dead), with increasing severity.

**Measure:** Part 1 and 2: Change from baseline in Eastern Cooperative Oncology Group Performance Scale (ECOG PS) score

**Time Frame:** Baseline (Day -1) and up to approximately 31 months

**Description:** OS is defined as the time interval between the date of randomization (or from the first dose of the investigational product) and the date of death due to any cause

**Measure:** Part 2: Overall Survival (OS)

**Time Frame:** Up to approximately 31 months

### Eligibility Module

**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).
* 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** GSKClinicalSupportHD@gsk.com

**Name:** US GSK Clinical Trials Call Center

**Phone:** 877-379-3718

**Role:** CONTACT

**Contact 2:**

**Email:** GSKClinicalSupportHD@gsk.com

**Name:** EU GSK Clinical Trials Call Center

**Phone:** +44 (0) 20 89904466

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Lake Mary

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Alexander Philipovskiy

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** GSK Investigational Site

**State:** Florida

**Zip:** 32746

**Location 2:**

**City:** Boston

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Sara Bouberhan

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** GSK Investigational Site

**State:** Massachusetts

**Zip:** 02114

**Location 3:**

**City:** Boston

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Antonio Giordano

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** GSK Investigational Site

**State:** Massachusetts

**Zip:** 02215

**Location 4:**

**City:** Detroit

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Ira Winer

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** GSK Investigational Site

**State:** Michigan

**Zip:** 48201

**Location 5:**

**City:** Dallas

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Minal Barve

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** GSK Investigational Site

**State:** Texas

**Zip:** 75230

**Location 6:**

**City:** West Valley City

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** William McKean

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** GSK Investigational Site

**State:** Utah

**Zip:** 84119

**Location 7:**

**City:** Sydney

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Dhanusha Sabanathan

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Australia

**Facility:** GSK Investigational Site

**State:** New South Wales

**Zip:** 2109

**Location 8:**

**City:** Ottawa

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Moira Katherine Rushton-Marovac

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Canada

**Facility:** GSK Investigational Site

**State:** Ontario

**Zip:** K1H 8L6

**Location 9:**

**City:** Toronto

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Philippe Bedard

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Canada

**Facility:** GSK Investigational Site

**State:** Ontario

**Zip:** M5G 2M9

### IPD Sharing Statement Module

**Access Criteria:** Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

**Description:** Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

**IPD Sharing:** YES

**Time Frame:** Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

**URL:** https://www.gsk.com/en-gb/innovation/trials/data-transparency/

## Derived Section

### Condition Browse Module - Meshes

- ID: D000009369

- Term: Neoplasms

### Misc Info Module

- Version Holder: 2024-05-31
