A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of GSK5733584 for Injection in Participants With Advanced Solid Tumors (BEHOLD-1)

GlaxoSmithKline (GSK)

Status and phase: Enrolling; Phase 1

Conditions: Neoplasms; Solid Tumors

Treatments: Drug: GSK5733584

Study type: Interventional

Funder types: Industry

Identifiers

NCT06431594

2024-513860-25 (Other Identifier)

222730

Details and patient eligibility

About

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.

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

Part 1: Dose Escalation

Experimental group

Description:

Participants with advanced solid tumors who are refractory or intolerant to established standard therapies

Treatment:

Drug: GSK5733584

Part 2: Dose Expansion

Experimental group

Description:

Participants with platinum-resistant ovarian cancer (PROC) and endometrial cancer (EC)

Treatment:

Drug: GSK5733584