Clinical Trials/NCT06551142

NCT06551142

Recruiting

Phase 1

A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of GSK5764227 as Monotherapy and in Combination in Participants With Advanced Solid Tumors

GlaxoSmithKline1 site in 1 country590 target enrollmentSeptember 30, 2024

ConditionsNeoplasms

InterventionsGSK5764227 Cisplatin Carboplatin Atezolizumab Pembrolizumab Durvalumab Cetuximab Bevacizumab

DrugsGSK5764227 Cisplatin Carboplatin Atezolizumab Pembrolizumab Durvalumab Cetuximab Bevacizumab

Overview

Phase: Phase 1
Intervention: GSK5764227
Conditions: Neoplasms
Sponsor: GlaxoSmithKline
Enrollment: 590
Locations: 1
Primary Endpoint: Phase 1a: Number of participants with Adverse Events (AEs)
Status: Recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

The goal of this study is to assess the safety, tolerability, clinical activity and pharmacokinetics of GSK5764227. The study will also see how the levels of GSK5764227 will change over time at different dose amounts when administered alone and in combination with other medicines like carboplatin, cisplatin, atezolizumab, pembrolizumab, durvalumab, bevacizumab, cetuximab.

Registry

clinicaltrials.gov

Start Date

September 30, 2024

End Date

May 19, 2027

Last Updated

4 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female participants at least 18 years of age (≥18 years)
•Participants with histologically confirmed advanced/metastatic solid tumors, as defined per study phase and cohort, as follows:
•o Phase 1a:
•Participants with advanced/metastatic solid tumors.
•For monotherapy dose escalation: participants must have progressed on or become intolerant to all available SOC therapies.
•For combination dose escalation: participants must have received 3 or fewer prior lines of systemic anticancer therapy in the advanced/metastatic setting
•Has at least 1 target lesion per RECIST 1.1, as determined by the investigator.
•Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.
•Has adequate organ function.
•Where available, participants should provide a formalin fixed and paraffin embedded (FFPE) tumor sample from the most recent biopsy of primary cancer or from a metastatic site for central testing. Tumor tissue is necessary for retrospective detection of B7 homolog 3 protein (B7-H3) expression by Immunohistochemistry (IHC) and other biomarker analysis.

Exclusion Criteria

•Has ongoing adverse reaction(s) from prior therapy that has(have) not recovered to ≤Grade 1 or to the baseline status preceding prior therapy.
•Prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents.
•Primary brain tumor or evidence of brain metastasis (unless meeting the following criteria at the same time: asymptomatic; medically stable for at least 4 weeks prior to initial dosing; no steroid treatment required for at least 4 weeks prior to initial dosing; and no midline shift due to herniation); or untreated progression due to brain metastasis or primary brain tumor during or after the last treatment prior to screening; or evidence of meningeal/brainstem involvement; or evidence of spinal cord compression (detected by radiographic examination, symptomatic or not).
•Any of the following cardiac examination abnormality:
•Has QT interval, corrected for heart rate (QTc) \>450 msec or QTc \>480 msec for participants with bundle branch block.
•Evidence of current clinically significant arrhythmias or ECG abnormalities (e.g., complete left bundle branch block, third-degree atrioventricular \[AV\] block, second-degree AV block, PR interval \>250 msec).
•Risk factors of prolonged QTc or arrhythmia events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death of any direct relative under 40 years old or any concomitant medications that prolong the QT interval.
•Left ventricular ejection fraction (LVEF) \<50%.
•Has severe, uncontrolled or active CV 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 non-infectious pneumonitis requiring high-dose glucocorticoids.
•Has donated blood or blood products in excess of 500 mL (approximately 1 pint) within one month prior to first dose of study treatment.

Arms & Interventions

Phase 1a: Dose escalation-GSK5764227 Monotherapy

Intervention: GSK5764227

Phase 1a- Dose escalation- Combination therapy

Intervention: GSK5764227

Phase 1a- Dose escalation- Combination therapy

Intervention: Cisplatin

Phase 1a- Dose escalation- Combination therapy

Intervention: Carboplatin

Phase 1a- Dose escalation- Combination therapy

Intervention: Atezolizumab

Phase 1a- Dose escalation- Combination therapy

Intervention: Pembrolizumab

Phase 1a- Dose escalation- Combination therapy

Intervention: Durvalumab

Phase 1a- Dose escalation- Combination therapy

Intervention: Cetuximab

Phase 1a- Dose escalation- Combination therapy

Intervention: Bevacizumab

Phase 1b- Dose optimisation/ expansion

Intervention: GSK5764227

Phase 1b- Dose optimisation/ expansion

Intervention: Atezolizumab

Outcomes

Primary Outcomes

Phase 1a: Number of participants with Adverse Events (AEs)

Time Frame: Up to approximately 28 months

Phase 1a: Number of participants with Dose Limiting Toxicities (DLTs)

Time Frame: Up to 21 days

Phase 1a: Number of participants with AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) by severity

Time Frame: Up to approximately 30 months

Phase 1a: Number of participants with AEs leading to dose modifications

Time Frame: Up to approximately 28 months

Phase 1a: Number of participants with changes in vital signs, body weight, laboratory tests, electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status

Time Frame: Up to approximately 28 months

Phase 1b: Confirmed Objective Response Rate (cORR)

Time Frame: Up to approximately 27 months

cORR is defined as the proportion of participants who have confirmed Complete response (CR) or Partial response (PR), assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) criteria or other imaging criteria for defined tumor types.

Secondary Outcomes

Phase 1a and Phase 1b: Maximum concentration (Cmax) of GSK5764227(Up to approximately 28 months)
Phase 1a and Phase 1b: Time to reach maximum concentration (Tmax) of GSK5764227(Up to approximately 28 months)
Phase 1a and Phase 1b: Area under the curve (AUC) of GSK5764227(Up to approximately 28 months)
Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5764227 (conjugated antibody)(Up to approximately 28 months)
Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5764227 (total antibody)(Up to approximately 28 months)
Phase 1a and Phase 1b: Trough concentration (Ctrough) of GSK5757810 (small-molecule toxin)(Up to approximately 28 months)
Phase 1a: Confirmed Objective Response Rate (cORR)(Up to approximately 33 months)
Phase 1a: Disease control rate at 12 weeks (DCR12)(At 12 weeks)
Phase 1b: Disease control rate at 12 weeks (DCR12)(At 12 weeks)
Phase 1a: Duration of Response (DoR)(Up to approximately 33 months)
Phase 1b: Duration of Response (DoR)(Up to approximately 33 months)
Phase 1b: Proportion of Participants with Tumour antigen Decrease From Baseline >=50% response rate(Up to approximately 33 months)
Phase 1a and Phase 1b: Number of participants with Antidrug antibody (ADA) or Neutralizing Antibody (NAb)(Up to approximately 30 months)
Phase 1a and Phase 1b: Titers of ADA against GSK5764227(Up to approximately 30 months)
Phase 1b: Number of participants with AEs, SAEs and AESI by severity(Up to approximately 30 months)
Phase 1b: Number of participants with AEs leading to dose modifications(Up to approximately 27 months)
Phase 1b: Number of participants with changes in vital signs, body weight, laboratory tests, ECG, ECHO and ECOG performance status(Up to approximately 28 months)
Phase 1b: Progression-Free Survival (PFS)(Up to approximately 33 months)