A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Clinical Activity of GSK5764227 in Participants with Advanced Solid Tumors

Cancer Categories

Karmanos Trial ID

NCT ID

Age Group

Scope

Phase

Principal Investigator

Phase 1a dose escalation

Primary Objectives:

To determine the MTD/MAD and evaluate the safety and tolerability of GSK5764227 in participants with advanced solid tumors.

Secondary Objectives:

To evaluate the PK profile of GSK5764227 in participants with advanced solid tumors.
To evaluate the clinical activity of GSK5764227 in participants with advanced solid tumors
To evaluate the immunogenicity of GSK5764227 in participants with advanced solid tumors.To evaluate the immunogenicity of GSK5764227 in participants with advanced solid tumors.

Phase 1b dose expansion

Primary Objectives:

To evaluate the clinical activity of GSK5764227 in participants with ES-SCLC or advanced solid tumors.

Secondary Objectives:

To evaluate the safety and tolerability of GSK5764227 in participants with ES-SCLC or advanced solid tumors
To evaluate additional measures of clinical benefit of GSK5764227 in participants with ES-SCLC or advanced solid tumors.
To evaluate the PK profile of GSK5764227 in participants with ES-SCLC or advanced solid tumors.
To evaluate the immunogenicity of GSK5764227 in participants with ES-SCLC or advanced solid tumors.

Eligibility

Inclusion Criteria:

Male or female participants at least 18 years of age (≥18 years)
Participants with histologically confirmed advanced/metastatic solid tumors, irrespective of mutational status, as defined per study phase and cohort, as follows:

Participants with advanced/metastatic tumors who have progressed on or are intolerant to all available standard of care therapies.
Participants with selected advanced/metastatic solid tumors who have progressed on one or more prior lines of therapy.

Has measurable disease (i.e., at least 1 target lesion) per RECIST v1.1, 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 a life expectancy >12 weeks.
Has adequate organ function. Specimens must be collected within 3 days prior to the start of study intervention administration.
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 (archival tumor tissue or a fresh biopsy) is required unless an exemption is granted by the medical monitor. Tumor tissue is necessary for retrospective detection of B7 homolog 3 protein (B7-H3) expression by Immunohistochemistry (IHC) in central laboratory 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.
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 2 weeks prior to initial dosing; and no imaging evidence of severe edema located around the tumor lesion); or untreated progression due to brain metastasis during or after the last treatment prior to screening; or evidence of meningeal/brainstem metastasis; 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%.

Locations

4100 John R
Detroit, MI 48201
Get Directions

Phone: 1-800-527-6266

31995 Northwestern Hwy
Farmington Hills, MI 48334
Get Directions

Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices