本研究旨在評估 Risvutatug rezetecan（Ris-Rez），亦稱 GSK5764227 的安全性、耐受性、臨床活性及藥物動力學。本研究亦將觀察 Ris-Rez 單獨使用及與其他藥物（如 carboplatin、cisplatin、atezolizumab、pembrolizumab、durvalumab、bevacizumab、cetuximab、tarlatamab、dostarlimab）聯合使用時，其水平在不同劑量下隨時間的變化
適應症：Neoplasms
收案條件
納入條件
- 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:
- 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.
排除條件
- 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
- Participants with evidence of current ILD/non-infectious pneumonitis OR a prior history of ILD/non-infectious pneumonitis requiring high-dose glucocorticoids OR suspected ILD/non-infectious pneumonitis that cannot be ruled out by imaging.
- Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening. Participants with prior history of autoimmune disease must be discussed with the medical monitor. Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary).
- Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
- Has received prior anticancer therapy within 28 days of the first dose of study intervention or having to continue these medications during the study.
收案條件維持 ClinicalTrials.gov 原始英文登錄資料，實際收案資格以研究團隊的正式評估與受試者同意書為準。資料來源：ClinicalTrials.gov，每兩週自動更新，最後同步：2026年10月8日。