Comparing 6 approaches for neoplasms

Inclusion

• +For combination dose escalationDose escalationLater groups receive higher amounts than earlier ones, increased step by step.Read more →: participants must have received 3 or fewer prior lines of systemic anticancer therapy in the advanced/metastatic setting
• +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 screeningScreeningThe checks done before joining, to see whether a study fits.Read more →; or evidence of meningeal/brainstem involvement; or evidence of spinal cord compression (detected by radiographic examination, symptomatic or not).
• +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 cohortCohortA group of participants sharing a characteristic, followed together.Read more →, as follows:
• +Participants with advanced/metastatic solid tumors.
• +For monotherapy dose escalation: participants must have progressed on or become intolerant to all available SOCStandard of careThe treatment normally given for a condition outside a study.Read more → therapies.
• +Has at least 1 target lesion per RECIST 1.1, as determined by the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →.
• +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 siteTrial siteA hospital or clinic where a study is actually run.Read more → for central testing.
• +Exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more →
• +Has ongoing adverse reactionAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more →(s) from prior therapy that has(have) not recovered to ≤Grade 1 or to the baselineBaselineYour starting measurements, taken before treatment begins.Read more → status preceding prior therapy.
• +Prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents.
• +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.
• +Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before first dose.