A Study of SEA-CD40 Given With Other Drugs in Cancers

Adverse event (AE):untoward medical occurrence in participant/clinical investigational participant administered medicinal product which doesn't necessarily have causal relationship with treatment. Serious AE (SAE):any AE that at any dose resulted in death, life threatening, required hospitalization/prolongation of hospitalization, disabling/incapacitating, congenital anomaly/birth defects.AEs included SAEs,non-SAEs.TEAEs:newly occurring/worsening after 1st dose of treatment.Treatment related TEAEs:related to treatment;relatedness judged by investigator. TEAEs graded according to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) v4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threating, grade 5=fatal). TESAEs:any TEAE that at any dose suspected to cause death, life-threatening, required hospitalization, disabling/incapacitating, congenital anomaly/birth defect. Treatment related TESAEs:related to treatment; relatedness judged by investigator.

In this outcome measure, number of participants with baseline laboratory chemistry values as per NCI-CTCAE grade (grade 0=within normal limits, grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening) and corresponding changes or shift to the worst CTC grades post baseline were presented. Laboratory parameters evaluated: alanine aminotransferase increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase increased, calcium corrected for albumin, creatinine increased, glomerular filtration rate (GFR) estimated decreased, glucose decreased, lactate dehydrogenase increased, potassium, sodium, total bilirubin increased. Baseline was defined as last non-missing grade before first dose of study treatment and worst post-baseline value defined as worst value post study treatment. Only those categories in which at least 1 participant had data in any reporting group were reported.

In this outcome measure, number of participants with baseline laboratory hematology values as per NCI-CTCAE grade (grade 0= within normal limits, grade 1=mild, grade 2=moderate, grade 3= severe, grade 4= life-threatening) and corresponding changes or shift to the worst CTC grades post baseline were presented. Laboratory parameters evaluated: hemoglobin- decreased and increased, leukocytes- decreased and increased, lymphocytes- decreased and increased, neutrophils decreased, platelets decreased. Baseline was defined as last non-missing grade before first dose of study treatment and worst post-baseline value defined as worst value post study treatment. Only those categories in which at least 1 participant had data in any reporting group were reported.

An AE is defined as any untoward medical occurrence in participant/clinical investigational participant administered medicinal product which doesn't necessarily have causal relationship with treatment. Number of participants with dose interruption (SEA-CD40 treatment being temporarily stopped), dose reduction (SEA-CD40 decrease in dose) and dose discontinuation (SEA-CD40 treatment permanently stopped) due to adverse events were reported in this outcome measure.

DCR is defined as the percentage of participants who achieved a confirmed CR or PR according to RECIST v1.1 as assessed by the investigator or met the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 5 weeks. CR: disappearance of all target, non-target lesions, all lymph nodes must be non-pathological in size (<10 mm short axis), PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters persistence of one or more non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase in lesions to qualify for progressive disease (PD) referring smallest sum diameter, PD: at least 20% increase (including absolute increase of at least 5 mm) in sum of diameters of target lesions, taking reference smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

DOR: time from first documentation of OR (confirmed CR or PR) to first documentation of PD or death due to any cause, whichever occurred first. Per RECIST v1.1- CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: >=30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Participants with no PD and were still on study at time of analysis or were removed from study prior to documentation of PD were censored at last disease assessment documenting absence of PD. Participants who started new anticancer treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment. PD: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must demonstrate absolute increase of 0.5 cm. Appearance of 1 or more new lesions. Kaplan-Meier method was used.

PFS is defined as time from start of study treatment to first documentation of PD by RECIST v1.1 or death due to any cause, whichever occurred first. Participants with no PD and were still on study at time of analysis or who were removed from study prior to documentation of PD were censored at the date of last disease assessment documenting absence of PD. Participants who started new anticancer treatment prior to documentation of PD were censored at date of last disease assessment prior to start of new treatment. PD: At least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included baseline sum if that is the smallest on study). In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. Appearance of one or more new lesions was also considered progression. Kaplan-Meier method was used.

OS is defined as the time from the start of study treatment to date of death due to any cause. In the absence of death, survival time was censored at the last date the participant was known to be alive. Kaplan-Meier method was used for analysis.