EMD 525797 in Colorectal and Ovarian Cancer Patients With Liver Metastases

Blood plasma volume and extracellular/extravascular volume was measured using DCE-MRI.

Time frame: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1

Population: The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan.

IAUC 60 was used to give a gross indication of the delivery and uptake of contrast agent within the tumor (indicating the degree of perfusion and endothelial permeability. IAUC60 was measured using DCE-MRI.

Time frame: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1

Population: The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan.

Toxicity was graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. A DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring during the first 4 weeks of treatment (that is, until the beginning of Week 5, with the exception of Grade 3 asymptomatic increase in liver function tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], and alkaline phosphatase \[ALP\]) returning to Baseline within 7 days.), at any dose level, for which a causal relationship to the investigative medicinal product could not be ruled out by the Investigator and/or the Sponsor.

Time frame: Up to Week 4

Population: Dose escalation analysis set included all subjects in the safety analysis set who experienced any DLT during the DLT observation period, regardless of the number of investigational medicinal product (IMP) administrations and subjects who received the IMP at Weeks 1, 3, and 5 for Cohort 1 and at Weeks 1 and 3 for all other cohorts.

Volume transfer coefficient was defined as the volume transfer coefficient of contrast agent across the capillary wall, reflecting endothelial permeability and blood flow. Volumetric transfer coefficient was measured by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI is a noninvasive quantitative method of investigating microvascular structure and function by tracking the pharmacokinetics of injected low molecular weight contrast agents as they pass through tumor vasculature.

Time frame: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1

Population: The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan.

Tumor volume (three-dimensional measurement) and the enhancing fraction of the tumor, which provides a gross measure of the proportion of the tumor that has a measurable level of perfusion, were assessed using DCE-MRI.

Time frame: Screening 1, screening 2, Week 1 Day 2, Week 1 Day 5, and Week 2 Day 1

Population: The DCE-MRI analysis set included all subjects who had at least one valid predose scan and at least one valid postdose (that is, after the infusion) scan.

Tumor response was assessed by the Investigator, based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 criteria. Tumor response was defined as the presence of a best overall response of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions and/or normalization of serum levels of tumor markers. PR: At least a 30 percent decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD of target lesions. The qualification of a CR or of a PR needed a confirmation by a second computed tomography (CT) scan at least 4 weeks after the first scan. Best overall response was derived programmatically as the best response recorded from the first investigation medicinal product administration until disease progression. Clinical benefit was defined as the presence of a best overall response of complete response or partial response or stable disease lasting at least 6 weeks.

Time frame: Up to 4 years

Population: The full analysis set included all subjects who received at least one dose of IMP administration. N signifies the total number of participants evaluable for this outcome measure. Same subjects may be reported in more than one category.

Subjects were defined as abituzumab positive if at least one positive result of antibodies against abituzumab was observed. In all other cases, subjects were defined as abituzumab negative.

Time frame: Day 1 of Weeks 1, 3, 5, 6, 7, 8, and week 11 and end of study (EOS) visit (4 weeks after last dose administration)

Population: The immunogenicity analysis set included all subjects who received at least one dose of study drug administration and provided sufficient data from the antibodies samples. 'N' (number of subjects analyzed) signifies the subjects evaluable for this outcome measure. n signifies the number of subjects evaluable for each time point, respectively.

An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/ significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were the AEs that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Time frame: From the initiation of the trial treatment until 30 days after last administration of trial treatment.

Population: The safety analysis set included all subjects who received at least one dose of IMP administration.

The number of subjects who experienced worse post baseline shift were assessed as per ECOG performance status score recorded during the treatment. The ECOG score is categorized as Grade 0, 1, 2, 3 and 4 where Grade 0=fully active, Grade 1=restricted in physically strenuous activity, Grade 2=unable to carry out any work activities, Grade 3=capable of only limited self-care and Grade 4=completely disabled.

Time frame: Up to 4 weeks after last dose administration

Population: The safety analysis set included all subjects who received at least one dose of IMP administration.

PFS was defined as the time from first study drug intake until radiological progression (based on RECIST Version 1.0) or death due to any cause. Only deaths within 84 days of last tumor assessment are considered. Subjects without event were censored on the date of last tumor assessment. Investigator read was the assessment of all imaging by the treating physician at the local trial site.

Time frame: Time from first study drug intake to disease progression, death or last tumor assessment until end of trial visit (4 weeks after last dose administration)

Population: The safety analysis set included all subjects who received at least one dose of IMP administration.