Enapotamab Vedotin (HuMax-AXL-ADC) Safety Study in Patients With Solid Tumors

The DLTs were defined as Grade (G) 4 neutropenia or G4 thrombocytopenia for a minimal duration of 7 days, G3 and G4 febrile neutropenia, >=G3 hemorrhage associated with >=G3 thrombocytopenia, G4 anemia; Stevens Johnson syndrome, toxic epidermal necrolysis, >=G3 cutaneous vasculitis; G3 neuropathy (not improved to G1 within 3 weeks following pausing of dosing) and G4 neuropathy; G3 infusion-related reactions (IRR) that did not resolve to G1 or baseline within 24 hours; G4 IRR or G4 anaphylaxis events; >= G3 diarrhoea and/or vomiting persisting >48 hours or G3 nausea lasting 7 days (both despite optimal medical management); or any >=G3 related non-hematological AEs, which occurred during the Cycle 1 and regarded as medically important as assessed by the Data Monitoring Committee (excluding Grade 3 fatigue or non-hematological laboratory abnormalities as specified in protocol).

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is defined as an AE that meets one of the following criteria: requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, is a congenital anomaly/birth defect, is medically important, results in death, or is life-threatening. In this trial, a TEAE was defined as an AE occurring or worsening between the first dose of enapotamab vedotin and 30 days after the last dose received.

Number of participants with treatment-emergent infusion-related AEs and TEAEs related to enapotamab vedotin is reported.

Number of participants with TEAEs of >= Grade 3 as assessed by NCI-CTCAE v4.03 is reported. The NCI-CTCAE is a descriptive terminology is used for AE reporting. The NCI-CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE, based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death. If a participant reported multiple severity grades for an AE, only the maximum grade was used.

Number of participants with laboratory measurements graded as Grade 3 or 4 by NCI-CTCAE v 4.03 is reported.

The AUC0-inf of conjugated enapotamab vedotin for 1Q3W dose-escalation part is reported. Sample scheduling of the 3Q4W dosing regimen did not allow calculation of the specific outcome measure.

The AUC0-last of conjugated enapotamab vedotin for 1Q3W dose-escalation part is reported. Sample scheduling of the 3Q4W dosing regimen did not allow calculation of the specific outcome measure.

The Cmax of conjugated enapotamab vedotin for dose-escalation part is reported.

The total CL of conjugated enapotamab vedotin in dose-escalation part is reported.

The Tmax of conjugated enapotamab vedotin for dose-escalation part is reported.

The t1/2 of conjugated enapotamab vedotin for dose-escalation part is reported.

The Vss of conjugated enapotamab vedotin for dose-escalation part is reported.

The AUC0-inf of MMAE for 1Q3W dose-escalation part is reported. Sample scheduling of the 3Q4W dosing regimen did not allow calculation of the specific outcome measure.

The AUC0-last of MMAE for 1Q3W dose-escalation part is reported. Sample scheduling of the 3Q4W dosing regimen did not allow calculation of the specific outcome measure.

The Cmax of MMAE for dose-escalation part is reported.

The total CL of MMAE in dose-escalation part is reported.

The Tmax of MMAE for dose-escalation part is reported.

The t1/2 of MMAE for dose-escalation part is reported.

The ADA assessment was performed according to a tiered approach. First samples were screened for an ADA response; positively screened samples were analyzed in a confirmation method. Subsequently confirmed positive samples were analyzed for titre and the presence of neutralizing antibodies. Number of participants with ADA confirmed positive to enapotamab vedotin is reported.

Radiological evaluation based on RECIST v1.1 was performed by the investigator using computed tomography (CT) scans/ magnetic resonance imaging (MRI) scans/ positron emission tomography (PET) scans. The OR was defined as confirmed CR or confirmed PR per RECIST v1.1. The changes in tumor measurements that were confirmed by repeat assessments performed no less than 4 weeks after initial response are called confirmed responses. The CR was defined as disappearance of all target and non-target lesions and all pathological lymph nodes must have decreased to < 10 mm in short axis. The PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions taking as reference the baseline sum of LD.

The best CA-125 response was evaluated in participants with ovarian cancer. A CA-125 partial response was defined as at least a 50% reduction in CA-125 levels in blood from a pretreatment sample. Participants who had a CA-125 partial response and had CA-125 level falls to within the reference range (0-35 units/mL) were classified as CA-125 complete responders. The response was confirmed and maintained for at least 28 days. The best overall response (CA-125 partial response and CA-125 complete response) is reported.

The DoR was defined as the number of months from the first documentation of objective tumor response (CR or PR) to the date of first progressive disease (PD) or death. The OR was defined as confirmed CR or confirmed PR per RECIST v1.1. The changes in tumor measurements that were confirmed by repeat assessments performed no less than 4 weeks after initial response are called confirmed responses. The CR was defined as disappearance of all target and non-target lesions and all pathological lymph nodes must have decreased to < 10 mm in short axis. The PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions taking as reference the baseline sum of LD. The PD was defined as at least 20% increase in the sum of LD of target lesions taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of one or more new target and non-target lesions and/or unequivocal progression of existing non-target lesions.

The PFS was defined as the number of months from the date of first study drug administration to first PD or death. The PD was defined as at least 20% increase in the sum of longest diameters of target lesions taking as reference the smallest sum of the longest diameters recorded since the treatment started or the appearance of one or more new lesions. The PFS was estimated using Kaplan-Meier method.

Overall survival was defined as the number of months from date of first study drug administration to death. The OS was estimated using Kaplan-Meier method.

Change in AXL expression (total humor H-score in membrane or cytoplasm) from Baseline to EOT visit for the expansion part is reported. The H-score captures both the intensity and proportion of AXL positive tumor cells and was defined by the formula: H-score = (1 × % 1+ tumor cells) + (2 × % 2+ tumor cells) + (3 × % 3+ tumor cells); where '1+' indicates weak staining intensity, '2+' indicates medium staining intensity, and '3+' indicates strong staining intensity. The H-score values ranges from 0 to 300. Lower H-scores represent lower AXL expression in the tumor sample, while higher scores represent stronger AXL expression in the tumor samples.