Phase 1
Completed N=27
A Study of EMD525797 in Solid Tumor Patients in Japan
Source: ClinicalTrials.gov NCT01327313 ↗Enrolled (actual)
27
Serious AEs
14.8%
Results posted
May 2016
Primary outcomePrimary: Number of Subjects With Dose-limiting Toxicities (DLTs) — 0; 0; 0; 0 subjects
Summary
The primary objectives are to assess the safety and tolerability of single and repeated doses of EMD525797, and characterize Pharmacokinetics (PK). The secondary objectives are to investigate the immunogenicity and Progressive disease (PD), and to assess the anti-tumor activity of EMD525797.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects With Dose-limiting Toxicities (DLTs) |
0; 0; 0; 0 | — |
| PRIMARY Maximum Observed Serum Concentration (Cmax): After Single Dose |
73.12; 162.48; 419.26; 683.46 | — |
| PRIMARY Maximum Observed Serum Concentration (Cmax) of EMD 525797:After Multiple Dose |
89.336; 198.728; 680.022; 1170.73 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Single Dose |
7942.6; 21562.3; 67545.6; 95369.6 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Multiple Dose |
10674.2; 37344.9; 159979.5; 242989.3 | — |
| PRIMARY Total Body Clearance (CL) of EMD 525797: After Single Dose |
0.0294; 0.0188; 0.0083; 0.0089 | — |
| PRIMARY Total Body Clearance at Steady State (CLss) of EMD 525797 |
0.0224; 0.0154; 0.0075; 0.0078 | — |
| PRIMARY Apparent Volume of Distribution (Vz): After Single Dose |
3.285; 3.284; 3.506; 3.268 | — |
| PRIMARY Pharmacokinetics of EMD 525797 - Trough Values |
5.73; 44.28; 200.05; 286.11 | — |
| PRIMARY Apparent Volume of Distribution: After Multiple Dose |
3.505; 3.775; 4.224; 4.565 | — |
| SECONDARY Number of Subjects With Overall Tumor Response |
0; 0; 0; 0 | — |
| SECONDARY Number of Subjects With Clinical Benefit |
0; 0; 0; 0 | — |
| SECONDARY Progression-free Survival (PFS) |
1.18; 1.23; 1.31; 1.25 | — |
| SECONDARY Apparent Terminal Half Life (t1/2): After Single Dose |
83.95; 114.45; 298.99; 240.76 | — |
| SECONDARY Apparent Terminal Half Life (t1/2): After Multiple Dose |
119.58; 195.75; 345.92; 448.45 | — |
| SECONDARY Time to Maximum Observed Serum Concentration (Tmax): After Single Dose |
1.033; 1.033; 3.967; 1.067 | — |
| SECONDARY Time to Maximum Observed Serum Concentration (Tmax): After Multiple Dose |
1.042; 3.00; 1.025; 4.000 | — |
| SECONDARY Elimination Rate Constant (λz): After Single Dose |
0.00895; 0.00573; 0.00237; 0.00272 | — |
| SECONDARY Elimination Rate Constant ( λ z): After Multiple Dose |
0.00639; 0.00407; 0.00178; 0.00170 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) After Multiple Doses |
5.64; 44.22; 200.5; 286.11 | — |
| SECONDARY Observed Serum Concentration Immediately Before Next Dosing (Cpre) |
5.73; 44.28; 200.05; 286.11 | — |
| SECONDARY Average Serum Concentration at Steady State (Cav) |
33.23; 96.91; 395.47; 574.09 | — |
| SECONDARY Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Single Dose |
7970.1; 21563.6; 67555.4; 100861.0 | — |
| SECONDARY Area Under the Serum Concentration-time Curve Within One Complete Dosing Interval( AUCtau): After Multiple Dose |
11164.0; 32561.0; 132877.8; 192894.5 | — |
| SECONDARY Volume of Distribution at Steady State (Vss) |
3.584; 4.004; 4.131; 4.392 | — |
| SECONDARY Mean Residency Time (MRT0-inf) |
118.46; 187.29; 408.34; 357.21 | — |
| SECONDARY Mean Residence Time at Steady State (MRTss) |
160.05; 260.73; 548.88; 564.86 | — |
| SECONDARY Percentage Peak-Trough Fluctuation (PTF) |
243.64; 157.93; 118.69; 153.22 | — |
| SECONDARY Accumulation Ratio (Rac) |
1.371; 1.510; 1.967; 1.762 | — |
Eligibility Criteria
Inclusion Criteria
- Age greater than or equal to (>=) 20 years
- Histologically or cytologically proven advanced or metastatic solid tumor
- Evidence of progressive disease after standard chemotherapy or no standard chemotherapy
- Confirmation of availability of formalin-fixed paraffin-embedded (FFPE) tumor block(s) or tissue sections
- Presence of at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 complete tumor assessment to be performed within the 30 days prior to the first EMD525797 administration
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Estimated life expectancy of at least 3 months
- Absolute Neutrophil Count (ANC) >= 1.5 x 10^9 per liter (/Liter)
- Platelets >= 100 x 10^9/Liter
- Haemoglobin >= 9.0 gram per deciliter (g/dL) (without transfusions)
- Total bilirubin less than or equal to ( = 50 milliliter per minute (mL/min)
Other protocol defined inclusion criteria could also apply
Exclusion Criteria
- Previous treatment with anti-integrin therapy
- Radiotherapy to bone lesions, systemic surgery, orthopedic surgery (all within the 4 week prior to treatment with EMD525797), clinically significant unhealed wound, or unrecovered bone fracture
- Chronic doses of oral steroids, defined as >= 10 milligram of prednisone equivalents per day
- Confirmed or clinically suspected brain or leptomeningeal metastases
- Known hypersensitivity to EMD525797 or its excipients
- History of allergic reactions to other monoclonal antibody therapy
- Antibody treatment within the past 8 weeks or chemotherapy within the 4 weeks prior to treatment with EMD525797
- Uncontrolled diabetes
- Uncontrolled hypertension defined as systolic blood pressure >= 160 millimeter of mercury (mmHg) and/or diastolic blood pressure >= 100 millimeter of mercury (mmHg) under resting conditions
- Autoimmune diseases
- Current history of chronic daily acetylsalicylic acid (ASS) therapy (ASS at doses <=100 mg is permitted)
- Bleeding disorders;
- History of thromboembolic events (history of superficial thrombophlebitis is not an exclusion
- Anticoagulants within the past 10 days prior to the first treatment and during treatment period
- Severe peripheral vascular disease or ulceration
- Unstable angina pectoris, or myocardial infarction or other severe heart diseases within the past 6 months before treatment with EMD 525797
- Clinical significant abnormal ECG at screening
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
- Known HIV infection, active or chronic carrier of hepatitis B virus (HBV antigen positive or HBV DNA positive) or hepatitis C virus (HCV antibody positive)
Other protocol defined exclusion criteria could also apply
Data sourced from ClinicalTrials.gov (NCT01327313). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.