A Study of EMD525797 in Solid Tumor Patients in Japan

Merck KGaA, Darmstadt, Germany27 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumor

Interventions

EMD525797BIOLOGICAL

Subjects will receive 250 milligram (mg) of EMD525797 intravenously every 2 weeks, until progressive disease (PD), unacceptable toxicity or withdrawal of consent.

EMD525797BIOLOGICAL

Subjects will receive 500 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity or withdrawal of consent.

EMD525797BIOLOGICAL

Subjects will receive 1000 mg of EMD525797 intravenously every 2 weeks, until PD or unacceptable toxicity or withdrawal of consent.

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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 (\<=) 1.5 x upper limit of normal (ULN) * Aspartate transaminase (AST), alanine transaminase (ALT) less than or equal to (\<=) 3 x ULN * In subjects with hepatic metastasis, total bilirubin \<= 3 x ULN, AST and ALT \<= 5 x ULN * Prothrombin time (PT), prothrombin time/international normalized ratio (PT/INR), and activated partial thromboplastin time (APTT) within normal limits * Creatinine clearance \>= 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

Locations (1)

For Recruiting

Locations in, Japan

Outcomes

Primary Outcomes

Number of Subjects With Dose-limiting Toxicities (DLTs)

DLT was defined as any Grade 3 or 4 haematological or non-haematological toxicity occurring at any dose level until the end of Week 4, and suspected to be reasonably related to the investigational medicinal product by the Investigator and/or Sponsor. Toxicities not considered to be DLTs are as follows- Allergic reactions or anaphylaxis; any Grade 3 or 4 out-of-range laboratory values without any clinical correlate, which were reversible within 7 days, unless the Investigator decided this event is clinically significant. For this reason Grade 3 or 4 out-of-range laboratory values must be re-assessed within 7 days. In case the Investigator provides the subject any treatment(s) due to the out-of-range laboratory values, the event was regarded as a DLT.

Time frame: Baseline up to Week 4

Maximum Observed Serum Concentration (Cmax): After Single Dose

Time frame: Pre-dose, hour 1(end of infusion [EOI]), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1

Maximum Observed Serum Concentration (Cmax) of EMD 525797:After Multiple Dose

Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5

Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Single Dose

Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above Lower limit of quantification (LLQ).

Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1

Area Under the Curve From Time Zero to Last Quantifiable Concentration(AUC0-t) of EMD 525797: After Multiple Dose

Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above LLQ.

Time frame: Pre-dose, hour 1 (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 5

Data from ClinicalTrials.gov

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Secondary Outcomes

Number of Subjects With Overall Tumor Response

Overall tumor response was defined as the presence of at least one confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0. Complete response was defined as the disappearance of all target and non-target lesions and normalization of serum levels of tumor markers. PR is at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD.

Time frame: Baseline up to Week 36

Number of Subjects With Clinical Benefit

Clinical benefit was defined as presence of at least one confirmed CR, PR, or stable disease (SD) lasting at least 12 weeks according to RECIST v1.0. Per RECIST v1.0: CR was defined as disappearance of all target and non-target lesions and normalization of serum levels of tumor markers . PR was defined as \>=30% decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions.

Time frame: Baseline up to Week 36

Progression-free Survival (PFS)

PFS time was defined as the time (in months) from the first dosing date to the date of first documentation of disease progression as reported and documented by the Investigator (i.e. radiological progression per RECIST version 1.0) or death for any cause within 12 weeks after last tumor assessment. Subjects without event are censored on the date of last tumor assessment.

Time frame: From first dosing date until disease progression or death, maximum up to Week 36

Apparent Terminal Half Life (t1/2): After Single Dose

Time frame: Pre-dose, end of infusion (EOI), 4, 8, 24, 48, and 96 hours after start of infusion at Week 1

Apparent Terminal Half Life (t1/2): After Multiple Dose