A Study to Evaluate Safety, Pharmacokinetics, and Efficac... | NCT02004106

ID	Type	Description	Link
2013-003041-41	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1: RO6895882 Single Ascending Dose	Experimental	Participants will receive RO6895882 at ascending doses (\	Drug: RO6895882
Part 2: RO6895882 Dose Escalation Monotherapy	Experimental	Participants in different cohorts will receive RO6895882 at ascending doses as IV infusion qw, q2w or q3w. After completion of Part 2 all participants have the option to receive the recommended RO6895882 dose once defined in Part 2 at the discretion of investigator.	Drug: RO6895882
Part 3: RO6895882 MTD Expansion	Experimental	Participants will receive RO6895882 at MTD determined in Part 2 as IV infusion qw, q2w or q3w.	Drug: RO6895882

Interventions

Name	Type	Description	Arm Group Labels	Other Names
RO6895882	Drug	Participants will receive RO6895882 at different dose levels and schedules defined in respective arms as IV infusion.	Part 1: RO6895882 Single Ascending Dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 2: Percentage of Participants With Dose-Limiting Toxicity (DLT)		Part 2: within 21 days after the highest dose administration
Part 2: MTD of RO6895882		Part 2: within 21 days after the highest dose administration
Percentage of Participants With Adverse Events		Day 1 up to 28 days after last dose of study drug (up to approximately 25 months)
Percentage of Participants With Anti-drug Antibodies (ADAs) Against RO6895882	Part 1: Predose (Hour [Hr] 0). Part 2/3: qw schedule (1 cycle = 1 week): Predose in Cycle 1, 4, 5, 6, thereafter every 2 months; Part 2/3: q2w schedule (1 cycle = 2 weeks): Predose in Cycle 1, 4, 6, thereafter every 8 weeks. Part 2/3: q3w schedule (1 cycle = 3 weeks): Predose in Cycle 1, 2, 3, 4, 6, thereafter every 9 weeks. Additionally at treatment discontinuation or at 28-days after last dose (up to approximately 25 months)	Baseline up to 28-days after last dose (up to approximately 25 months) (please see outcome measure description for detailed time frame)
Area Under the Serum Concentration-Time Curve (AUC) of RO6895882	Predose (Hr 0), 1 hr post start of infusion (SoI), at end of infusion (EoI), 2, 4, 24, 72, 96, 216 hrs post Day 1 dose. Part 2/3: qw schedule (1 cycle = 1 week): Predose, 1 hr post SoI, at EoI, 2, 4 hrs after EoI, 24, 72, 96 hrs postdose in Cycle 1, 5 (include 120 hrs postdose); Predose, 24, 96 hrs postdose in Cycle 2, 3, 4; Predose in any later cycle. Part 2/3: q2w schedule (1 cycle = 2 weeks): Predose, 1 hr post SoI, at EoI, 2, 4, 24, 72, 96, 120, 168, 312 hrs postdose in Cycle 1, 4 (exclude 312 hrs postdose); Predose, 24, 96, 168 hrs postdose in Cycle 2; Predose in all later cycles. Part 2/3: q3w schedule (1 cycle = 3 weeks): Predose, 1 hr post SoI, at EoI, 2, 4, 24, 72, 96, 120, 168, 312, 480 hrs postdose in Cycle 1; Predose, 24, 96, 312 hrs postdose in Cycle 2; Predose, at EoI, 1, 2, 4 hrs post EoI, 24, 72, 96, 120, 168, 312 hrs postdose in Cycle 3; Predose, 24, 72, 120, 312 hrs postdose in Cycle 4; Predose in all later cycles. Maximum infusion length = 2 hrs.

Secondary Outcomes

Measure	Description	Time Frame
Count of Cluster of Differentiation (CD) 4+ Cells Analyzed by Flow Cytometry	Part 1: Predose (Hr 0), at EoI, Day (D) 2. Part 2/3: qw schedule (1 cycle = 1 week): Cycle (C) 1: Predose, at EoI, D2, D5; C2: Predose, at EoI, D2; C3: Predose, at EoI; C4: Predose. Part 2/3: q2w schedule (1 cycle = 2 weeks): C1, C4: Predose, at EoI, D2, D5, C2: Predose, at EoI, D2; C3: Predose, at EoI. Part 2/3: q3w schedule (1 cycle = 3 weeks): C1: Predose, at EoI, Day 2, 5, 14; C3: Predose, at EoI, Day 2, 5; C2, C4: Predose, at EoI, Day 2. Maximum infusion length = 2 hrs.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants with confirmed advanced and/or metastatic solid tumor, with at least one tumor lesion of non-critical location accessible to biopsy who have progressed on the standard of care therapy
Locally confirmed CEA expression in tumor tissue (more than [>] 20 percent (%) of tumor cells staining with at least moderate intensity) or centrally confirmed CEA expression if no archival tumor tissue and fresh biopsy is collected
Radiologically measurable and clinically evaluable disease
Life expectancy of greater than or equal to (>/=) 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade </=1, except alopecia (any grade) and Grade 2 peripheral neuropathy
Adequate hematological, liver, and renal function
Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women </=2 years after menopause
Participants with Gilbert's syndrome will be eligible for the study. A diagnosis of Gilbert's syndrome will be based on the exclusion of other diseases based on the following criteria: (i) unconjugated hyperbilirubinemia noted on several occasions; (ii) no evidence of hemolysis (normal hemoglobin, reticulocyte count, and Lactate dehydrogenase); (iii) normal liver function tests; (iv) absence of other diseases associated with unconjugated hyperbilirubinemia

Exclusion Criteria:

History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases unless they have been previously treated, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before screening
Participants with an active second malignancy (other than non-melanoma skin cancer, or cervical carcinoma in situ). Participants who have a history of malignancy are not considered to have an active malignancy if they have completed therapy and are considered by their treating physician to be at less than (<) 30% risk for relapse
Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
Uncontrolled hypertension (systolic >150 millimeter of mercury [mmHg] and/or diastolic >100 mmHg), unstable angina, congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment
Active or uncontrolled infections
Known infection with human immunodeficiency virus (HIV), seropositive status
Positive test results for chronic hepatitis B infection (defined as positive Hepatitis B surface antigen [HBsAg] serology and/or HBcAb status)
Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
Pregnant or breast-feeding women
Known hypersensitivity to any of the components of RO6895882
Concurrent therapy with any other investigational drug
Regular immunosuppressive therapy (that is, for organ transplantation, chronic rheumatologic disease)
Chronic use of steroids (including inhaled) will not be allowed. Concurrent high doses of systemic corticosteroids. High dose is considered as >20 mg of dexamethasone a day (or equivalent) for >7 consecutive days
Radiotherapy within the last 4 weeks before start of study drug treatment with the exception of limited field palliative radiotherapy for bone pain relief

Facility	Status	City	State	ZIP	Country	Contacts
Memorial Sloan Kettering Cancer Center		New York	New York	10065	United States
Rigshospitalet, Onkologisk Klinik