A Study to Evaluate Safety, Pharmacokinetics, and Efficacy of RO6895882 in Participants With Advanced and/or Metastatic Solid Tumors

Phase 1CompletedNCT02004106

Hoffmann-La Roche110 enrolled

Overview

This open-label, multi-center, dose-escalation study will evaluate the safety, pharmacokinetics, and therapeutic activity of RO6895882 in participants with Carcinoembryonic Antigen (CEA)-positive solid tumors who have progressed on the standard of care therapy. The study will be conducted in 3 parts. Part 1 will be a single ascending dose study in single participant cohort at low RO6895882 dose (less than or equal to \[\</=\] 6 milligrams \[mg\]). Part 2 will be a dose-escalation study of RO6895882 monotherapy given every week (qw), every 2 weeks (q2w), and possibly every 3 weeks (q3w). Part 3 will be an expansion phase of the qw, q2w, and possibly q3w at maximum tolerated dose (MTD) (as determined in Part 2). Part 3 will only be conducted if the risk/benefit assessment, as evaluated by the Sponsor and the investigators, is in favor of the participants. Participants will be treated until disease progression, unacceptable toxicity or withdrawal from treatment for other reasons or death for a maximum duration of 24 months.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

110

Conditions

Neoplasms

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (10)

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Rigshospitalet, Onkologisk Klinik

København Ø, Denmark

Helsinki University Central Hospital; Dept of Oncology

Helsinki, Finland

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, France

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, Netherlands

VU MEDISCH CENTRUM; Dept. of Medical Oncology

Amsterdam, Netherlands

Clinica Universitaria de Navarra; Servicio de oncología

Pamplona, Navarre, Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Spain

CHUV; Departement d'Oncologie

Lausanne, Switzerland

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, United Kingdom

Outcomes

Primary Outcomes

Part 2: Percentage of Participants With Dose-Limiting Toxicity (DLT)

Time frame: Part 2: within 21 days after the highest dose administration

Part 2: MTD of RO6895882

Time frame: Part 2: within 21 days after the highest dose administration

Percentage of Participants With Adverse Events

Time frame: 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)