Advanced or metastatic squamous cell carcinoma of the esophagus MedDRA version: 21.0 Level: LLT Classification code 10015362 Term: Esophageal cancer System Organ Class: 100000004864
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >=18 years • Participants with advanced or metastatic histologically confirmed esophageal squamous-cell carcinoma (ESCC) • Patients who have previously received 1 line of treatment with either a fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in non-curative intention prior to randomization or patients who received treatment with a fluoropyrimidine-/taxane- and platinum-based regimen in curative intention and had recurrence within 24 weeks after the last dose of the treatment. • Radiologically measurable disease according to Response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Previously irradiated lesions should not be counted as target lesions unless clearly progressed after the radiotherapy • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 • A life expectancy of >=12 weeks • Tissue samples must be provided for analysis of anti–programmed death-1 (PD-L1) tumor positivity. • Adequate cardiovascular function • AEs from any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade =25 grams per liter (g/L), • For participants not receiving therapeutic anticoagulation: prothrombin time (PT) and activated partial thromboplastin time =65 years) yes F.1.3.1 Number of subjects for this age range 88
Exclusion criteria
Exclusion criteria: • Pregnancy, lactation, or breastfeeding • Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab, including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies • Patients with significant malnutrition. Patients whose nutrition has been well controlled for >=28 days prior to randomization may be enrolled • Evidence of complete esophageal obstruction not amenable to treatment • Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent organs (aorta or tracheobronchial tree). Patients with manageable fistula may be included at the Investigator's discretion • Symptomatic central nervous system (CNS) metastases • Spinal cord compression not definitively treated with surgery and/or radiation or without evidence that disease has been clinically stable for >=14 days prior to randomization • Active or history of carcinomatous meningitis/leptomeningeal disease • Asymptomatic CNS primary tumors or metastases if they have requirement for steroids or enzyme inducing anticonvulsants in the last 28 days prior to randomization • Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry • Patients with an active second malignancy • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, known autoimmune diseases or immune deficiency, or other diseases with ongoing fibrosis (such as scleroderma, pulmonary fibrosis, emphysema, neurofibromatosis, palmar/plantar fibromatosis, etc.). • Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent • Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization • Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to randomization • Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease. • Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications • Dementia or altered mental status that would prohibit informed consent • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (expected to occur once monthly or more frequently). • Active or history of autoimmune disease or immune deficiency • Positive human immunodeficiency virus (HIV) test at screening • Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core antibody (HBcAb) test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To evaluate the safety and tolerability of RO7121661 and RO7247669 compared with nivolumab •To evaluate the efficacy of RO7247669 compared with nivolumab based on objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and proportion of participants reporting clinically meaningful improvement in global health status/quality of life, emotional functioning, social functioning and dysphagia • To investigate the pharmacokinetics (PK) of RO7247669, and nivolumab • To evaluate the immune response after administration of RO7247669, and nivolumab • To assess treatment-induced pharmacodynamic (PD) changes (PD Biomarkers) in peripheral blood and tumor microenvironment • To assess baseline characteristics in the tumor microenvironment as predictive biomarkers of response;Main Objective: •To evaluate the efficacy of RO7247669 compared with nivolumab based on overall survival;Primary end point(s): 1. Overall survival;Timepoint(s) of evaluation of this end point: 1. From randomization to death (approximately 27 months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Frequency, and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) 2. ORR, defined as the proportion of participants with an objective response (i.e., complete response [CR] or partial response [PR]), according to RECIST v1.1 3. DCR defined as ORR plus stable disease rate (SDR) 4. DoR for participants with ORR, defined as the time from the first occurrence of a documented objective response to disease progression according to RECIST v1.1 or death from any cause, whichever occurs first 5. PFS defined as the time from randomization to the first occurrence of progression as determined according to RECIST v1.1 or death during the treatment period or within 60 days of the last tumor assessment after treatment discontinuation from any cause, whichever occurs first 6. Percentage of participants reporting clinically meaningful improvement in global health status/quality of life, emotional functioning, social functioning and dysphagia as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ)-C30, defined as an improvement of at least 10 points 7. Percentage of participants reporting clinically meaningful improvement in global health status/quality of life, emotional functioning, social functioning and dysphagia as measured by the EORTC-QLQ-IL97, defined as an improvement of at least 10 points 8. Percentage of participants reporting clinically meaningful improvement in global health status/quality of life, emotional functioning, social functioning and dysphagia as measured by the EORTC-QLQ-OES-18, defined as an improvement of at least 10 points 9. Serum concentrations of RO7121661 10. Serum concentrations of RO7247669 11. Serum concentrations of nivolumab 12. Incidence and titer of anti-drug antibodies (ADAs) against RO7121661 during the study relative to the prevalence | — |
Countries
Belgium, Czechia, Czech Republic, Denmark, France, Germany, Hungary, Italy, Korea, Republic of, Netherlands, Poland, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed