Unresectable or Metastatic Melanoma MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Sponsors
Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General • Age >= 18 years Type of Participants and Disease Characteristics • Participants must have histologically confirmed unresectable or metastatic melanoma, per the American Joint Committee on Cancer (AJCC) staging system • Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (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 • Participants must have known v-Raf murine sarcoma viral oncogene homolog B1(BRAF) V600 mutation status • Participants must have known programmed death-ligand 1 (PD-L1) status • Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses. • Participants must have at least one non-target tumor lesion accessible to biopsy per clinical judgment of the treating physician and consent undergo mandatory on treatment biopsy Medical Conditions • Adequate cardiovascular, hematological, liver, renal function and laboratory parameters • Adverse events (AEs) from any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: General • Pregnancy, lactation, or breastfeeding • Known hypersensitivity to any of the components of RO7247669 including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies Type of Participants and Disease Characteristics • Participants must not have ocular melanoma Medical Conditions • Symptomatic central nervous system (CNS) metastases. Participants with previously treated brain 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 • Participants with an active second malignancy. Concurrent malignancy exceptions include curatively treated carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal or squamous cell skin cancer, or low grade, early stage localized prostate cancer and any previously treated early-stage non-hematological malignancy that has been in remission for at least two years • 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 • 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, parasitic, or other infection, or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization 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 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, pericardial effusion, or ascites requiring recurrent drainage procedures • 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 at screening. Participants with a positive HBsAg or total HBcAb test followed by a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test at screening are eligible • Positive hepatitis C virus (HCV) antibody test at screening. Participants with a positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) tes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the clinical activity of RO7247669 at 600 mg and 1200 mg every 3 weeks (Q3W) on the basis of progression-free survival (PFS);Secondary Objective: • To evaluate the safety and tolerability of RO7247669 at 600 mg and 1200 mg Q3W • To evaluate the clinical activity of RO7247669 at 600 mg and 1200 mg Q3W on the basis of objective response rate (ORR), disease control rate (DCR) and duration of response (DoR) for participants with objective response • To investigate the pharmacokinetics (PK) of RO7247669 at 600 mg and 1200 mg Q3W • To evaluate the immune response after administration of RO7247669 at 600 mg and 1200 mg Q3W • To evaluate potential effects of anti-drug antibodies (ADAs) • To assess treatment-induced pharmacodynamic changes (PD biomarkers) in peripheral blood and tumor microenvironment;Primary end point(s): 1. PFS defined as the time from randomization to the first occurrence of progression as determined by the Investigator 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;Timepoint(s) of evaluation of this end point: 1. Up to approximately 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Nature, frequency, and severity of AEs graded according to the 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 + stable disease rate (SDR) 4. DoR for participants with objective response, 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. Serum concentrations, PK profiles and parameters for RO7247669 6. Incidence and titer of RO7247669 ADAs during the study relative to the prevalence of ADA at baseline 7. Relationship between ADA status and PK, safety, pharmacodynamics, and efficacy 8. Changes from baseline in the phenotype and activation status of T cell subsets in the peripheral blood (CD4/CD8 HLA-DR+/Ki67+) changes from baseline in the tumor microenvironment (such as CD8 T-cell infiltration) 9. Proliferation (CD8+Ki67+) 10. Changes from baseline in the tumor microenvironment (such as CD8 T cell infiltration, proliferation (CD8+Ki67+));Timepoint(s) of evaluation of this end point: 1-4. Up to approximately 24 months 5. At Days 1, 8, 15 of Cycle 1, Days 1, 5 of Cycle 2, Day 1 of Cycles 3 and 4, Days 1, 8, 15 of Cycle 5 and Day 1 of every other cycle until the end of treatment, at treatment discontinuation 6. At Predose of Cycles 1, 2, 3, 4, 5, 7 and then every 2 cycles until the end of treatment 7. Up to approximately 24 months 8-10. Baseline up to approximately 24 months | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, Denmark, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Russian Federation, Slovakia, Spain, Sweden, Switzerland, Turkey
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed