Melanoma
Conditions
Interventions
Study Treatments for Cohort 1
1. Nivolumab + ipilimumab (control, CIT combination treatment)
2. RO7247669 (CIT single agent treatment)
3. Atezolizumab + tiragolumab (CIT combination treatment)
4. RO
Sponsors
Hoffmann-La Roche
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Shared Inclusion Criteria for Cohort 1 and Cohort 2 Patients must meet all of the following criteria to qualify for Cohort 1 and Cohort 2: • Signed Informed Consent Form • Age >= 18 years at the time of signing Informed Consent Form • ECOG performance status (PS) of 0 or 1 • Ability to comply with the protocol, in the investigator*s judgment • Availability of a representative tumor specimen that is suitable for biomarker testing via central laboratory Baseline tumor tissue samples will be collected from all patients (except patients in the Cohort 2 safety run-in phase) by biopsy of a metastatic lymph node (Cohort 1) or other metastatic lesion (Cohort 2) at screening. In addition, archival primary tumor tissue will be submitted from all patients if available. In case no archival primary tissue is available (e.g., for patients with unknown primary tumor), enrollment is permitted. For archival tissue, a formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) with sufficient size and tumor content representation, preferably including the invasive margin, or if available at least 16 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report. • Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: - ANC >= 1.5 x 109/L (1500/uL) - Lymphocyte count >= 0.5 x 109 cells/L (500/uL) Borderline machine lymphocyte counts may be confirmed by a manual count. - Platelet count >= 100 x 109/L (100,000/uL) - Hemoglobin >= 90 g/L (9 g/dL) - AST, ALT, and ALP <= 2.5 x ULN with the following exceptions: For Cohort 2, patients with documented liver metastases: AST and ALT <= 5 x ULN. For Cohort 2, patients with documented liver or bone metastasis: ALP <= 5 x ULN. - Total bilirubin <= 1.5 x ULN, with the following exception: Patients with known Gilbert disease: bilirubin level <= 3 x ULN - Creatinine <=1.5 x ULN or creatinine clearance >= 30 mL/min (calculated using the Cockcroft-Gault formula) - Serum albumin >= 25 g/L (2.5 g/dL) - For patients not receiving therapeutic anticoagulation: INR and aPTT <= 1.5 x ULN • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen (i.e., no new thrombosis, thromboembolic event, or bleeding episode within 3 months prior to study treatment start) • Negative HIV test at screening with the following exception: Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/uL, and have an undetectable viral load. Patients without a prior positive HIV test result will undergo an HIV test at screening, unless not permitted per local regulations. • Negative hepatitis B surface antibody (HBsAb) and negative total hepatitis B core antibody (HBcAb) test at screening. If a patient has a negative hepatitis B surface antigen (HBsAg) test and a positive total HBcAb test at screening, a hepatitis B virus (HBV) DNA test must also be performed to rule out active HBV. • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test will be perf
Exclusion criteria
Exclusion criteria: Exclusion Criteria for Cohort 1 and Cohort 2 Patients who meet any of the following criteria will be excluded from study entry: • Mucosal and uveal melanoma Acral lentiginous melanoma is excluded for Cohort 1. For Cohort 2, acral lentiginous melanoma is permitted; however, the proportion of patients should not exceed 20% of response-evaluable patients. • Treatment with investigational therapy within 28 days prior to initiation of study treatment • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN] and interleukin [IL]-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment • Prior allogeneic stem cell or solid organ transplantation • Known immunodeficiency or conditions requiring treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor** agents), or anticipation of need for systemic immunosuppressant medication during study treatment, with the following exceptions: Patients on replacement doses of corticosteroids to manage hypopituitary or adrenal insufficiency are eligible for the study. Patients who received acute, low-dose, systemic immunosuppressant medications, or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study. Patients requiring chronic low-dose systemic corticosteroid treatment (i.e., a maximal dose of corticosteroids <= 10mg/day equivalent prednisone) are eligible. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjo*gren syndrome, Guillain-Barre* syndrome, or multiple sclerosis, with the following exceptions: Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. Patients with controlled Type 1 diabetes mellitus who are on a stable insulin regimen are eligible for the study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: - Rash must cover < 10% of body surface area. - Disease is well controlled at baseline and requires only low-potency topical corticosteroids. - There is no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral cortico
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • pRR (defined as the proportion of patients with pCR, pnCR, and pPR) at time of surgery, as determined by independent pathologic review | — |
Secondary
| Measure | Time frame |
|---|---|
| • pRR (defined as the proportion of patients with pCR, pnCR, and pPR) at time of surgery, as determined by local pathologic assessment • EFS, defined as the time from randomization to any of the following events (whichever occurs first): Disease progression that precludes surgery, as assessed by the investigator according to RECIST v1.1; local, regional or distant disease recurrence; or death from any cause • RFS, defined as the time from surgery to the first documented recurrence of disease or death from any cause • OS, defined as the time from randomization to death from any cause • ORR, defined as the proportion of patients with a CR or PR as determined by the investigator according to RECIST v1.1, prior to surgery Responses will be assessed and determined according to RECIST v1.1 but are not required to be confirmed by later imaging studies. • Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to NCI CTCAE v5.0 CRS severity will also be determined according to the ASTCT CRS Consensus Grading Scale. • Incidence and nature of immune-related adverse events Grade * 3 during the first 12 weeks • Rate and duration of delayed surgery due to treatment-related adverse events • Surgical complication rates according to Clavien Dindo surgical classification after CLND | — |
Countries
Netherlands
Outcome results
None listed