A PHASE Ib/II, OPEN-LABEL, MULTICENTER, RANDOMIZED UMBRELLA STUDY EVALUATING THE EFFICACY AND SAFETY OF MULTIPLE TREATMENT COMBINATIONS IN PATIENTS WITH MELANOMA (MORPHEUS-MELANOMA)

Phase 2

Not yet recruiting

• Conditions: Melanoma; Skin cancer; 10040900

• Registration Number: NL-OMON55920
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2024-04-15

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 30

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 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified