Resected Stage IIIA (lymph node metastasis > 1 mm)/B/C/D and IV melanoma with no evidence of disease MedDRA version: 21.1 Level: PT Classification code 10025650 Term: Malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Nektar Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: • Male or female patients, = 12 years of age at the time of signing the informed consent form, except where local regulations, countries, and/or institutional policies do not allow for patients 1 mm [i.e., at least one LN metastasis measuring > 1 mm at greatest diameter]), IIIB/C/D, or IV (M1a/b/c/d) cutaneous melanoma by AJCC (8th edition) at study entry. Patients must be completely surgically resected within 12 weeks prior to randomization. Patients with in-transit or microsatellite disease will be allowed if disease has been completely surgically resected. Patients must have been surgically rendered free of disease with negative surgical margins documented, as applicable. • Tumor tissue available from biopsy or resected disease must be provided to central laboratory for biomarker and PD-L1 status analysis. Must have PD-L1 expression classification (= 1%, =65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: • History of ocular/uveal melanoma or mucosal melanoma. • Active, known or suspected autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. • Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. • Prior therapy for melanoma except surgery for the melanoma lesion(s) and/or adjuvant radiation therapy for central nervous system lesions. • Prior therapy with interferon, talimogene laherparepvec (Imlygic®), interleukin-2 (IL-2) directed therapy, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte-associated protein 4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways). • Prior malignancy active within the previous 3 years except for locally potentially curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. Consult with the Medical Monitor about prior melanoma or other potential exceptions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the efficacy, as measured by RFS (recurrence-free survival) by BICR (blinded independent central review), of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (LN metastasis > 1 mm), Stage IIIB/C/D, or Stage IV (AJCC 8th edition) cutaneous melanoma with NED (no evidence of disease) who are at high risk for recurrence.;Secondary Objective: •Compare the OS of bempegaldesleukin plus nivolumab vs nivolumab in patients with completely resected Stage IIIA (LN metastasis > 1 mm), Stage IIIB/C/D, or Stage IV NED mel •Evaluate DMFS by BICR and by Investigator in patients who have Stage IIIA (LN metastasis > 1 mm) or IIIB/C/D melanoma at study entry •Evaluate time to disease progression after the next line of treatment for patients following discontinuation of bempegaldesleukin plus nivolumab vs nivolumab •Assess the overall safety and tolerability of bempegaldesleukin plus nivolumab vs nivolumab in study patients •Describe changes in PROs as assessed by the GH/QoL and physical functioning subscales of the 30-item EORTC QLQ-C30 •Evaluate the association between PD-L1 expression status and RFS by BICR •Assess the efficacy, measured by RFS by Investigator, of bempegaldesleukin plus nivolumab vs nivolumab in patients with completely resected Stage IIIA (LN metastasis > 1 mm), Stage IIIB/C/D, or Stage IV NED melanoma;Primary end point(s): The primary endpoint is RFS by BICR in the ITT population ;Timepoint(s) of evaluation of this end point: determined based on the disease recurrence date provided by BICR and is defined as the time between the date of randomization and the date of first recurrence, new primary melanoma (by BICR), or all-cause death, whichever occurs first. A log-rank test stratified by Stage and PD-L1 status will be used to compare RFS between the two treatment arms at an overall alpha level of 0.05 (two-sided). A stratified Cox proportional hazards model with trea | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: • overall survival (OS) • DMFS by BICR • distant metastasis-free survival (DMFS) by Investigator • Progression-free survival after the next line of treatment (PFS2) • Overall Safety and Tolerability • patient-reported outcomes (PROs ) • PD-L1 expression as a Predictive Biomarker for RFS • recurrence-free survival(RFS) by Investigator;Timepoint(s) of evaluation of this end point: •time between the date of randomization and the date of death due to any cause •time between the date of randomization and the date of first distant metastasis by BICR or date of death due to any cause •time between the date of randomization and the date of first distant metastasis by Investigator or date of death due to any cause •time from randomization to progression per Investigator after the start of next line of therapy or death •the incidence of AEs, SAEs, deaths, and laboratory abnormalities inthe safety population •changes from baseline in scores for the GH/QoL and physical functioning subscales of the EORTC QLQ-C30 •the RFS by BICR endpoints based on PD-L1 expression level •similar to the primary endpoint, but recurrence and new primary melanoma are decided by Investigator | — |
Countries
Australia, Austria, Czechia, Czech Republic, France, Germany, Greece, Israel, Italy, Netherlands, New Zealand, Poland, Portugal, Romania, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactProject Manager
PPD
Outcome results
None listed