Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Melanoma

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Disease Attributes

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Arm A: Participants will receive bempegaldesleukin (NKTR-214) IV in combination with nivolumab every 3 weeks.

Arm B: Participants will receive nivolumab IV alone every 4 weeks.

Bempegaldesleukin

Study Director

The main purpose of this study is to compare the efficacy of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA/B/C/D, or Stage IV cutaneous melanoma who are at high risk for recurrence.

The main purpose of this study is to compare the efficacy, as measured by recurrence-free survival (RFS) by blinded independent central review (BICR), of bempegaldesleukin plus nivolumab versus nivolumab in patients with completely resected Stage IIIA (lymph node \[LN\] metastasis \> 1 mm), Stage IIIB/C/D, or Stage IV (American Joint Committee on Cancer \[AJCC\] 8th edition) cutaneous melanoma with no evidence of disease (NED) who are at high risk for recurrence.

Patients will be randomized in a 1:1 ratio to one of two treatment arms

Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence

A Phase 3, Randomized, Open-label Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence (PIVOT-12)

Recurrence-free Survival (RFS) of bempegaldesleukin plus nivolumab versus nivolumab alone is determined based on the disease recurrence date provided by Blinded Independent Central Review (BICR) and is defined as the time between date of randomization and date of first recurrence (local, regional, or distant metastasis by BICR), new primary melanoma (by BICR), or all-cause death, whichever occurs first.

Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. Patients who do not have a date of death will be censored on the last date for which a patient was known to be alive.

Distant metastasis-free survival (DMFS) by Investigator is defined as the time between the date of randomization and the date of first distant metastasis by Investigator or date of death due to any cause, in patients who have Stage III melanoma at study entry.

To evaluate safety and tolerability of (NKTR-214) 0.006 mg/kg in combination with nivolumab 360 mg IV infusion (or 4.5 mg/kg IV infusion q3w for patients \<40 kg) and nivolumab 480 mg IV infusion (or 6.0 mg/kg IV infusion q4w for patients \< 40 kg). Treatment-emergent adverse event (TEAE) is defined as an AE that was not present prior to treatment with study drug but appeared following treatment or was present at treatment start date but worsened during treatment-emergent period. The treatment-emergent period is defined as the period from the date of the first dose of study drug up to 30 days after the date of the last dose of study drug or the day prior to the initiation of subsequent anticancer treatment, whichever occurs first.

The EORTC QLQ-C30 comprises 30 items (i.e. single questions). 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the global health status/quality of life scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 - 10 points is considered a small change, and a change of 10 - 20 points is considered a moderate change. Due to the study termination, results for the mean change from baseline for GH/QoL and the physical functioning subscale were analyzed at approximately 6 months of treatment.

The predictive strength of Programmed Death-Ligand 1 (PD-L1) expression as a biomarker will be measured by the endpoint RFS by BICR based on PD-L1 expression level.

Recurrence-free Survival by Investigator is defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant metastasis by Investigator), new primary melanoma (by Investigator), or all-cause death, whichever occurs first.

Time to disease progression after the next line of treatment is defined as time from randomization to progression per Investigator after the start of next line of therapy or death, whichever occurs first. Patients who were alive and without progression after the next line of therapy can be censored at last known alive date.

Distant Metastasis-Free Survival (DMFS) by Blinded Independent Central Review (BICR) is defined as the time between the date of randomization and the date of first distant metastasis by BICR or date of death due to any cause, whichever occurs first, in patients who have Stage III melanoma at study entry.

Bristol-Myers Squibb

Nektar Therapeutics

Arm A: Participants will receive bempegaldesleukin (NKTR-214) IV in combination with nivolumab every 3 weeks.

Bempegaldesleukin: Specified dose on specified days

Nivolumab: Specified dose on specified days

Combination of Bempegaldesleukin (NKTR-214) + Nivolumab

Arm B: Participants will receive nivolumab IV alone every 4 weeks.

Nivolumab: Specified dose on specified days

Arm A: bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenous (IV) infusion in combination with nivolumab 360 mg IV infusion (or 4.5 mg/kg IV infusion q3w for patients \<40 kg) were administrated every 3 weeks q3w).

Bempegaldesleukin (NKTR-214) + Nivolumab

Arm B: Nivolumab 480 mg IV infusion (or 6.0 mg/kg IV infusion q4w for patients \< 40 kg) every 4 weeks (q4w).

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Romania

United States

Czechia

United Kingdom

Portugal

Russia

Spain

Greece

New Zealand

Austria

Netherlands

Poland

Italy

Israel

Australia

France

Germany

Region of Enrollment

Measure Description: Eastern Cooperative Oncology Group (ECOG) performance status:

ECOG Performance Status of 0 = Able to carry out all normal activities without restriction ECOG Performance Status of 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature

ECOG

The study was terminated early due to the closure of the bempegaldesleukin clinical development program due to lack of enhanced efficacy being observed in combination with nivolumab therapy over nivolumab monotherapy for metastatic melanoma. As a consequence, no aggregate blinded independent central review data were collected; no comparative analyses between bempegaldesleukin + nivolumab arm vs nivolumab arm were conducted for this efficacy endpoint.

Recurrence-free Survival (RFS) by Blinded Independent Central Review (BICR) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone.

For this outcome measure, the results were not estimable due to insufficient number of events. The study was terminated early due to the closure of the bempegaldesleukin clinical program due to lack of enhanced efficacy being observed in combination with nivolumab therapy over nivolumab monotherapy for metastatic melanoma. As a consequence, no comparative analyses between bempegaldesleukin + nivolumab arm vs nivolumab arm were conducted for this efficacy endpoint.

Overall Survival (OS) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone

Participants include only patients who have Stage III melanoma at study entry. The results were not estimable due to insufficient number of events. The study was terminated early due to the closure of the bempegaldesleukin clinical development program due to lack of enhanced efficacy being observed in combination with nivolumab therapy over nivolumab monotherapy for metastatic melanoma.

Distant Metastasis-Free Survival (DMFS) by Investigator in Patients Who Are Stage III at Study Entry.

Patients who had a TEAE

Patients who had a Serious TEAE

Patients who had a TEAE of Grade 3 or higher

Patients who had a TEAE Leading to Death

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Global Health Status/QoL at Baseline

Global Health Status/QoL at 6 Months

Global Health Status/QoL Changes at 6 Months from Baseline

Physical Functioning Subscale at Baseline

Physical Functioning Subscale at 6 Months

Physical Functioning Subscale Changes at 6 Months from Baseline

Changes at 6 Months of Treatment From Baseline in Scores for the Global Health/Quality of Life (GH/QoL) and Physical Functioning Subscales of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire

Programmed Death-Ligand 1 (PD-L1) Expression as a Predictive Biomarker for Recurrence-free Survival (RFS)

Recurrence-free Survival (RFS) by Investigator of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone.

The study was terminated early due to the closure of the bempegaldesleukin clinical development program due to lack of enhanced efficacy being observed in combination with nivolumab therapy over nivolumab monotherapy for metastatic melanoma. As a consequence, no data were collected for this efficacy endpoint.

Time to Disease Progression After the Next Line of Treatment for Study Patients Following Discontinuation of Bempegaldesleukin Plus Nivolumab Versus Nivolumab

The study was terminated early due to the closure of the bempegaldesleukin clinical development program due to lack of enhanced efficacy being observed in combination with nivolumab therapy over nivolumab monotherapy for metastatic melanoma. As a consequence, no blinded independent central review data were collected; no comparative analyses between bempegaldesleukin + nivolumab arm vs nivolumab arm were conducted for this efficacy endpoint.

Spots Global Cancer Trial Database for high risk of recurrence melanoma