Description:
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.
Title
- Brief Title: Study to Compare Adjuvant Immunotherapy of Bempegaldesleukin Combined With Nivolumab Versus Nivolumab After Complete Resection of Melanoma in Patients at High Risk for Recurrence
- Official Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
20-214-29/CA045-022
- NCT ID:
NCT04410445
Conditions
- Melanoma
- Melanoma Stage III
- Melanoma Stage IV
- Melanoma (Skin)
Interventions
Drug | Synonyms | Arms |
---|
Bempegaldesleukin | NKTR-214, BMS-986321 | Combination of bempegaldesleukin (NKTR-214) + nivolumab |
Nivolumab | Opdivo®, BMS-936558 | Combination of bempegaldesleukin (NKTR-214) + nivolumab |
Purpose
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.
Detailed Description
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Combination of bempegaldesleukin (NKTR-214) + nivolumab | Experimental | Arm A: Participants will receive bempegaldesleukin (NKTR-214) IV in combination with nivolumab every 3 weeks. | - Bempegaldesleukin
- Nivolumab
|
Nivolumab | Active Comparator | Arm B: Participants will receive nivolumab IV alone every 4 weeks. | |
Eligibility Criteria
Inclusion Criteria:
- Male or female patients, age 12 years or older at the time of signing the informed
consent form (age 18 years or older where local regulations, countries, and/or
institutional policies do not allow for patients < 18 years of age (adolescents) to
participate). In regions where adolescents are not allowed to participate in the study
due to age restrictions, enrolled patients must be ≥ 18 years of age.
- Histologically confirmed Stage IIIA (LN metastasis > 1 mm), IIIB/C/D, or IV
(M1a/b/c/d) cutaneous melanoma by AJCC (8th edition) at study entry that has been
completely surgically resected within 12 weeks prior to randomization.
- Tumor tissue available from biopsy or resected disease must be provided to central
laboratory for PD-L1 status analysis. Must have PD-L1 expression classification for
stratification purposes.
- Disease-free status documented by a complete physical examination and imaging studies
within 28 days prior to randomization.
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 14 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 (Imylgic®), 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 12 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | RFS of bempegaldesleukin plus nivolumab versus nivolumab alone by BICR, is defined as the time between date of randomization and date of first recurrence, new primary melanoma, or all-cause death |
Time Frame: | Approximately up to 60 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall Survival (OS) defined as the time between the date of randomization and the date of death due to any cause |
Time Frame: | Approximately up to 83 months |
Safety Issue: | |
Description: | |
Measure: | Distant metastasis-free survival (DMFS) by BICR and by Investigator in patients who have Stage IIIA (LN metastasis > 1 mm) or IIIB/C/D melanoma at study entry. |
Time Frame: | Approximately up to 60 months |
Safety Issue: | |
Description: | To evaluate distant metastasis-free survival (DMFS) by BICR and by Investigator in patients who have Stage IIIA (LN metastasis > 1 mm) or IIIB/C/D melanoma at study entry. Distant Metastasis Free Survival is defined as the time between the date of randomization and the date of first distant metastasis or date of death due to any cause. |
Measure: | Overall safety and tolerability of bempegaldesleukin plus nivolumab will be measured by the incidence of AEs, SAEs, deaths, and laboratory abnormalities using CTCAE Version 5.0 criteria |
Time Frame: | Approximately up to 60 months |
Safety Issue: | |
Description: | |
Measure: | Patient Reported Outcomes will be measured by changes from baseline in scores for the global health/quality of life and physical functioning subscales of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire |
Time Frame: | Approximately up to 60 months |
Safety Issue: | |
Description: | |
Measure: | The predictive strength of PD-L1 expression as a biomarker will be measured by the endpoint RFS by BICR based on PD-L1 expression level |
Time Frame: | Approximately up to 60 months |
Safety Issue: | |
Description: | |
Measure: | RFS by Investigator will be measured similarly to the primary endpoint, but recurrence and new primary melanoma will be decided by the Investigator |
Time Frame: | Approximately up to 60 months |
Safety Issue: | |
Description: | |
Measure: | Time to disease progression after the next line of treatment for study patients following discontinuation of bempegaldesleukin plus nivolumab versus nivolumab |
Time Frame: | Approximately up to 60 months |
Safety Issue: | |
Description: | To evaluate time to disease progression after the next line of treatment for study patients following discontinuation of bempegaldesleukin plus nivolumab versus nivolumab |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Nektar Therapeutics |
Trial Keywords
- CD122-Biased Agonist
- CD122-Biased Cytokine
- IL-2 Receptor Agonist
- NKTR-214
- Bempegaldesleukin
- IL-2
- Immunotherapy
- BEMPEG
- Nivolumab
- Opdivo®
- NIVO
- Adjuvant
- Skin Cancer
- Resectable Melanoma
- High Risk of Recurrence Melanoma
- Post Resection
- Checkpoint Inhibitor
Last Updated
August 26, 2021