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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04410445




Registration number
NCT04410445
Ethics application status
Date submitted
27/05/2020
Date registered
1/06/2020
Date last updated
21/04/2023

Titles & IDs
Public 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
Scientific 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)
Secondary ID [1] 0 0
20-214-29/CA045-022
Universal Trial Number (UTN)
Trial acronym
PIVOT-12
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Melanoma Stage III 0 0
Melanoma Stage IV 0 0
Melanoma (Skin) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Bempegaldesleukin
Treatment: Other - Nivolumab

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

Active comparator: Nivolumab - Arm B: Participants will receive nivolumab IV alone every 4 weeks.


Treatment: Other: Bempegaldesleukin
Specified dose on specified days

Treatment: Other: Nivolumab
Specified dose on specified days
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrence-free Survival (RFS) by Blinded Independent Central Review (BICR) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone.
Timepoint [1] 0 0
Up to 21 months
Secondary outcome [1] 0 0
Overall Survival (OS) of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone
Timepoint [1] 0 0
Up to 21 months
Secondary outcome [2] 0 0
Distant Metastasis-Free Survival (DMFS) by Investigator in Patients Who Are Stage III at Study Entry.
Timepoint [2] 0 0
Up to 21 months
Secondary outcome [3] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [3] 0 0
Approximately up to 21 months
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
From baseline, up to approximately 6 months
Secondary outcome [5] 0 0
Programmed Death-Ligand 1 (PD-L1) Expression as a Predictive Biomarker for Recurrence-free Survival (RFS)
Timepoint [5] 0 0
Up to 21 months
Secondary outcome [6] 0 0
Recurrence-free Survival (RFS) by Investigator of Bempegaldesleukin Plus Nivolumab Versus Nivolumab Alone.
Timepoint [6] 0 0
Up to 21 months
Secondary outcome [7] 0 0
Time to Disease Progression After the Next Line of Treatment for Study Patients Following Discontinuation of Bempegaldesleukin Plus Nivolumab Versus Nivolumab
Timepoint [7] 0 0
Up to 21 months
Secondary outcome [8] 0 0
Distant Metastasis-Free Survival (DMFS) by Blinded Independent Central Review (BICR) in Patients Who Are Stage III at Study Entry.
Timepoint [8] 0 0
Up to 21 months

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/09/2022
Sample size
Target
Accrual to date
Final
765
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Cairns Hospital - Cairns
Recruitment hospital [3] 0 0
Icon Cancer Care Wesley - Chermside
Recruitment hospital [4] 0 0
Gallipoli Medical Research Foundation - Greenslopes
Recruitment hospital [5] 0 0
Austin Health - Heidelberg
Recruitment hospital [6] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [7] 0 0
Affinity Clinical Research - Nedlands
Recruitment hospital [8] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [9] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [10] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [11] 0 0
Tasman Oncology Research - Southport
Recruitment hospital [12] 0 0
Blacktown Hospital - Westmead
Recruitment hospital [13] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
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4870 - Cairns
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4032 - Chermside
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4120 - Greenslopes
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3084 - Heidelberg
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3004 - Melbourne
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6009 - Nedlands
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2000 - North Sydney
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4215 - Southport
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2145 - Westmead
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4102 - Woolloongabba
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Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Nektar Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04410445
Trial related presentations / publications
Eggermont AM, Ascierto PA, Khushalani NI, Schadendorf D, Boland G, Weber J, Lewis KD, Johnson D, Rivalland G, Khattak A, Majem M, Gogas H, Long GV, Currie SL, Chien D, Tagliaferri MA, Carlino MS, Diab A. PIVOT-12: a phase III study of adjuvant bempegaldesleukin plus nivolumab in resected stage III/IV melanoma at high risk for recurrence. Future Oncol. 2022 Mar;18(8):903-913. doi: 10.2217/fon-2021-1286. Epub 2022 Jan 25.
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Nektar Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04410445