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)
- Conditions
- MelanomaSkin cancer1004090010035023
- Registration Number
- NL-OMON55317
- Lead Sponsor
- ektar Therapeutics
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
1. Provide written, informed consent to participate in the study and follow the
study procedures. The Investigator takes responsibility for ensuring that all
vulnerable patients are protected and participate voluntarily in an environment
free from coercion or undue influence. (See Section 5.2 for details about
obtaining informed consent for adolescent patients.)
2. Male or female patients age 18 years or older at the time of signing the
informed consent form (ICF) (age 18 years or older where local regulations or
institutional policies do not allow for patients < 18 years of age to
participate).
3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance
status of 0 or 1 (>= 17 years of age)/Lansky Performance Score >= 80% (12 to 16
years of age, inclusive) (for details, see Appendix 3).
4. Histologically confirmed Stage IIIA (LN metastasis > 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 that has
been completely surgically resected within 12 weeks prior to randomization.
Patients with presence of 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. (Please refer to Section 5.2 for details of minimum
documentation requirements and Appendix 2 for AJCC 8th edition definitions of
TNM and staging.)
5. Prior treated central nervous system (CNS) metastases must have magnetic
resonance imaging (MRI) evidence of no recurrence for at least 4 weeks after
treatment, subjects must be off immunosuppressive doses of systemic steroids (>
10 mg/day or equivalent) for at least 14 days prior to study drug
administration and must have returned to neurologic baseline post-operatively.
(The 4-week period of stability is measured after the completion of the
neurologic interventions [i.e., surgery and/or radiation]). (Note:
Leptomeningeal disease is excluded.)
6. In addition to neurosurgery to treat CNS metastases, adjuvant radiation
after the resection of CNS metastasis is allowed. Immunosuppressive doses of
systemic steroids (doses >= 10 mg/day prednisone or equivalent) must be
discontinued at least 14 days before study drug administration.
7. Tumor tissue from biopsy or resected disease must be provided to central
laboratory for PD-L1 status analysis. Must have PD-L1 expression classification
(>= 1%, < 1%, indeterminate, or not evaluable) prior to randomization.
8. Disease-free status documented by a complete physical examination and
imaging studies within 28 days prior to randomization (see Table 1 for details
of required assessments).
9. Demonstrated adequate organ function, as defined below:
a. White blood cells >= 2000/µL
b. Absolute neutrophil count >= 1500/µL (1.5 × 109/L)
c. Hemoglobin >= 9.0 g/dL (90 g/L)
d. Platelet count >= 100 × 109/L
e. Total bilirubin <= 1.5 × upper limit of normal (ULN) (except patients with
Gilbert Syndrome, who must have total bilirubin < 3.0 mg/dL)
f. Alanine aminotransferase (ALT) <= 3 × ULN
g. Aspartate aminotransferase (AST) <= 3 × ULN
h. Serum creatinine <= 1.5 × ULN (133 µmol/L) OR calculated creatini
1. Use of an investigational agent or an investigational device within 28 days
before randomization.
2. Female patients who are pregnant or lactating, who plan to get pregnant, or
who have a positive serum or urine pregnancy test.
3. History of ocular/uveal melanoma or mucosal melanoma.
4. Active, known or suspected autoimmune disease. Patients with Type I diabetes
mellitus, hypothyroidism only requiring hormone replacement, skin disorders
(such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are
permitted to enroll.
5. 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.
6. Prior therapy for melanoma. Exceptions include surgery for the melanoma
lesion(s) and/or adjuvant radiation therapy for CNS lesions at least 28 days
prior to randomization. Patients must have recovered from all Grade >= 2
radiation-related toxicities.
7. Prior therapy with interferon, talimogene laherparepvec (Imylgic®), IL-2
directed therapy, anti-PD-1, anti PD L1, anti PD L2, anti-CD137, or anti-CTLA-4
antibody (including ipilimumab or any other antibody or drug specifically
targeting T cell co stimulation or checkpoint pathways).
8. History of leptomeningeal disease.
9. History of hypersensitivity or allergy to study drug components (for
nivolumab, bempegaldesleukin, or any of their excipients).
10. History of severe hypersensitivity reaction to any monoclonal antibody.
11. Prior malignancy active within the previous 3 years except for locally
curable cancers that have been apparently cured, such as basal or squamous cell
skin cancer or prior melanoma, superficial bladder cancer, or carcinoma in situ
of the prostate, cervix, or breast. Consult with the Medical Monitor about
other potential exceptions.
12. History of allogeneic stem cell transplant; history of solid organ or
tissue transplant that requires systemic use of immune suppressive agents.
13. Prior surgery that required general anesthesia within 28 days before the
first dose of study treatment; surgery requiring local/epidural anesthesia
within 72 hours before first dose.
14. Active infection requiring systemic therapy within 14 days prior to
randomization.
15. History of idiopathic pulmonary fibrosis (including pneumonitis),
drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans,
cryptogenic organizing pneumonia), or evidence of active pneumonitis on
Screening chest CT scan.
16. Any positive test result for hepatitis B virus or hepatitis C virus
indicating presence of virus (e.g., hepatitis B surface antigen [HBsAg,
Australia antigen] positive, or hepatitis C antibody [anti-HCV] positive
[except if HCV-RNA negative]).
17. Any positive test result for immunodeficiency or active human
immunodeficiency virus (HIV 1/2 antibodies).
18. Prolonged Fridericia*s corrected QT interval (QTcF) > 450 ms for men and >
470 ms for women at Screening.
19. Kn
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method