A Multicenter, Double-blind, Placebo-controlled, Adaptive Phase 3 Trial of POL-103A Polyvalent Melanoma Vaccine in Post-resection Melanoma Patients with a High Risk of Recurrence
POL-103A is an investigational melanoma vaccine that contains multiple melanoma-associated antigens that are shed from 3 human melanoma cell lines, admixed with alum as the adjuvant. The presence of multiple antigens is an important element in maximizing the induction of tumor-protective immune responses and reducing a tumor cell’s ability to escape the immune response. The vaccine has been administered (in various forms) to approximately 690 subjects who were treated for up to 5 years at antigen doses of 40 µg per treatment. These subjects were treated without significant toxicity and the results demonstrated preliminary evidence of efficacy. In one study, a double-blind and placebo-controlled trial of a related version of the vaccine (4 melanoma cell lines plus alum) in patients with Stage III melanoma (n=38), the recurrence-free survival of the melanoma vaccine-treated subjects was over twice as long as that of placebo vaccine-treated subjects.
This study will be conducted in two parts. Part A (dose evaluation, number of subjects = 99) is designed to determine the safety profile and immunogenicity of two different doses of POL-103A – 40 µg or 100 µg or vs placebo and to determine the dose to be used in Part B of the study. The decision to proceed to Part B (clinical efficacy evaluation, number of subjects = 960) will be based on evidence of immunogenicity, safety, and tolerability. Part B allows an evaluation of efficacy using the dose of POL-103A selected from Part A. The objective of the efficacy evaluation is to assess whether subjects randomized to the active arm have superior recurrence-free survival or overall survival (two primary endpoints) in the active arm compared to subjects randomized to the placebo arm. The safety of POL-103A will also be assessed.
For more information clinicaltrials.gov, NCT01546571.
- Histologically confirmed AJCC Stage IIB, IIC, or III melanoma
- Last definitive surgical resection of all clinically evident disease within 90 days of first POL-103A or placebo dosing. Subjects with positive margins of resection should have re-excision prior to randomization.
- Subjects with positive sentinel nodes must have a complete lymphadenectomy.
- Male or female subjects ≥ 18 and ≤ 80 years of age.
- Female subjects of childbearing potential must have a negative pregnancy test within 2 weeks of study randomization, must agree to use adequate contraception throughout the treatment duration and for 3 months after the last POL-103A or placebo dosing, and must not be breastfeeding.
- Any evidence of loco-regional or metastatic melanoma after definitive surgical resection, based on any of the following screening studies: a. Histological review of resected tumor , b. Physical examination findings, c. CT/PET scans of chest and abdomen, plus CT/PET scans of the pelvis for subjects with loco-regional disease below the waist, and CT/PET scans of the neck for subjects with disease in the head and neck region , d. Brain MRI or CT scan.
- ECOG Performance Status 0 or 1.
- White blood cell (WBC) count ≥ 4,000/mm3.
- Absolute neutrophil count ≥ 1,500/mm3.
- Hemoglobin ≥ 11 g/dL.
- Platelet count ≥ 100,000/mm3.
- Creatinine ≤ 2.0 mg/dL.
- Bilirubin ≤ 1.5 times the upper limit of normal (ULN).
- Albumin ≥ 3.5 mg/dL.
- Asparate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.0 times ULN.
- Subjects must have known BRAF mutation tumor status or have tumor tissue (fresh or archived sample) available for testing of BRAF mutation status (note: as long as it is confirmed that tumor tissue is available for testing, the subject may be considered eligible for the study; testing of BRAF mutation status on that tissue may be conducted at a later time during the study).
- Competent to comprehend, sign, and date an IEC/IRB-approved informed consent.
- Any prior melanoma treatment other than surgery or regional irradiation, including adjuvant or neoadjuvant treatment.
- Subjects who have a history of another malignancy within the past 5 years with the exception of adequately treated in situ squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the cervix. See treatment exclusions noted within the other exclusion criteria.
- Diagnosis of non-cutaneous melanoma or melanoma with unknown primary.
- Use of interferon or other biologic response modifiers (e.g., interleukin-2, colony-stimulating factors, other cytokines, BCG) within 60 days of first POL-103A or placebo dosing.
- Any evidence of loco-regional or metastatic melanoma after definitive surgical resection, based on any of the following screening studies: a. Histological review of resected tumor, b. Physical examination findings, c. CT/PET scans of chest and abdomen, plus CT/PET scans of the pelvis for subjects with loco-regional disease below the waist, and CT/PET scans of the neck for subjects with disease in the head and neck region, d. Brain MRI or CT scan.
- Chronic use of systemic corticosteroids or other immunosuppressants.
- Known allergy to alum.
- Prior use of any investigational agents within 30 days of first POL-103A or placebo dosing.
- History of any chronic medical or psychiatric condition or laboratory abnormality that, in the judgment of the principal investigator, may contraindicate study participation or study drug administration or may interfere with the interpretation of study results.
- Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures.
- Prior splenectomy.
- Known positivity for human immunodeficiency virus (HIV).
- Positive for antinuclear antibodies (ANA) at screening.
- Female subjects of childbearing potential not consenting to use adequate contraceptive precautions throughout the treatment duration and for 3 months after the last POL-103A or placebo dosing.
- Female subjects who are pregnant or lactating.
- Treatment Regimen
Subjects will be offered a Consent Form to allow screening and participation in the study. Subjects who meet all inclusion and exclusion criteria following screening will be randomized to receive either the vaccine or placebo on a 2:1 treatment allocation schedule. If the subject meets eligibility criteria s/he will be given treatment with the vaccine or placebo by intradermal injection. The study treatments will be administered 5 times at 2-week intervals, then 4 times at monthly intervals, then every 3 months until they have been treated for 2 years. Each subject will be treated with POL-103A or placebo unless one of the following occurs: development of recurrent disease that does not meet the criteria for continued dosing, death, subject withdrawal, or study termination, whichever comes first. Subjects will be monitored for disease progression and survival for up to 12 years after treatment is completed or discontinued.