The primary purpose of this study is to demonstrate that the NEO-PV-01 vaccine, either with
APX005M or ipilimumab, and nivolumab is safe for the treatment of patients with advanced or
metastatic melanoma. The study will also investigate an alternative schedule for the
administration of the NEO-PV-01 vaccine. Study interventions will be assessed by both
clinical and immune responses to treatment.
This clinical trial will enroll patients with advanced or metastatic melanoma not having
received treatment for metastatic disease. The 5 agents being used in this study are:
- A new, investigational, personal cancer vaccine called "NEO-PV-01".
- Poly-ICLC (Hiltonol), an investigational adjuvant that is used to help stimulate the
- A cancer drug called APX005M, a drug that stimulates specific types of immune cells that
help the immune system to recognize specific targets.
- A cancer drug called ipilimumab
- A cancer drug called nivolumab
NEO-PV-01, APX005M, ipilimumab, and nivolumab are considered immunotherapies and work using
the immune system to fight cancer. NEO-PV-01 is a personal vaccine therapy in that it is
manufactured specifically to include targets for the immune system that are present uniquely
on your cancer. Poly-ICLC is an adjuvant that helps stimulate the immune system and make the
vaccine, NEO-PV-01, more effective.
The purpose of this study is to find out if treatment with NEO-PV-01 + Poly-ICLC (the
NEO-PV-01 vaccine) in combination with either APX005M or ipilimumab, and nivolumab is safe
and useful for patients with melanoma. The study also will assess if the NEO-PV-01 vaccine,
when given at different intervals, can improve your response compared with the standard
schedule. This study will also assess the effects of poly-ICLC in combination with nivolumab.
The side effects of all study drugs will be monitored and additional research tests will be
done to assess your immune response to your cancer. There is no guarantee that you will
benefit from therapy with the study drugs.
The FDA has not yet approved the NEO-PV-01 vaccine for use alone or in combination with other
cancer drugs such as APX005M, ipilimumab, and nivolumab. Neither APX005M nor Poly-ICLC are
approved for use in your type of cancer. Ipilimumab and nivolumab are both approved for use
in your type of cancer.
- Willing and able to give written informed consent.
- Age ≥ 18 years.
- Have cytologically or histologically confirmed advanced or metastatic melanoma and
having received no prior systemic therapy for metastatic disease.
- Have at least 1 site of disease measurable by RECIST 1.1 that has not been treated
with local therapy within 6 months of study treatment. Tumor lesions situated in a
previously irradiated area are considered measurable if progression has been
demonstrated in such lesions.
- Have at least 1 site of disease accessible to repeat biopsies for tumor sequencing and
immunological analysis. This site may be a target lesion as long as it will not become
unmeasurable by the biopsy procedure.
- Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 with an
anticipated life expectancy of > 6 months.
- Recovered from all toxicities associated with prior treatment to acceptable baseline
status (for laboratory toxicities, see below limits for inclusion) or a National
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version
4.03, Grade of 0 or 1, except for toxicities not considered a safety risk (e.g.,
alopecia or vitiligo).
- Screening laboratory values must meet the following criteria and should be obtained
within 30 days (or 45 days if a biopsy is repeated) prior to study treatment:
1. White blood cell (WBC) count ≥ 3 × 103/µL
2. Platelet count ≥ 100 × 103/µL
3. Hemoglobin > 9 g/dL
4. Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
or ≤ 5 × ULN for patients with liver metastases
6. Total bilirubin ≤ 1.5 × ULN (except in patients with Gilbert Syndrome who can
have total bilirubin < 3.0 mg/dL).
- Female patients of childbearing potential must have a negative serum or urine
pregnancy test within 7 days prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
- Female patients of childbearing potential must be willing to use an adequate method of
contraception, as outlined in the protocol, for the course of the study through 120
days after last dose of study medication.
- Male patients of childbearing potential must agree to use an adequate method of
contraception, as outlined in the protocol, starting with the first dose of study
therapy through 120 days after the last dose of study therapy. Abstinence is
acceptable if this is the usual lifestyle and preferred contraception for the patient.
- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of first dose of treatment.
- Received any systemic therapy for advanced or metastatic cancer treatment including
immunotherapeutic agents such as anti-programmed cell death protein 1 (anti-PD-1),
anti-PD-L1, anti-CD40, or anti-cytotoxic T-lymphocyte-associated antigen 4
(anti-CTLA-4) antibody therapy.
- Have had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AE due to agents
administered more than 4 weeks earlier.
- Have had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 30 days prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
baseline) from AEs due to a previously administered agent.
1. Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception
to this criterion and may qualify for the study.
2. Note: If patients received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
- Received radiation therapy at the biopsy sites.
- Received prior tyrosine kinase inhibitor therapy or palliative radiation within 7 days
of Cycle 1/Day 1.
- Have known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging [using the identical
imaging modality for each assessment, either magnetic resonance imaging (MRI) or
computed tomography (CT) scan] for at least 4 weeks prior to the first dose of trial
treatment and any neurologic symptoms have returned to baseline), have no evidence of
new or enlarging brain metastases, and are not using steroids for at least 7 days
prior to trial treatment. This exception does not include carcinomatous meningitis,
which is excluded regardless of clinical stability.
- Have active autoimmune disease that has required systemic treatment in the past 2
years (i.e., with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)
is not considered a form of systemic treatment.
- Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
The use of physiologic doses of corticosteroids may be approved after consultation
with the Sponsor.
- Received a live vaccination within 30 days of planned treatment start date.
- Have an active infection requiring systemic therapy.
- Have a history of sensitivity or allergy to mAbs or immunoglobulin G (IgG).
- Have a history of allogeneic bone marrow transplantation.
- Have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Have known active Hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
Hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is detected).
- Have an uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection requiring treatment, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia.
- Have any underlying medical condition, psychiatric condition, or social situation
that, in the opinion of the Investigator, would compromise study administration as per
protocol or compromise the assessment of AEs.
- Have a planned major surgery.
- Are pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.
- Nursing women are excluded from this study because there is an unknown but potential
risk of AEs in nursing infants secondary to treatment of the mother with nivolumab,
personalized neoantigen peptides, adjuvant, ipilimumab, and APX005M.
- Have a history of additional invasive metastatic disease (other than melanoma), except
for the following:
1. Individuals with a history of invasive metastatic disease are eligible if they
have been disease free for at least 2 years and are deemed by the Investigator to
be at low risk for recurrence of that metastatic disease;
2. Individuals with basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, in situ cervical cancer, or local papillary thyroid cancer, who have
undergone therapy with curative intent.
- Have severe hypersensitivity (≥ Grade 3) to nivolumab and/or any of its excipients.
- Have mucosal melanoma, uveal melanoma, or acral lentiginous melanoma.