Patient case: 74-year-old female with melanoma; genetic feature: no tumor infiltrating lymphocytes

Clinical trial: A Personalized Cancer Vaccine (NEO-PV-01) w/ Nivolumab for Patients With Melanoma, Lung Cancer or Bladder Cancer

Summary: The purpose of this study is to evaluate f the treatment with NEO-PV-01 + adjuvant in combination with nivolumab is safe and useful for patients with certain types of cancer. The study also will investigate if NEO-PV-01 + adjuvant with nivolumab may represent a substantial improvement over other available therapies such as nivolumab alone. All eligible patients will receive NEO-PV-01 + adjuvant and nivolumab while on this trial.

Detailed description: This clinical trial will enroll patients with metastatic or advanced melanoma, lung, or bladder cancer. The three agents being used in this study are:
  -  A new, investigational, personalized cancer vaccine called "NEO-PV-01"
  -  Poly-ICLC (Hiltonol), an investigational adjuvant that is used to help stimulate the immune system
  -  A cancer drug called nivolumab (OPDIVO®)
  These agents are considered immunotherapy and work by stimulating the immune system to fight cancer. NEO-PV-01 is a truly personalized vaccine therapy in that it is custom designed and manufactured to include targets for the immune system that are present uniquely on an individual's cancer. Poly-ICLC is an adjuvant that helps stimulate the immune system and make the vaccine, NEO-PV-01 more effective. Nivolumab helps T-cells, a certain type of immune cell, that recognize these targets to reach and attack the tumor. Nivolumab is in clinical development for treatment of bladder cancer and is approved by the FDA (the U.S. Food and Drug Administration) for the treatment of some lung, skin, kidney, and blood cancers.
  The purpose of this study is to find out if treatment with NEO-PV-01 + adjuvant in combination with nivolumab is safe and effective for patients with melanoma, lung, or bladder cancer. The study also will see if NEO-PV-01 vaccine + adjuvant with nivolumab can improve responses compared to available therapies such as nivolumab monotherapy The side effects of NEO-PV-01 + adjuvant and nivolumab will be monitored and additional research tests will be done to assess the immune response against each individual's cancer.

Eligibility: Inclusion Criteria:
  -  Willing and able to give written informed consent.
  -  Have histologically confirmed unresectable or metastatic Stage III or Stage IV melanoma having received no more than one prior systemic therapy; unresectable or metastatic Stage IIIB or Stage IV smoking-associated NSCLC having received no more than one prior systemic therapy; unresectable or metastatic transitional cell carcinoma of the bladder, urethra, ureter or renal pelvis having received no more than one prior systemic therapy.
  -  Have at least one site of disease measurable disease by RECIST v1.1 that has not been treated with local therapy within 6 months of study treatment.
  -  At least one site of disease must be accessible to provide repeat biopsies for tumor tissue for sequence and immunological analysis.
  -  Have ECOG PS of 0 or 1.
  -  Age ≥ 18 years.
  -  Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicity see below limits for inclusion) or 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 28 days prior to study treatment:
  -  White blood cell (WBC) count ≥ 3 × 10e3/mL
  -  Absolute neutrophil count (ANC) ≥ 1.5 × 10e3/mL
  -  Absolute lymphocyte count (ALC) ≥ 1 × 10e3/mL
  -  Platelet count ≥ 100 × 10e3/mL
  -  Hemoglobin > 9 g/dL
  -  Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min
  -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN
  -  Total bilirubin ≤ 1.5 × ULN (except in patients with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dL).
  -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 3 days prior to the start of nivolumab.
  -  Female participants, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, from screening through 5 months after the last dose of study treatment (including nivolumab single agent). Approved contraceptive methods include, for example: intrauterine device, diaphragm with spermicide, cervical cap with spermicide, male condom with spermicide, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.
  -  Men who are sexually active with women of child bearing potential must agree to use a condom from screening through 5 months after the last dose of study treatment (including nivolumab single agent). For NSCLC, patients must have a minimum of a 30 pack-year smoking history.
  Exclusion Criteria:
  -  Received therapy with any immunotherapeutic agents including, but not limited to, any anti-PD1 or anti-PDL1 antibody therapy, with this exception: Melanoma patients having received and progressed on anti-CTLA4 may participate in the trial.
  -  Received systemic anti-cancer therapy within 28 days of 1st dose of study therapy.
  -  Have known brain metastases or leptomeningeal metastases.
  -  Received non-oncology vaccine therapy for prevention of infectious diseases during the 4-week period prior to first dose of nivolumab therapy. Patients may not receive any non-oncology vaccine therapy during the period of NEO-PV-01 + adjuvant or nivolumab administration and until at least 8 weeks after the last dose of the booster vaccine.
  -  Have an active or history of autoimmune disease (known or suspected). Exceptions are permitted for vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring only hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  -  Have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the first dose of study drug (nivolumab). Inhaled or topical steroids and adrenal replacement doses (≤ 10 mg daily prednisone equivalents) are permitted in the absence of active autoimmune disease.
  -  Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illnesses unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with participation in this study.
  -  Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, or 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.
  -  Pregnant women are excluded from this study because nivolumab, personalized neoantigen peptides, and Poly-ICLC are agents with unknown risks to the developing fetus.
  -  Nursing women are excluded from this study because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with nivolumab, personalized neoantigen peptides, and Poly-ICLC.
  -  Have a history of an invasive malignancy, except for the following circumstance: individuals with a history of invasive malignancy 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 malignancy; individuals with the following cancers are eligible if diagnosed and treated carcinoma in situ of the breast, oral cavity or cervix, localized prostate cancer, basal cell or squamous cell carcinoma of the skin.
  -  Mucosal melanoma and uvueal melanoma.
  -  Patients with NSCLC and known anaplastic lymphoma kinase (ALK) translocations or epidermal growth factor receptor (EGFR) mutations who have not received prior treatment with ALK or EGFR inhibitor.

Relevance to patient case: not relevant