Safety Study of a Helper Peptide Vaccine Plus Pembrolizumab

Conditions:Skin Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:November 2015
End Date:August 2021
Contact:Jessica Zareno, MS

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A Trial to Evaluate the Safety, Immunogenicity, and Clinical Activity of a Helper Peptide Vaccine Plus PD-1 Blockade

This study evaluates whether it is safe to administer a peptide vaccine in combination with
pembrolizumab. This study will also evaluate the effects of the combination of the peptide
vaccine and pembrolizumab on the immune system. The investigators will monitor these effects
by performing tests in the laboratory on participants' blood, a lymph node, and tumor

Inclusion Criteria:

1. Subjects with unresectable stage IIIB or IIIC melanoma, or stage IV metastatic
melanoma that have clinical or radiological evidence of disease. Subjects may have had
cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Staging
must be confirmed by cytological or histological examination. Staging of cutaneous
melanoma will be based on the revised AJCC staging system

2. Ability to provide written informed consent/assent for the trial.

3. ≥18 years of age

4. A subject may be naïve for immunotherapy agents or have received interferon-alpha,
ipilimumab or other CTLA-4 antibody, PD-1 antibody (or anti-PD-L1 antibody),
interleukin-2, or prior cancer vaccines other than the 6MHP vaccine. Patients who have
received a PD-1/PD-L1 antibody may be enrolled in either of the following settings:

1. A patient who has experienced progression of melanoma during that therapy or
after having completed that therapy,

2. A patient who fails to experience an objective clinical response (partial
response or complete response by RECIST 1.1 criteria) after either 12 weeks of
continuous anti-PD1 antibody or anti-CTLA4/anti-PD1 combination therapy, and is a
candidate to receive pembrolizumab therapy

5. Measurable disease based on RECIST 1.1.

Subjects will be required to have radiological studies to define radiologically
evident disease. Required studies include:

- Chest CT scan,

- Abdominal and pelvic CT scan, and

- Head CT scan or MRI PET/CT fusion scan may replace scans of the chest, abdomen,
and pelvis.

6. Subjects who have metastatic melanoma available for biopsy pretreatment and on day 22
must consent to having those biopsies. These metastases may be in nodes, skin, soft
tissue, liver, or other sites that can be accessed safely by needle biopsy, incisional
or excisional biopsy, with or without image guidance. The lesions to be biopsied must
be specified at study enrollment and not included as target lesions for RECIST
calculations. In instances where disease that is accessible to biopsy is limited,
archival tissue specimens collected after a subject's last systemic therapy may be
used for baseline measures.

Subjects must have measurable disease in addition to the lesion(s) to be biopsied.

7. Subjects who have had brain metastases will be eligible if all of the following are

- Each brain metastasis must have been completely removed by surgery or each
unresected brain metastasis must have been treated with stereotactic

- There has been no evident growth of any brain metastasis since the most recent

- No brain metastasis is > 2 cm in diameter at the time of registration.

- Neurologic symptoms have returned to baseline,

- There is no evidence of new or enlarging brain metastases,

- Subjects are not using steroids for at least 7 days prior to registration.

8. The most recent surgical resections or gamma-knife therapy for malignant melanoma must
have been completed ≥ 1 week prior to registration.

9. ECOG performance status of 0 or 1

10. Adequate organ function.

11. Two intact (undissected) axillary and/or inguinal lymph node basins.

Exclusion Criteria

1. Is currently participating in or has participated in a study of an investigational
agent or using an investigational device within 4 weeks of the first dose of

2. Is currently receiving Interferon (e.g. Intron-A®), growth factors (e.g. Procrit®,
Aranesp®, Neulasta®), or interleukins (e.g. Proleukin®), or has received these agents
within 4 weeks of the first dose of treatment.

3. Is currently receiving nitrosureas or has received this therapy within the preceding 6
weeks of first dose of treatment.

4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment with the following exceptions (which are permitted):

- replacement steroid doses in patients with adrenal or pituitary insufficiency

- Intra-articular steroid injections

- Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) at low doses (less than 500
mcg fluticasone per day, or equivalent)

- Topical and nasal corticosteroids

- Non-steroidal anti-inflammatory drugs

5. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents
administered more than 4 weeks earlier.

6. Has had prior chemotherapy, targeted small molecule therapy, or external beam
radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e.,
≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and
may qualify for the study.

- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting

7. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include carcinoma in situ of the breast (DCIS or LCIS), basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer
that has undergone potentially curative therapy.

8. Has known active central nervous system (CNS) metastases and/or carcinomatous

9. Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids or immunosuppressive agents. Exceptions to this criterion

- Subjects with vitiligo or other depigmenting illness.

- Resolved childhood asthma/atopy

- Intermittent use of bronchodilators or local steroid injections

- Hypothyroidism stable on hormone replacement or Sjogren's syndrome

- The presence of laboratory evidence of autoimmune disease (e.g. positive ANA
titer) without symptoms

- Mild arthritis requiring NSAID medications

10. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

11. Has an active infection requiring systemic therapy.

12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.

13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

14. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.

15. Is HIV positive or has evidence of active Hepatitis C virus (testing to be done within
6 months of study entry) or active Hepatitis B virus.

16. Has received a live vaccine or allergy desensitization injections within 30 days prior
to the first dose of trial treatment.

17. Has known or suspected allergies to any component of the vaccine.

18. Has been vaccinated previously with any of the synthetic peptides included in this

19. Is classified according to the New York Heart Association classification as having
Class III or IV heart disease (Appendix 12.5).

20. Has uncontrolled diabetes, defined as having a HGBA1C > 7.5%.

21. Has a body weight < 110 pounds (without clothes) at enrollment, due to the amount and
frequency with which blood will be drawn.
We found this trial at
1300 Jefferson Park Avenue
Charlottesville, Virginia 22908
Principal Investigator: Craig L. Slingluff, MD
Phone: 434-924-1730
University of Virginia Cancer Center We are fortunate in having state of the art clinical...
Charlottesville, VA
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