MelanomaPhase 1/2Mel64NCT02515227
Safety Study of a Helper Peptide Vaccine Plus Pembrolizumab
A Phase 1/2 study testing 6MHP and Pembrolizumab in people with Melanoma, run by Craig L Slingluff, Jr at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- 6MHP and Pembrolizumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 2016to 14 Mar 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with unresectable American Joint Committee on Cancer (AJCC) stage IIIB or stage 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
- Ability to provide written informed consent/assent for the trial.
- ≥18 years of age
- A subject may be naïve for immunotherapy agents or have received interferon-alpha, ipilimumab or other cytotoxic T lymphocyte antigen (CTLA)-4 antibody, Programmed death-1 (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:
- A patient who has experienced progression of melanoma during that therapy or after having completed that therapy,
- 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
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- 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 Positron emission tomography (PET)/CT fusion scan may replace scans of the chest, abdomen, and pelvis.
- 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.
- Subjects who have had brain metastases will be eligible if all of the following are true:
- Each brain metastasis must have been completely removed by surgery or each unresected brain metastasis must have been treated with stereotactic radiosurgery.
- There has been no evident growth of any brain metastasis since the most recent treatment
- 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.
- The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed ≥ 1 week prior to registration.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function.
- Two intact (undissected) axillary and/or inguinal lymph node basins.
Who cannot join
- 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 treatment.
- 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.
- Is currently receiving nitrosureas or has received this therapy within the preceding 6 weeks of first dose of treatment.
- 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
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- 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
- 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.
- 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 therapy.
- 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.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- 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 include:
- 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
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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.
- 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.
- Has received a live vaccine or allergy desensitization injections within 30 days prior to the first dose of trial treatment.
- Has known or suspected allergies to any component of the vaccine.
- Has been vaccinated previously with any of the synthetic peptides included in this protocol.
- Is classified according to the New York Heart Association classification as having Class III or IV heart disease (Appendix 12.5).
- Has uncontrolled diabetes, defined as having a HGBA1C > 7.5%.
- Has a body weight < 110 pounds (without clothes) at enrollment, due to the amount and frequency with which blood will be drawn.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
About this study
Official title: 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 samples.
- Conditions
- Melanoma
- Being tested
- 6MHP, Pembrolizumab
- Keywords
- peptide, vaccine, Montanide ISA-51, pembrolizumab, PD-1, KEYTRUDA
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6MHPBiological
Also called 6 melanoma helper peptide vaccine
6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides
PembrolizumabDrug
Also called KEYTRUDA, MK-3475
Humanized monoclonal antibody (mAb) specific for PD-1.
| Study group | Role | What they receive |
|---|---|---|
| 6MHP (6 Melanoma helper peptide) vaccine + Pembrolizumab | Experimental | 6MHP (200 mcg each peptide) will be administered intradermally and subcutaneously on days 1, 8, 15, 43, 64, and 85. Pembrolizumab (200 mg) will be administered intravenously every 3 weeks for up to 2 years, beginning on day 1. Receives: Biological: 6MHP; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities.
Number of participants with dose-limiting toxicities on treatment with combination of pembrolizumab and 6MHP.
Measured: 30 days after the last administration of study drug.
CD4+ T Cell Responses Detected in the Peripheral Blood or Vaccine-draining Lymph Node (Sentinel Immunized Node).
Circulating CD4+ T cell responses to 6MHP peptides were assessed using IFN-γ ELISpot assays directly ex vivo for peripheral blood mononuclear cells (PBMC) and sentinel immunized node (SIN) lymphocytes. For each sample, the following definitions applied: Nvax=number of T cells responding to vaccine peptide; Nneg=number of T cells responding to maximum negative control; Rvax=Nvax/Nneg. For PBMC, a participant was considered to have a T-cell response (Rsp) if all the following were true: (1) Nvax exceeded Nneg by ≥ 20/100,000 CD4+ cells (0.02%), (2) (Nvax-1 SD)≥(Nneg+1 SD), (3) Rvax ≥2×, and (4) Rvax postvaccine ≥2x Rvax prevaccine. Criteria for CD4+ Rsp in a SIN included criterion (1-3). A high durable T cell response (hdRsp) required a 5× increase above baseline in any two or more time points (through day 85), and a durable immune response (dRsp) required only a 2× increase over background. A response in either PBMC or in SIN is considered a response for this endpoint.
Measured: through week 104
Secondary outcomes (4)
Number of T Cells in the Tumor Microenvironment
Evaluation of tumor infiltration by T cells.Tumor biopsies were obtained pretreatment and day 22 for 12 participants and were evaluated with multiplex immunofluorescence histology (mIFH). CD8+ T cell data were evaluated. CD4+ T cells were not reported because of technical challenges with that antibody. These 12 participants with evaluable tumor samples included 3 on the PD-1 antibody-naive cohort, and 9 on the antibody-experienced cohort.
Measured: up to day 22
Level of Th1-dominant Immune Signatures in the Tumor Microenvironment
Evaluation of cytokine profile for CD4+ T cells in tumor microenvironment. Data for this outcome have not been collected due to completion of funding for this study.
Measured: up to day 22
Number of CD8+ T Cell Responses to Defined Melanoma Antigens
Evaluation of epitope-spreading through the measurement of the induction of CD8+ T cell responses to defined melanoma antigens.
Measured: up to week 104
Amount of IgG Antibody Specific for 6MHP as Measured in the Blood and the Sentinel Immunized Node
Evaluation of antibody responses to 6MHP
Measured: up to week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2015 (estimated)
- Study start6 Oct 2016
- Primary completion14 Mar 2020
- Study completion14 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Craig L Slingluff, Jr
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Craig L Slingluff, Jr, University of Virginia
- Investigators
- Craig L. Slingluff, Jr., MD, Study director, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02515227
- Sponsor's protocol ID
- 18174
- Other IDs
- R01CA178846
- Acronym
- Mel64
- Status last verified
- Aug 2023
- First submitted
- 30 Jul 2015
- Last updated
- 25 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial to Evaluate the Safety, Immunogenicity, and Clinical Activity of a Helper Peptide Vaccine Plus PD-1 Blockade
- ClinicalTrials.gov ID
- NCT02515227
- Acronym / sponsor ID
- Mel64 / 18174
- Conditions
- Melanoma
- Keywords
- peptide, vaccine, Montanide ISA-51, pembrolizumab, PD-1, KEYTRUDA
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Craig L Slingluff, JrUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 6 Oct 2016 (actual)
- Primary completion
- 14 Mar 2020 (actual)
- Study completion
- 14 Mar 2020 (actual)
- First posted
- 4 Aug 2015 (estimated)
- Results
- Posted 25 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 6MHP (6 Melanoma helper peptide) vaccine + Pembrolizumab | Experimental | Biological: 6MHP, Drug: Pembrolizumab6MHP (200 mcg each peptide) will be administered intradermally and subcutaneously on days 1, 8, 15, 43, 64, and 85. Pembrolizumab (200 mg) will be administered intravenously every 3 weeks for up to 2 years, beginning on day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Subjects with unresectable American Joint Committee on Cancer (AJCC) stage IIIB or stage 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
- Ability to provide written informed consent/assent for the trial.
- ≥18 years of age
- A subject may be naïve for immunotherapy agents or have received interferon-alpha, ipilimumab or other cytotoxic T lymphocyte antigen (CTLA)-4 antibody, Programmed death-1 (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:
- Measurable disease based on RECIST 1.1.
Key exclusion criteria (34 listed)
- 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 treatment.
- 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.
- Is currently receiving nitrosureas or has received this therapy within the preceding 6 weeks of first dose of treatment.
- 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):
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 6MHPAlso: 6 melanoma helper peptide vaccine6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides | Biological | 6MHP (6 Melanoma helper peptide) vaccine + Pembrolizumab |
| PembrolizumabAlso: KEYTRUDA, MK-3475Humanized monoclonal antibody (mAb) specific for PD-1. | Drug | 6MHP (6 Melanoma helper peptide) vaccine + Pembrolizumab |
Primary outcome
Number of Participants With Dose-limiting Toxicities.
Time frame: 30 days after the last administration of study drug.
Number of participants with dose-limiting toxicities on treatment with combination of pembrolizumab and 6MHP.
CD4+ T Cell Responses Detected in the Peripheral Blood or Vaccine-draining Lymph Node (Sentinel Immunized Node).
Time frame: through week 104
Circulating CD4+ T cell responses to 6MHP peptides were assessed using IFN-γ ELISpot assays directly ex vivo for peripheral blood mononuclear cells (PBMC) and sentinel immunized node (SIN) lymphocytes. For each sample, the following definitions applied: Nvax=number of T cells responding to vaccine peptide; Nneg=number of T cells responding to maximum negative control; Rvax=Nvax/Nneg. For PBMC, a participant was considered to have a T-cell response (Rsp) if all the following were true: (1) Nvax exceeded Nneg by ≥ 20/100,000 CD4+ cells (0.02%), (2) (Nvax-1 SD)≥(Nneg+1 SD), (3) Rvax ≥2×, and (4) Rvax postvaccine ≥2x Rvax prevaccine. Criteria for CD4+ Rsp in a SIN included criterion (1-3). A high durable T cell response (hdRsp) required a 5× increase above baseline in any two or more time points (through day 85), and a durable immune response (dRsp) required only a 2× increase over background. A response in either PBMC or in SIN is considered a response for this endpoint.
4 secondary outcomes
Number of T Cells in the Tumor Microenvironment
Time frame: up to day 22
Level of Th1-dominant Immune Signatures in the Tumor Microenvironment
Time frame: up to day 22
Number of CD8+ T Cell Responses to Defined Melanoma Antigens
Time frame: up to week 104
Amount of IgG Antibody Specific for 6MHP as Measured in the Blood and the Sentinel Immunized Node
Time frame: up to week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig L. Slingluff, Jr., MD study director
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 6MHP and Pembrolizumab in people with Melanoma, run by Craig L Slingluff, Jr at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities. (time frame: 30 days after the last administration of study drug.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2023.