Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Vaccines

Immunoglobulins

Monatide (IMS 3015)

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

6MHP

Humanized monoclonal antibody (mAb) specific for PD-1.

Craig L. Slingluff, Jr., MD

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.

Safety Study of a Helper Peptide Vaccine Plus Pembrolizumab

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

Number of participants with dose-limiting toxicities on treatment with combination of pembrolizumab and 6MHP.

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.

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.

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.

Evaluation of epitope-spreading through the measurement of the induction of CD8+ T cell responses to defined melanoma antigens.

National Cancer Institute (NCI)

Craig L Slingluff, Jr

Director, Human Immune Therapy Center

Participants who had not previously received a PD-1 or PD-L1 antibody were eligible for this cohort.

They received 6MHP vaccine (200 mcg each peptide) emulsified in Montanide ISA-51 adjuvant and administered intradermally and subcutaneously on days 1, 8, 15, 43, 64, and 85. Pembrolizumab (200 mg) was administered intravenously every 3 weeks for up to 2 years, beginning on day 1.

6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

Pembrolizumab: Humanized monoclonal antibody (mAb) specific for PD-1.

6MHP + Pembrolizumab (PD-1 Antibody-naive Cohort)

Participants who had previously received a PD-1 or PD-L1 antibody were eligible for this cohort.

They received 6MHP vaccine (200 mcg each peptide) emulsified in Montanide ISA-51 adjuvant and administered intradermally and subcutaneously on days 1, 8, 15, 43, 64, and 85. Pembrolizumab (200 mg) was administered intravenously every 3 weeks for up to 2 years, beginning on day 1.

6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

Pembrolizumab: Humanized monoclonal antibody (mAb) specific for PD-1.

6MHP + Pembrolizumab (PD-1 Antibody-experienced Cohort)

Total

Age at enrollment

Age, Customized

Sex: Female, Male

Race at Enrollment

Race/Ethnicity, Customized

United States

Region of Enrollment

This measure of performance status refers to a scale from 0 to 5. Grade 0 refers to normal health with full activity and normal activity performance. Grade 1 refers to the status where individuals are restricted in strenuous activity but they are ambulatory and able to perform light or sedentary work. Eligibility for this trial required ECOG performance status of 0 to 1.

ECOG Performance Status

Craig Slingluff, MD

DLT was defined as unexpected adverse event (AE) at least possibly related to treatment, and, for 6MHP, grade ≥3 hematological or non-hematological toxicity, except that vaccine site ulcers were considered DLTs if ulcer \>2cm, required antibiotics or debridement; and for pembrolizumab, required permanent discontinuation per specified guidelines. Also considered DLTs were selected grade ≥2 ocular AEs, and AEs that led to stopping treatment even if they did not meet prespecified DLT criteria.

Number of Participants With Dose-limiting Toxicities.

CD4 T cell response (Rsp)

CD4 high durable T cell response (hdRsp)

CD4 durable T cell response (dRsp)

CD4+ T Cell Responses Detected in the Peripheral Blood or Vaccine-draining Lymph Node (Sentinel Immunized Node).

CD8 T cells per mm^2 in day 0 tumor

CD8+ T cells per mm^2 in day 22 tumor

Participants received 6MHP vaccine (200 mcg each peptide) emulsified in Montanide ISA-51 adjuvant and administered intradermally and subcutaneously on days 1, 8, 15, 43, 64, and 85. Pembrolizumab (200 mg) was administered intravenously every 3 weeks for up to 2 years, beginning on day 1.

6MHP: 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

Pembrolizumab: Humanized monoclonal antibody (mAb) specific for PD-1.

6MHP + Pembrolizumab (PD-1-experienced Cohort)

Number of T Cells in the Tumor Microenvironment

Immune signature data have not been collected from the tumor microenvironment.

Level of Th1-dominant Immune Signatures in the Tumor Microenvironment

Due to completion of funding for this study, data have not been collected to assess epitope-spreading through the measurement of the induction of CD8+ T cell responses to defined melanoma antigens.

Number of CD8+ T Cell Responses to Defined Melanoma Antigens

Antibody responses to 6MHP have not been measured, due to completion of funding for this trial.

Spots Global Cancer Trial Database for Safety Study of a Helper Peptide Vaccine Plus Pembrolizumab

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial