Delving into the Latest Updates on Melanoma helper peptide vaccine(National Cancer Institute) with Synapse

Overview

Basic Info

Drug Type

Therapeutic vaccine

Synonyms-

Target-

Mechanism

Immunostimulants

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Melanoma

Originator Organization

National Cancer Institute

Active Organization-

Inactive Organization

Eastern Cooperative Oncology Group

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells.
PURPOSE: This randomized phase II trial is studying four different vaccines using melanoma peptides from cytotoxic T cells and helper T cells to see how well they work in treating patients with metastatic melanoma.

Start Date09 May 2005

Sponsor / Collaborator

Eastern Cooperative Oncology Group

[+1]

NCT00118274 / CompletedPhase 1/2IIT

A Multicenter Trial to Evaluate the Effects of Administration of Cyclophosphamide and Melanoma-Derived Helper Peptides on the Immunogenicity of a Class I MHC-Restricted Peptide-Based Vaccine in Participants With Resected Melanoma

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclophosphamide may also stimulate the immune system in different ways and stop tumor cells from growing. Giving vaccine therapy together with cyclophosphamide after surgery may cause a stronger immune response to kill any remaining tumor cells. It may also prevent or delay the recurrence of melanoma.
PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy when given with or without cyclophosphamide and to see how well they work in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.

Start Date01 Mar 2005

Sponsor / Collaborator

University of Virginia

[+1]

100 Clinical Results associated with Melanoma helper peptide vaccine(National Cancer Institute)

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100 Translational Medicine associated with Melanoma helper peptide vaccine(National Cancer Institute)

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100 Patents (Medical) associated with Melanoma helper peptide vaccine(National Cancer Institute)

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18

Literatures (Medical) associated with Melanoma helper peptide vaccine(National Cancer Institute)

01 Nov 2022·Journal for ImmunoTherapy of Cancer

Correction: Phase I/II clinical trial of a helper peptide vaccine plus PD-1 blockade in PD-1 antibody-naïve and PD-1 antibody-experienced patients with melanoma (MEL64)

Article

01 Sep 2022·Journal for ImmunoTherapy of Cancer

Phase I/II clinical trial of a helper peptide vaccine plus PD-1 blockade in PD-1 antibody-naïve and PD-1 antibody-experienced patients with melanoma (MEL64)

Article

Author: Slingluff, Craig L ; Haden, Kathleen ; Dengel, Lynn T ; Petroni, Gina R ; Olson, Walter C ; Chianese-Bullock, Kimberly A ; Grosh, William W ; Vavolizza, Rick Daniel ; Gaughan, Elizabeth M ; Mauldin, Ileana S ; Varhegyi, Nikole ; Kaur, Varinder ; Smith, Kelly T

BackgroundA vaccine containing 6 melanoma-associated peptides to stimulate helper T cells (6MHP) is safe, immunogenic, and clinically active. A phase I/II trial was designed to evaluate safety and immunogenicity of 6MHP vaccines plus programmed death 1 (PD-1) blockade.Participants and methodsParticipants with advanced melanoma received 6MHP vaccines in an incomplete Freund’s adjuvant (6 vaccines over 12 weeks). Pembrolizumab was administered intravenously every 3 weeks. Tumor biopsies at baseline and day 22 were analyzed by multiplex immunohistochemistry. Primary end points were safety (Common Terminology Criteria for Adverse Events V.4.03) and immunogenicity (ex vivo interferon-γ ELISpot assay). Additional end points included changes in the tumor microenvironment (TME) and clinical outcomes.ResultsTwenty-two eligible participants were treated: 6 naïve to PD-1 antibody (Ab) and 16 PD-1 Ab-experienced. Median follow-up was 24.4 months. Most common treatment-related adverse events (any grade) included injection site reactions, fatigue, anemia, lymphopenia, fever, elevated aspartate aminotransferase, pruritus, and rash. Treatment-related dose-limiting toxicities were observed in 3 (14%) participants, which did not cross the study safety bound. A high durable T cell response (Rsp) to 6MHP was detected in only one participant, but twofold T cell Rsps to 6MHP were detected in 7/22 (32%; 90% CI (16% to 52%)) by week 13. Objective clinical responses were observed in 23% (1 complete response, 4 partial responses), including 4/6 PD-1 Ab-naïve (67%) and 1/16 PD-1 Ab-experienced (6%). Overall survival (OS) was longer for PD-1 Ab-naïve than Ab-experienced participants (HR 6.3 (90% CI (2.1 to 28.7)). In landmark analyses at 13 weeks, OS was also longer for those with T cell Rsps (HR 6.5 (90% CI (2.1 to 29.2)) and for those with objective clinical responses. TME evaluation revealed increased densities of CD8+T cells, CD20+B cells, and Tbet+cells by day 22.ConclusionsTreatment with the 6MHP vaccine plus pembrolizumab was safe, increased intratumoral lymphocytes, and induced T cell Rsps associated with prolonged OS. The low T cell Rsp rate in PD-1 Ab-experienced participants corroborates prior murine studies that caution against delaying cancer vaccines until after PD-1 blockade. The promising objective response rate and OS in PD-1 Ab-naïve participants support consideration of a larger study in that setting.

01 Jan 2021·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Trial to evaluate the immunogenicity and safety of a melanoma helper peptide vaccine plus incomplete Freund’s adjuvant, cyclophosphamide, and polyICLC (Mel63)

Q2 · MEDICINE

ArticleOA

Author: Dickinson, Anna ; Gaughan, Elizabeth M ; Chianese-Bullock, Kimberly A ; Varhegyi, Nikole ; Wages, Nolan A ; Smolkin, Mark ; Dengel, Lynn T ; Olson, Walter C ; Kaur, Varinder ; Slingluff, Craig L ; Petroni, Gina R ; Grosh, William W ; Haden, Kathleen ; Reed, Caroline ; Galeassi, Nadejda V ; Hall, Emily H ; Deacon, Donna ; Smith, Kelly T

BackgroundPeptide vaccines designed to stimulate melanoma-reactive CD4+ T cells can induce T cell and antibody (Ab) responses, associated with enhanced overall survival. We hypothesized that adding toll-like receptor 3 agonist polyICLC to an incomplete Freund’s adjuvant (IFA) would be safe and would support strong, durable CD4+ T cell and Ab responses. We also hypothesized that oral low-dose metronomic cyclophosphamide (mCy) would be safe, would reduce circulating regulatory T cells (T-regs) and would further enhance immunogenicity.Participants and methodsAn adaptive design based on toxicity and durable CD4+ T cell immune response (dRsp) was used to assign participants with resected stage IIA-IV melanoma to one of four study regimens. The regimens included a vaccine comprising six melanoma peptides restricted by Class II MHC (6MHP) in an emulsion with IFA alone (Arm A), with IFA plus systemic mCy (Arm B), with IFA+ local polyICLC (Arm C), or with IFA+ polyICLC+ mCy (Arm D). Toxicities were recorded (CTCAE V.4.03). T cell responses were measured by interferon γ ELIspot assay ex vivo. Serum Ab responses to 6MHP were measured by ELISA. Circulating T-regs were assessed by flow cytometry.ResultsForty-eight eligible participants were enrolled and treated. Early data on safety and dRsp favored enrollment on arm D. Total enrollment on Arms A-D were 3, 7, 6, and 32, respectively. Treatment-related dose-limiting toxicities (DLTs) were observed in 1/7 (14%) participants on arm B and 2/32 (6%) on arm D. None exceeded the 25% DLT threshold for early closure to enrollment for any arm. Strong durable T cell responses to 6MHP were detected ex vivo in 0%, 29%, 67%, and 47% of participants on arms A-D, respectively. IgG Ab responses were greatest for arms C and D. Circulating T-regs frequencies were not altered by mCy.Conclusions6MHP vaccines administered with IFA, polyICLC, and mCy were well tolerated. The dRsp rate for arm D of 47% (90% CI 32 to 63) exceeded the 18% (90% CI 11 to 26) rate previously observed with 6MHP in IFA alone. Vaccination with IFA+ polyICLC (arm C) also showed promise for enhancing T cell and Ab responses.

100 Deals associated with Melanoma helper peptide vaccine(National Cancer Institute)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	Phase 2	US	Eastern Cooperative Oncology Group	06 Nov 2003

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Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00118274 (CTgov)	Phase 1/2	Melanoma, Cutaneous Malignant	170	multi-epitope melanoma peptide vaccine+tetanus toxoid helper peptide (Arm I)	mbwradoxgl(supluabpww) = dbhrgtxkfc wmyazaccbs (qceqqmyvnq, phyywpusch - iivcpcxxyj) View more	-	20 Apr 2021
				multi-epitope melanoma peptide vaccine+cyclophosphamide+tetanus toxoid helper peptide (Arm II)	mbwradoxgl(supluabpww) = yjpzcpmxsw wmyazaccbs (qceqqmyvnq, zlwribopuu - xfbgykwmuo) View more
NCT00071981 (CTgov)	Phase 2	Melanoma, Cutaneous Malignant \| Metastatic melanoma	175	multi-epitope melanoma peptide vaccine+sargramostim (Arm I (12MP))	azhlqozrko(etjurdwhfh) = qhochjqjfe msnuxfugip (kbsabzkqii, mqvcjumvgi - fnvbacmege) View more	-	03 Jan 2013
				multi-epitope melanoma peptide vaccine+sargramostim (Arm II (12MP/Tet))	azhlqozrko(etjurdwhfh) = gcsnnzdgxn msnuxfugip (kbsabzkqii, nhcwbbjamd - ntleocnimn) View more