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

Vaccines

No clinical response (PD de novo) after a minimum of 3 months on CPI monotherapy

Develop PD after initial clinical response to CPI monotherapy

Stable disease for at least 6 months on CPI monotherapy

Tumor Lysate, Particle Loaded, Dendritic Cell Vaccine

TLPLDC Vaccine

George Peoples, MD

Assess the safety and tumor response of utilizing an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine given in combination with standard of care (SoC) checkpoint inhibitors (CPI) in patients with stage IV melanoma with measurable disease.

Metastatic melanoma patients eligible for (or currently on) CPI therapy per SoC will be identified and screened for inclusion/exclusion criteria. Eligible patients will be counseled and consented for tissue procurement. They will undergo excisional or core needle biopsy as clinically indicated and this tissue will be shipped in liquid nitrogen shippers through FedEx to our central facility in Greenville, SC.The tumor will be stored frozen until vaccine preparation. Vaccine development requires 48 hours for preparation. Upon verification that adequate tissue was obtained, these patients will then be counseled and consented for participation in the trial.

The patients who qualify for participation in this trial will continue their treatment of CPI. Once consented, patients will receive a single injection of Neupogen (G-CSF) 300 μg SQ 24-48 hrs prior to having 70 mL of blood collected and sent to our central facility for DC isolation and preparation. Those who cannot tolerate Neupogen or refuse it will have 120 mL of blood drawn and sent. Additional blood may be drawn if additional vaccine doses need to be made or re-made for any reason. Vaccines will be prepared by producing TL through freeze/thaw cycling and then loaded into pre-prepared YCWP. The TL-loaded YCWP will be introduced to the DC for phagocytosis thus creating the TLPLDC vaccine, which will be frozen in single dose vials. Each vial will contain 1 x 106 TLPLDC and will be labeled with the patient's unique study number.

The frozen autologous TLPLDC will be sent back to the site with a total of 6 single dose vials after the vaccine has completed QA/QC testing and lot-release (usually 3 weeks). The primary vaccination series will include monthly inoculations at 0, 1, 2, 3 months followed by boosters at 6 and 9 months in the same lymph node draining area (preferably the anterior thigh). Once received, the first inoculation should occur within 4 weeks.

Safety data will be collected on local and systemic toxicities and graded and reported per the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

Patients will follow-up at their respective sites for evaluation of metastatic disease per SoC. They will under imaging, CT/PET-CT, to meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 and iRECIST to monitor disease.

Blood (50 mL) will be collected from all patients prior to each inoculation and at 12 months from enrollment for a total of 7 time points or a total of 350 mL of blood over 1 year. The collected blood will be sent to our central facility for immunologic testing of T-cell responses.

Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease.

Safety of adding the TLPLDC vaccine to SoC CPI monotherapy

RECIST criteria is used for assessing tumor response in the addition of TLPLDC vaccine. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

LumaBridge

Elios Therapeutics, LLC

Imaging was done with the same modality that was used for baseline measurements, to meet RECIST criteria (5) Time to the best overall response was determined from the date of first inoculation until the first day that the tumor meets RECIST criteria for a particular tumor response

TLPLDC Vaccine: Tumor Lysate, Particle Loaded, Dendritic Cell Vaccine

Treatment Group

Treatment

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Timothy Vreeland, MD

The safety evaluation of TLPLDC was the primary endpoint of this phase 1 trial. There were 26 patients enrolled, and 16 received at least one dose of vaccine. The population used for the safety analysis included these 16 patients. Toxicity was graded per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

A total of 60 inoculations of TLPLDC were given to 16 patients, with the median of 3.5 inoculations.

Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Patient

AEs related to TLPLDC

Total AEs

Serious AEs or Deaths

Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Number of AEs

No Clinical Response

Progressive Disease

Stable Disease

Not RECIST evaluable

Of 26 patients enrolled, 16 received at least one inoculation with the TLPLDC vaccine; The 16 patients who received at least one inoculation were included in the efficacy analysis

Spots Global Cancer Trial Database for tlpldc vaccine