Metastatic Melanoma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGTLPLDC Vaccine
Tumor Lysate, Particle Loaded, Dendritic Cell Vaccine
Sponsors
LumaBridge
Elios Therapeutics, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix A) * Metastatic melanoma eligible for {or currently on} standard of care CPI therapy (treating physician's choice) with measurable disease. * Approximately 1 cm3 preferred but 1 mg minimum of accessible and dispensable tumor (minimum of 3 passes with a core needle) * Able to tolerate CPI treatment regimen {if already started} * Adequate organ function as determined by the following laboratory values: * ANC ≥ 1,000/μL * Platelets ≥ 75,000/μL * Hgb ≥ 9 g/dL * Creatinine ≤ 1.5 x upper limit of normal (ULN) or Creatinine clearance ≥ 50% of lower limit of normal (LLN) * Total bilirubin ≤ 1.5 ULN * ALT and AST ≤ 1.5 ULN * For women of child-bearing potential, agreement to use adequate birth control (abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral contraception, IUD, or use of condoms or diaphragms)
Exclusion criteria
* Inability to tolerate CPI therapy {if already started} * Rapidly progressing multi-focal metastatic melanoma * Insufficient tumor available to produce vaccine * ECOG \>2 performance status (Appendix A) * Immune deficiency disease or known history of HIV, HBV, HCV * Receiving immunosuppressive therapy including chronic steroids (except physiologic maintenance doses), methotrexate, or other known immunosuppressive agents * Pregnancy (assessed by urine HCG) * Breast feeding * Active pulmonary disease requiring medication to include multiple inhalers (\>2 inhalers and one containing steroids) * Involved in other experimental protocols (except with permission of the other study PI)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Patient | 12 months (1 year) | Safety of adding the TLPLDC vaccine to SoC CPI monotherapy |
| Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Number of AEs | 12 months (1 year) | Safety of adding the TLPLDC vaccine to SoC CPI monotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response to Treatment Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | 12 months (1 year) | 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. |
Countries
United States
Participant flow
Pre-assignment details
All enrollees evaluated across all arms.
Participants by arm
| Arm | Count |
|---|---|
| Treatment TLPLDC Vaccine: Tumor Lysate, Particle Loaded, Dendritic Cell Vaccine | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
| Overall Study | ineligible | 3 |
| Overall Study | Lack of Efficacy | 10 |
| Overall Study | Not RECIST Measurable | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 16 |
| other Total, other adverse events | 12 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Number of AEs
Safety of adding the TLPLDC vaccine to SoC CPI monotherapy
Time frame: 12 months (1 year)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group | Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Number of AEs | AEs related to TLPLDC | 12 events |
| Treatment Group | Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Number of AEs | Total AEs | 79 events |
| Treatment Group | Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Number of AEs | Serious AEs or Deaths | 0 events |
Primary
Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Patient
Safety of adding the TLPLDC vaccine to SoC CPI monotherapy
Time frame: 12 months (1 year)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Patient | 12 participants |
Secondary
Tumor Response to Treatment Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
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.
Time frame: 12 months (1 year)
Population: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group | Tumor Response to Treatment Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | No Clinical Response | 2 Participants |
| Treatment Group | Tumor Response to Treatment Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Progressive Disease | 10 Participants |
| Treatment Group | Tumor Response to Treatment Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Stable Disease | 2 Participants |
| Treatment Group | Tumor Response to Treatment Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Not RECIST evaluable | 2 Participants |