Phase IIB TL + YCWP + DC in Melanoma

The majority of melanoma vaccines tested to date have been antigen-specific vaccines targeting melanoma-specific or associated antigens and utilizing a variety of delivery systems and immune-adjuvants. As opposed to testing an "off the shelf" vaccine that might be able to treat a subset of patients, our approach has been personalized to the patient and applicable to all patients. Our vaccine approach consists of harnessing the most potent antigen presenting cell in the body - the dendritic cell (DC) - together with the full repertoire of tumor antigens from an individual's cancer. We have conducted phase I and II studies using an autologous DC-tumor cell fusion technique that has now been simplified into a DC-tumor cell lysate vaccine. The autologous tumor lysate (TL) is loaded into yeast cell wall particles (YCWP) that are naturally and efficiently taken up into the patient's DC. These autologous tumor lysate, particle-loaded, DC (TLPLDC) are injected intradermally (ID) monthly x 3 followed by boosters at 6, 12, and 18 months.

Sex

All

Minimum age

18 Years

Maximum age

99 Years

Inclusion Criteria:

* 18 years or older
* Eastern Cooperative Oncology Group (ECOG) performance status 0,1 (Appendix D)
* AJCC stage III or IV completely resectable melanoma identified before surgery
* Approximately 1 mg (1 cm3) of accessible and dispensable tumor that will not interfere with pathologic staging
* Clinically disease-free after surgery
* Completing SoC adjuvant therapy per NCCN guidelines to include chemotherapy, radiation therapy, and/or biologic therapy as clinically indicated. (Consent #2 should be signed as close to completion of SoC as possible but may overlap completion by up to one month.)
* Vaccinations initiated between 3 weeks and 3 months from completion of SoC multi-modality cancer care
* 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%
* 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)
* Signed informed consent

Exclusion Criteria:

* Evidence of residual disease after surgery and SoC adjuvant therapies
* Insufficient tumor available to produce vaccine
* ECOG \>2 performance status (Appendix D)
* Immune deficiency disease or known history of HIV, HBV, HCV
* Receiving immunosuppressive therapy including chronic steroids, 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)

• DERIVEDVan Decar SG, Carpenter EL, Adams AM, Chick RC, Clifton GT, Stojadinovic A, Vreeland TJ, Valdera FA, Tiwari A, O'Shea AE, McCarthy PM, Hale DF, Bohan PMK, Hickerson AT, Cindass JL, Hyngstrom J, Berger AC, Jakub JW, Sussman JJ, Shaheen M, Yu X, Wagner T, Faries MB, Peoples GE. Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial. Cancer Treat Res Commun. 2024;41:100843. doi: 10.1016/j.ctarc.2024.100843. Epub 2024 Sep 11. PMID 39305541
• DERIVEDCarpenter EL, Van Decar S, Adams AM, O'Shea AE, McCarthy P, Chick RC, Clifton GT, Vreeland T, Valdera FA, Tiwari A, Hale D, Kemp Bohan P, Hickerson A, Smolinsky T, Thomas K, Cindass J, Hyngstrom J, Berger AC, Jakub J, Sussman JJ, Shaheen MF, Yu X, Wagner TE, Faries M, Peoples GE. Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III/IV melanoma: a prespecified 36-month analysis. J Immunother Cancer. 2023 Aug;11(8):e006665. doi: 10.1136/jitc-2023-006665. PMID 37536936
• DERIVEDVreeland TJ, Clifton GT, Hale DF, Chick RC, Hickerson AT, Cindass JL, Adams AM, Bohan PMK, Andtbacka RHI, Berger AC, Jakub JW, Sussman JJ, Terando AM, Wagner T, Peoples GE, Faries MB. A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis. Ann Surg Oncol. 2021 Oct;28(11):6126-6137. doi: 10.1245/s10434-021-09709-1. Epub 2021 Feb 27. PMID 33641012