Seviprotimut-L

Seviprotimut-L (POL-103A) is a novel melanoma vaccine designed to stimulate the body’s immune system to fight tumor cells using shed antigens from 3 proprietary melanoma cell lines. Antigens are rapidly released from the cancer cells, then purified and processed before administration to patients.8

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The international, double-blind, placebo-controlled, phase 3 MAVIS trial enrolled 1059 patients to evaluate the safety and efficacy of the immunotherapy in resected stage 2b, 2c, or 3 melanoma. Patients were randomly assigned 2:1 to receive the vaccine intradermally as 4 injections or placebo. Final data collection for the primary outcome measure of recurrence-free survival is estimated to be completed in July 2016.

The MAVIS trial was initiated based on the findings of 2 randomized, placebo-controlled, phase 2 trials with a small number of patients that demonstrated favorable efficacy with regard to prolonged recurrence-free and overall survival, as well as an excellent safety profile.9

Coxsackievirus A21 (CVA21)

CVA21 is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21. It is a naturally occurring, genetically unaltered virus that is being evaluated in a number of cancer types, including late stage melanoma.10

The multicenter, open-label, phase 2 CALM study demonstrated promising activity with the immunotherapeutic agent in the treatment of stage 3C-4M1c melanoma. Results showed that immune-related progression-free survival at 6 months was 38.6% with a median progression-free survival of 4.2 months. The overall response rate was 28.1% with 6 or more months of durable response in 19.3% of 57 evaluable patients.

The most common adverse events were grade 1 fatigue, chills, local injection site reactions, and fever. No grade 3 or 4 treatment-related adverse events were reported.

For the study, 57 patients with treated or untreated unresectable late stage melanoma received intralesional injections of CVA21 on days 1, 3, 5, 8, and 22, and then every 3 weeks for 6 additional injections. Those who displayed immune-related progression-free survival or better at 6 months could receive 9 more injections.

“CVA21 can also be given intravenously,” Dr Sullivan noted. “This may set it apart from T-VEC (talimogene laherparepvec).”

“Vaccines in general have been a major challenge in melanoma, but a lot of these newer immunotherapies may offer something that the old vaccine could not, which is that they stimulate the immune system much better,” Dr Sullivan explained. “Whether or not they lead to more widespread antigen recognition and tumor immunity may remain to be seen.”

Reference

  1. What are the key statistics about melanoma skin cancer? American Cancer Society web site. February 1, 2016. http://www.cancer.org/cancer/skincancer-melanoma/detailedguide/melanoma-skin-cancer-key-statistics. Accessed March 21, 2016.
  2. NCCN Clinical Practice Guidelines in Oncology™. Melanoma. Version 2.2016. Available at: http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Accessed March 21, 2016.
  3. Array BioPharma announces phase 3 binimetinib trial meets primary endpoint for NRAS-mutant melanoma [news release]. Boulder, CO: Array BioPharma; December 16, 2015. http://investor.arraybiopharma.com/phoenix.zhtml?c=123810&p=irol-newsArticle&ID=2122959. Accessed March 22, 2016.
  4. Sullivan RJ, Weber JS, Patel SP, et al. A phase Ib/II study of BRAF inhibitor (BRAFi) encorafenib (ENCO) plus MEK inhibitor (MEKi) binimetinib (BINI) in cutaneous melanoma patients naive to BRAFi treatment. J Clin Oncol. 2015;33(suppl; abstr 9007).
  5. Hamid O, Patel M, Hodi S, et al. Preliminary clinical safety, tolerability and activity of atezolizumab (anti-PDL1) combined with vemurafenib in BRAF V600 metastatic melanoma. Pigment Cell Melanoma Res. 2015;28(6):753-826.
  6. Ribas A, Butler M, Lutzky J, et al. Phase I study combining anti-PD-L1 (MEDI4736) with BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in advanced melanoma. J Clin Oncol. 2015;33(suppl; abstr 3003).
  7. Dillman RO, Bayer ME, Langford JA, et al. Phase III multicenter trial of eltrapuldencel-T: autologous dendritic cells loaded with irradiated autologous tumor cells (DC-TC) in granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with metastatic melanoma (INTUS trial). J Clin Oncol. 2015;33(suppl abstr TPS9082).
  8. Polynoma commences phase III melanoma vaccine clinical trial [news release]. San Diego, CA: Polynoma; June 4, 2012. http://polynoma.com/wp-content/uploads/2012/02/PolynomaCommencesPhaseIIIMelanomaVaccineClinicalTrial.pdf. Accessed March 23, 2016.
  9. Bystryn JC, Zeleniuch-Jacquotte A, Oratz R, et al. Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine. Clin Cancer Res. 2001;7(7):1882-1887.
  10. Andtbacka RHI, Curti BD, Kaufman H, et al. Final data from CALM: a phase II study of Coxsackievirus A21 (CVA21) oncolytic virus immunotherapy in patients with advanced melanoma. J Clin Oncol. 2015;33(suppl; abstr 9030).

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Melanoma Skin Cancer