Potential Treatment Option for Cancer Patients With Localized Melanoma

Polynoma seviprotimut-L is an investigational melanoma vaccine candidate 
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(Vax Before Cancer)

An innovative San Diego based biopharmaceutical company is scheduled to present clinical data from the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS), a Phase III clinical study of seviprotimut-L, which is a melanoma vaccine candidate.

On November 8, 2019, at the 2019 Society for Immunotherapy of Cancer meeting, the following study highlights will be presented:

  • Improved outcomes in Stage IIB/C patients: Interim analysis of subgroups suggested enhanced RFS for seviprotimut-L among those with AJCC stage IIB/IIC melanoma, as well as those under age 60.
  • Favorable adverse event profile: Seviprotimut-L was well-tolerated with treatment-emergent adverse events (AEs) similar to patients given placebo.

The preliminary data from MAVIS also suggest that seviprotimut-L could serve as a breakthrough in the vaccine-based treatment of melanoma, where to date, no other vaccine has proven successful, said Polynoma LLC in a press release on November 6, 2019.

This announcement is good news since melanoma is the least common, but the most fatal skin cancer, accounting for only about 1 percent of all cases, but the vast majority of skin cancer fatalities.

Melanoma is the third most common cancer among women ages 20-39 and the second most common cancer in men ages 20-39.

In 2019, it is estimated that there will be 96,480 new cases of melanoma in the USA and 7,230 related fatalities.

MAVIS is a multicenter, double-blind, placebo-controlled adaptive Phase III trial to assess the safety and efficacy of seviprotimut-L, with primary endpoints of recurrence-free survival (RFS) and overall survival (OS) in patients with American Joint Committee on Cancer Stage IIB/C, IIIA, IIIB/C melanoma at high risk of recurrence after definitive surgical resection.

Treatment of Stage IIB/IIC melanoma is primarily limited to surgery, coupled with a "wait and see" approach. 

However, recurrence of the disease can occur following definitive resection of the melanoma. Many patients progress to more advanced stages following resection and 5-year survival rates fall sharply after a patient passes from localized Stage II melanoma into regional Stage III disease (98.4% to 63.6%). 

Five-year survival rates are distinctly lower (22.4%) for metastatic Stage IV.

"The passage from Stage II to Stage III melanoma marks a critical point in time where survival is severely threatened. We find this initial data from MAVIS to be extremely encouraging and validating," said Melvin Toh, Chief Technology Officer at Polynoma.

"With promising evidence of efficacy and safety as seen in this analysis, seviprotimut-L has the potential to be an important new option for the adjuvant treatment of patients with localized melanoma."

"The data show that vaccines are a potentially important new class of immunotherapy for the treatment of stage IIB/IIC melanoma, after surgery," said Craig L. Slingluff Jr., M.D., Professor of Surgery and Director of the Human Immune Therapy Center and co-leader of the Cancer Therapeutics Program of the UVA Cancer Center. 

"These promising efficacy and safety data support continuing the study of seviprotimut-L in melanoma, particularly in Stage IIB/C patients and those under the age of sixty."

The data presented assessed the treatment effects of seviprotimut-L in patients with AJCCv7 stage IIB-III cutaneous melanoma after surgical resection. 347 patients ages 18-75, ECOG PS 0-1, were enrolled and randomized 2:1 to seviprotimut-L 40 mcg or placebo, administered intradermally every 2 weeks x 5, then monthly x 4, then every 3 months to month 24. Patients were stratified by stage (IIB/C, IIIA, IIIB/C).

By intent-to-treat (ITT) analysis, RFS was not significantly enhanced for seviprotimut-L in the full study population but trended slightly higher. However, interim efficacy analysis of subgroups based on pre-planned stratification suggested enhanced RFS for seviprotimut-L among Stage IIB/IIC melanoma patients (Hazard Ratio= 0.59, 95% CI [0.33,1.07]).

Age has been identified as a cause of decreased immune competence; thus, outcomes were assessed as a function of age as an effect modifier. 

Effects estimates for patients aged less than 60 years are favorable to seviprotimut-L in the overall population (Hazard Ratio= 0.61, 95% CI [0.36, 1.05]) and in the Stage IIB/IIC population (Hazard Ratio= 0.239, 95% CI [0.083, 0.69]). 

In the study, seviprotimut-L was well-tolerated with treatment-emergent adverse events (AEs) similar to placebo patients. 

There were no serious adverse events or Grade 4 or 5 adverse events in the 347 patients studied, and the vast majority of events were Grade 1-2 injection site reactions that were managed by topical cream/s or an over-the-counter antihistamine. 

Seviprotimut-L is an allogeneic, polyvalent, partially purified shed melanoma antigen vaccine derived from three proprietary human melanoma cell lines. Seviprotimut-L stimulates humoral and cellular immune responses. Melanoma-associated antigens (MAAs) found in seviprotimut-L are taken up by antigen-presenting cells (e.g., dendritic cells) which then activate the production of antigen-specific cytotoxic T-lymphocytes (CTLs) as well as develop antibody responses against MAAs. 

These CTLs and antibodies then recognize and act on tumor cells expressing the MAAs on their surfaces, causing cell death. Seviprotimut-L is currently in development for the adjuvant treatment of patients with Stages IIB to IIIC melanoma, following definitive resection.

Polynoma LLC is a U.S. immuno-oncology focused biopharmaceutical company headquartered in San Diego, California.

Melanoma Cancer news is published by Vax-Before-Cancer