On May 13, 2020 Polynoma LLC, a U.S. immuno-oncology focused biopharmaceutical company and wholly-owned subsidiary of Hong Kong-listed CK Life Sciences Int’l., (Holdings) Inc., reported final analysis of clinical data from Part B1 of MAVIS (Melanoma Antigen Vaccine Immunotherapy Study), a Phase III study of seviprotimut-L, an investigational melanoma vaccine candidate, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program, to be held online May 29-31, 2020 (Press release, Polynoma, MAY 13, 2020, View Source [SID1234557952]). The study abstract is one of 12 abstracts selected for discussion in the Melanoma/Skin Cancers poster discussion session.
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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 (AJCC) Stage IIB/C, IIIA, IIIB/C melanoma at high risk of recurrence after definitive surgical resection.
Highlights of the data presented include:
Improved outcomes in Stage IIB/C patients: Final analysis of subgroups confirmed the findings from the interim analysis, suggesting enhanced RFS for seviprotimut-L in patients with AJCC Stage IIB/IIC melanoma, particularly those under age 60, and those with ulceration, whose lesions are considered more serious because they have a greater risk of metastasis.1
Early evidence of survival benefit in Stage IIB/C patients: For Stage IIB/IIC melanoma patients under 60, there was a trend toward improved overall survival for those treated with seviprotimut-L.
Favorable adverse event profile: Seviprotimut-L was well-tolerated with treatment-emergent adverse events (AEs) similar to patients given placebo. There were no treatment-related serious adverse events.
Melanoma is the most diagnosed cancer among 25 to 29 year-olds in the United States, and passage from Stage II to Stage III melanoma marks a critical therapeutic intervention point to improve survival. 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 (22.5%) for metastatic Stage IV.2
"The final analysis of this part of the study reinforces the findings from our interim analysis last year, suggesting improved outcomes with seviprotimut-L in Stage IIB/IIC melanoma patients, particularly in those aged under 60. Furthermore, the latest findings extend the benefit to include disease with ulceration," said Melvin Toh, Chief Technology Officer at Polynoma and Vice President & Chief Scientific Officer at CK Life Sciences. "With a median patient follow-up of more than 48 months, the data show a durable RFS clinical benefit of seviprotimut-L in Stage IIB/IIC melanoma. We believe seviprotimut-L will be an important new option for the adjuvant treatment of patients with localized melanoma and look forward to advancing seviprotimut-L into the definitive part of the MAVIS Study."
"These data show promise for seviprotimut-L as a vaccine-based treatment of melanoma," said Craig L. Slingluff Jr., MD, 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 findings support moving forward with a pivotal trial testing seviprotimut-L as an adjuvant treatment for patients with Stage IIB/C melanoma, with stratification by age."
FURTHER DETAILS ON POSTER PRESENTATION AND DISCUSSION SESSION:
Abstract 10017: Final analysis of relapse-free survival in a multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine after resection of high-risk melanoma.
Poster: 366
Authors: Craig L. Slingluff, Jr., MD; Brent A. Blumenstein, PhD; Karl D. Lewis, MD; Robert H. Andtbacka, MD, CM, FACS, FRCSC; John Hyngstrom, MD; Mohammed Milhem, MBBS; Svetomir N. Markovic, MD, PhD; Omid Hamid, MD; Leonel Hernandez-Aya, MD PhD; Tawnya L. Bowles, MD; Prejesh Philips, MD; Sekwon Jang, MD; Jose Lutzky, MD, FACP; Anna Bar, MD; Peter D. Beitsch, MD
Poster Discussion Session
Session Title: Melanoma/Skin Cancers
Presentation Title: Adjuvant/Neoadjuvant Approaches
Discussant: Kenneth F. Grossmann, MD, PhD | Huntsman Cancer Institute, University of Utah
Poster and Discussion: will be available "on demand" on the ASCO (Free ASCO Whitepaper) website starting May 29 at 8:00 am EDT
The data being 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 toward benefit (Hazard Ratio "HR" = 0.88). Subgroup analysis based on planned stratification revealed the HR for the Stage IIB/IIC subset to be 0.65 (number of patients, "N" =111, 95% CI [0.37, 1.17]), favoring seviprotimut-L.
Age has been identified as a cause of decreased immune competence;3 thus, outcomes were assessed as a function of age as an effect modifier. Final efficacy analysis of subgroups confirmed treatment with seviprotimut-L enhanced RFS for patients less than 60 years overall (N=191, HR=0.64, 95% CI [0.38, 1.08]) and among Stage IIB/IIC melanoma patients (N=52, HR=0.32, 95% CI [0.12, 0.86]).
Furthermore, in a multivariable RFS model, for Stage IIB/IIC patients less than 60 years with ulceration, the HR was 0.209 (N=38, 95% CI [0.07,0.61]). For OS, for patients less than 60, HR = 0.41 [0.33,1.14] (n=191, 19 deaths) and for those ≥60, HR = 0.92 [0.39,2.12] (n = 156, 24 deaths).
In the study, seviprotimut-L was well-tolerated with treatment-emergent adverse events (AEs) similar to placebo patients. There were no treatment-related serious adverse events (SAEs) 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.
About MAVIS
MAVIS (Melanoma Antigen Vaccine Immunotherapy Study) 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 melanoma at high risk of recurrence after definitive surgical resection. MAVIS is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA. For additional information about the trial, please visit View Source
About Seviprotimut-L
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.