Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.

Slingluff Craig L; Lewis Karl D; Robert Andtbacka; John Hyngstrom; Mohammed Milhem; Markovic Svetomir N; Tawnya Bowles; Omid Hamid; Leonel Hernandez-Aya; Joel Claveau; Sekwon Jang; Prejesh Philips; Holtan Shernan G; Shaheen Montaser F; Brendan Curti; William Schmidt; Butler Marcus O; Juan Paramo; Jose Lutzky; Arvinda Padmanabhan; Sajeve Thomas; Daniel Milton; Andrew Pecora; Takami Sato; Eddy Hsueh; Suprith Badarinath; John Keech; Sujith Kalmadi; Pallavi Kumar; Robert Weber; Edward Levine; Adam Berger; Anna Bar; Beck J Thaddeus; Travers Jeffrey B; Catalin Mihalcioiu; Brian Gastman; Peter Beitsch; Suthee Rapisuwon; John Glaspy; McCarron Edward C; Vinay Gupta; Deepti Behl; Brent Blumenstein; Peterkin Joanna J

Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.

Slingluff Craig L
, Lewis Karl D
, Robert Andtbacka
, John Hyngstrom
, Mohammed Milhem
, Markovic Svetomir N
, Tawnya Bowles
, Omid Hamid
, Leonel Hernandez-Aya
, Joel Claveau
, Sekwon Jang
, Prejesh Philips
, Holtan Shernan G
, Shaheen Montaser F
, Brendan Curti
, William Schmidt
, Butler Marcus O
, Juan Paramo
, Jose Lutzky
, Arvinda Padmanabhan

Sajeve Thomas, Daniel Milton, Andrew Pecora, Takami Sato, Eddy Hsueh, Suprith Badarinath, John Keech, Sujith Kalmadi, Pallavi Kumar, Robert Weber, Edward Levine, Adam Berger, Anna Bar, Beck J Thaddeus, Travers Jeffrey B, Catalin Mihalcioiu, Brian Gastman, Peter Beitsch, Suthee Rapisuwon, John Glaspy, McCarron Edward C, Vinay Gupta, Deepti Behl, Brent Blumenstein, Peterkin Joanna J

Research output: Contribution to journal › Article

Abstract

BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here.

METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients.

RESULTS: For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients(HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)).

CONCLUSIONS: Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas.

TRIAL REGISTRATION NUMBER: NCT01546571.

Original language	Undefined/Unknown
Journal	Articles, Abstracts, and Reports
State	Published - Oct 1 2021

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http://digitalcommons.psjhealth.org/publications/5350

Cite this

Craig L, S., Karl D, L., Andtbacka, R., Hyngstrom, J., Milhem, M., Svetomir N, M., Bowles, T., Hamid, O., Hernandez-Aya, L., Claveau, J., Jang, S., Philips, P., Shernan G, H., Montaser F, S., Curti, B., Schmidt, W., Marcus O, B., Paramo, J., Lutzky, J., ... Joanna J, P. (2021). Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence. Articles, Abstracts, and Reports. http://digitalcommons.psjhealth.org/publications/5350

@article{133ceca0a3a84ffabb21661dfd8b026f,

title = "Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.",

abstract = "BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80\%, target enrollment was 325 patients. RESULTS: For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95\% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95\% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95\% CI: 0.37 to 1.19), 0.72 (95\% CI: 0.35 to 1.50), and 1.19 (95\% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients(HR=0.324 (95\% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95\% CI: 0.255 to 0.952)). CONCLUSIONS: Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. TRIAL REGISTRATION NUMBER: NCT01546571.",

author = "\{Craig L\}, Slingluff and \{Karl D\}, Lewis and Robert Andtbacka and John Hyngstrom and Mohammed Milhem and \{Svetomir N\}, Markovic and Tawnya Bowles and Omid Hamid and Leonel Hernandez-Aya and Joel Claveau and Sekwon Jang and Prejesh Philips and \{Shernan G\}, Holtan and \{Montaser F\}, Shaheen and Brendan Curti and William Schmidt and \{Marcus O\}, Butler and Juan Paramo and Jose Lutzky and Arvinda Padmanabhan and Sajeve Thomas and Daniel Milton and Andrew Pecora and Takami Sato and Eddy Hsueh and Suprith Badarinath and John Keech and Sujith Kalmadi and Pallavi Kumar and Robert Weber and Edward Levine and Adam Berger and Anna Bar and \{J Thaddeus\}, Beck and \{Jeffrey B\}, Travers and Catalin Mihalcioiu and Brian Gastman and Peter Beitsch and Suthee Rapisuwon and John Glaspy and \{Edward C\}, McCarron and Vinay Gupta and Deepti Behl and Brent Blumenstein and \{Joanna J\}, Peterkin",

year = "2021",

month = oct,

day = "1",

language = "Undefined/Unknown",

journal = "Articles, Abstracts, and Reports",

}

Craig L, S, Karl D, L, Andtbacka, R, Hyngstrom, J, Milhem, M, Svetomir N, M, Bowles, T, Hamid, O, Hernandez-Aya, L, Claveau, J, Jang, S, Philips, P, Shernan G, H, Montaser F, S, Curti, B, Schmidt, W, Marcus O, B, Paramo, J, Lutzky, J, Padmanabhan, A, Thomas, S, Milton, D, Pecora, A, Sato, T, Hsueh, E, Badarinath, S, Keech, J, Kalmadi, S, Kumar, P, Weber, R, Levine, E, Berger, A, Bar, A, J Thaddeus, B, Jeffrey B, T, Mihalcioiu, C, Gastman, B, Beitsch, P, Rapisuwon, S, Glaspy, J, Edward C, M, Gupta, V, Behl, D, Blumenstein, B & Joanna J, P 2021, 'Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.', Articles, Abstracts, and Reports. <http://digitalcommons.psjhealth.org/publications/5350>

TY - JOUR

T1 - Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.

AU - Craig L, Slingluff

AU - Karl D, Lewis

AU - Andtbacka, Robert

AU - Hyngstrom, John

AU - Milhem, Mohammed

AU - Svetomir N, Markovic

AU - Bowles, Tawnya

AU - Hamid, Omid

AU - Hernandez-Aya, Leonel

AU - Claveau, Joel

AU - Jang, Sekwon

AU - Philips, Prejesh

AU - Shernan G, Holtan

AU - Montaser F, Shaheen

AU - Curti, Brendan

AU - Schmidt, William

AU - Marcus O, Butler

AU - Paramo, Juan

AU - Lutzky, Jose

AU - Padmanabhan, Arvinda

AU - Thomas, Sajeve

AU - Milton, Daniel

AU - Pecora, Andrew

AU - Sato, Takami

AU - Hsueh, Eddy

AU - Badarinath, Suprith

AU - Keech, John

AU - Kalmadi, Sujith

AU - Kumar, Pallavi

AU - Weber, Robert

AU - Levine, Edward

AU - Berger, Adam

AU - Bar, Anna

AU - J Thaddeus, Beck

AU - Jeffrey B, Travers

AU - Mihalcioiu, Catalin

AU - Gastman, Brian

AU - Beitsch, Peter

AU - Rapisuwon, Suthee

AU - Glaspy, John

AU - Edward C, McCarron

AU - Gupta, Vinay

AU - Behl, Deepti

AU - Blumenstein, Brent

AU - Joanna J, Peterkin

PY - 2021/10/1

Y1 - 2021/10/1

N2 - BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. RESULTS: For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients(HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). CONCLUSIONS: Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. TRIAL REGISTRATION NUMBER: NCT01546571.

AB - BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. RESULTS: For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients(HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). CONCLUSIONS: Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. TRIAL REGISTRATION NUMBER: NCT01546571.

M3 - Article

JO - Articles, Abstracts, and Reports

JF - Articles, Abstracts, and Reports

ER -