The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up

Diane M. Harper, Pekka Nieminen, Gilbert Donders, Mark H. Einstein, Francisco A Garcia, Warner K. Huh, Mark H. Stoler, Katerina Glavini, Gemma Attley, Jean Marc Limacher, Berangere Bastien, Elizabeth Calleja

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types. Methods: Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug. Results: Of the 129 women randomized to vaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24% vs. 10%, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21% vs. 0%, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions. Conclusions: The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.

Original languageEnglish (US)
JournalGynecologic oncology
DOIs
StatePublished - Jan 1 2019

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Papillomavirus Vaccines
Cervical Intraepithelial Neoplasia
Vaccines
Safety
Placebos
Therapeutics
Papillomavirus Infections
Viral DNA
Pharmaceutical Preparations
Cell Biology
Vaccination
Injections
Population

Keywords

  • Cervical cancer
  • CIN 2/3
  • HPV
  • Immunotherapy
  • Therapeutic vaccine
  • Women

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3 : Randomized controlled phase II trial with 2.5 years of follow-up. / Harper, Diane M.; Nieminen, Pekka; Donders, Gilbert; Einstein, Mark H.; Garcia, Francisco A; Huh, Warner K.; Stoler, Mark H.; Glavini, Katerina; Attley, Gemma; Limacher, Jean Marc; Bastien, Berangere; Calleja, Elizabeth.

In: Gynecologic oncology, 01.01.2019.

Research output: Contribution to journalArticle

Harper, Diane M. ; Nieminen, Pekka ; Donders, Gilbert ; Einstein, Mark H. ; Garcia, Francisco A ; Huh, Warner K. ; Stoler, Mark H. ; Glavini, Katerina ; Attley, Gemma ; Limacher, Jean Marc ; Bastien, Berangere ; Calleja, Elizabeth. / The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3 : Randomized controlled phase II trial with 2.5 years of follow-up. In: Gynecologic oncology. 2019.
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abstract = "Background: While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types. Methods: Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug. Results: Of the 129 women randomized to vaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24{\%} vs. 10{\%}, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21{\%} vs. 0{\%}, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions. Conclusions: The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.",
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T1 - The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3

T2 - Randomized controlled phase II trial with 2.5 years of follow-up

AU - Harper, Diane M.

AU - Nieminen, Pekka

AU - Donders, Gilbert

AU - Einstein, Mark H.

AU - Garcia, Francisco A

AU - Huh, Warner K.

AU - Stoler, Mark H.

AU - Glavini, Katerina

AU - Attley, Gemma

AU - Limacher, Jean Marc

AU - Bastien, Berangere

AU - Calleja, Elizabeth

PY - 2019/1/1

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N2 - Background: While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types. Methods: Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug. Results: Of the 129 women randomized to vaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24% vs. 10%, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21% vs. 0%, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions. Conclusions: The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.

AB - Background: While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types. Methods: Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug. Results: Of the 129 women randomized to vaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24% vs. 10%, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21% vs. 0%, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions. Conclusions: The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.

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KW - Immunotherapy

KW - Therapeutic vaccine

KW - Women

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