TY - JOUR
T1 - Vvax001, a Therapeutic Vaccine, for Patients with HPV16-Positive High-grade Cervical Intraepithelial Neoplasia
T2 - A Phase II Trial
AU - Eerkens, Anneke L
AU - Esajas, Martha D
AU - Brummel, Koen
AU - Vledder, Annegé
AU - van Rooij, Nienke
AU - Plat, Annechien
AU - Avalos Haro, Stefany B
AU - Paijens, Sterre T
AU - Slagter-Menkema, Lorian
AU - Schuuring, Ed
AU - Werner, Naomi
AU - Kosterink, Jos G W
AU - Kroesen, Bart-Jan
AU - Wilschut, Jan C
AU - Daemen, Toos
AU - Bart, Joost
AU - Nijman, Hans W
AU - de Bruyn, Marco
AU - Yigit, Refika
N1 - Publisher Copyright:
©2025 American Association for Cancer Research.
PY - 2025/3/17
Y1 - 2025/3/17
N2 - PURPOSE: Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus (SFV) vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. Here, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3).PATIENTS AND METHODS: Patients with newly diagnosed HPV16-positive CIN3 were eligible for participation. Patients received 3 immunizations of Vvax001 (5x107 infectious particles) at a three-week interval. Up to 19 weeks after the last immunization patients were monitored for regression of CIN3 by colposcopy. A colposcopy-guided biopsy was taken at the last visit and a standard of care loop excision was performed only in case of remaining CIN2/3. Histopathologic response rates, HPV16 clearance, treatment-related adverse events (trAEs), and vaccine-induced immune responses were assessed.RESULTS: A total of 18 patients were enrolled and fully immunized. Colposcopic examination revealed a reduction in CIN3 lesion sizes in 17/18 patients (94%) already evident from 3 weeks onwards after the last immunization. A histopathological complete response (regression to CIN1 or no dysplasia) was observed in 9/18 patients (50%), and HPV16 clearance in 10/16 patients (63%). Vvax001 did not induce clearance of other HPV types. To date, no recurrences have been observed, with a median and longest disease-free survival of 20 and 30 months, respectively. No serious AEs were observed.CONCLUSIONS: Treatment with Vvax001 is safe, feasible, and shows preliminary clinical effectiveness in patients with HPV16-associated CIN3 lesions.
AB - PURPOSE: Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus (SFV) vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 and -E7 cytotoxic T-cell responses. Here, we investigated the clinical efficacy of Vvax001 in patients with HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3).PATIENTS AND METHODS: Patients with newly diagnosed HPV16-positive CIN3 were eligible for participation. Patients received 3 immunizations of Vvax001 (5x107 infectious particles) at a three-week interval. Up to 19 weeks after the last immunization patients were monitored for regression of CIN3 by colposcopy. A colposcopy-guided biopsy was taken at the last visit and a standard of care loop excision was performed only in case of remaining CIN2/3. Histopathologic response rates, HPV16 clearance, treatment-related adverse events (trAEs), and vaccine-induced immune responses were assessed.RESULTS: A total of 18 patients were enrolled and fully immunized. Colposcopic examination revealed a reduction in CIN3 lesion sizes in 17/18 patients (94%) already evident from 3 weeks onwards after the last immunization. A histopathological complete response (regression to CIN1 or no dysplasia) was observed in 9/18 patients (50%), and HPV16 clearance in 10/16 patients (63%). Vvax001 did not induce clearance of other HPV types. To date, no recurrences have been observed, with a median and longest disease-free survival of 20 and 30 months, respectively. No serious AEs were observed.CONCLUSIONS: Treatment with Vvax001 is safe, feasible, and shows preliminary clinical effectiveness in patients with HPV16-associated CIN3 lesions.
UR - http://www.scopus.com/inward/record.url?scp=105001220150&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-24-1662
DO - 10.1158/1078-0432.CCR-24-1662
M3 - Article
C2 - 39849926
SN - 1078-0432
VL - 31
SP - 1016
EP - 1026
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 6
ER -