Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study
BackgroundBVAC-C, a B cell– and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV–positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16– or...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1371353/full |
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| author | Chel Hun Choi Jeong-Won Lee Duk-Soo Bae Eun-Suk Kang Duck Cho Yong-Man Kim Kidong Kim Jae-Weon Kim Hee Seung Kim Young-Tae Kim Jung-Yun Lee Myong Cheol Lim Taegwon Oh Boyeong Song Insu Jeon Myunghwan Park Wu Hyun Kim Chang-Yuil Kang Byoung-Gie Kim |
| author_facet | Chel Hun Choi Jeong-Won Lee Duk-Soo Bae Eun-Suk Kang Duck Cho Yong-Man Kim Kidong Kim Jae-Weon Kim Hee Seung Kim Young-Tae Kim Jung-Yun Lee Myong Cheol Lim Taegwon Oh Boyeong Song Insu Jeon Myunghwan Park Wu Hyun Kim Chang-Yuil Kang Byoung-Gie Kim |
| author_sort | Chel Hun Choi |
| collection | DOAJ |
| description | BackgroundBVAC-C, a B cell– and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV–positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16– or 18–positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy.Patients and methodsPatients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsOf the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1–not reported), the median PFS was 5.8 months (95% CI 4.2–10.3), and the median OS was 17.7 months (95% CI 12.0–not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses.ConclusionBVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response.Clinical trial registrationClinicalTrials.gov, identifier NCT02866006. |
| first_indexed | 2024-04-24T17:35:47Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T17:35:47Z |
| publishDate | 2024-03-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-25f6fbb234fe45fb87de005ce22849a52024-03-28T04:39:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13713531371353Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa studyChel Hun Choi0Jeong-Won Lee1Duk-Soo Bae2Eun-Suk Kang3Duck Cho4Yong-Man Kim5Kidong Kim6Jae-Weon Kim7Hee Seung Kim8Young-Tae Kim9Jung-Yun Lee10Myong Cheol Lim11Taegwon Oh12Boyeong Song13Insu Jeon14Myunghwan Park15Wu Hyun Kim16Chang-Yuil Kang17Byoung-Gie Kim18Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Asan Medical Center, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of KoreaObstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of KoreaObstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of KoreaGraduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of KoreaCellid. Inc, Seoul, Republic of KoreaCellid. Inc, Seoul, Republic of KoreaCellid. Inc, Seoul, Republic of KoreaCellid. Inc, Seoul, Republic of KoreaCellid. Inc, Seoul, Republic of KoreaCellid. Inc, Seoul, Republic of KoreaDepartment of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaBackgroundBVAC-C, a B cell– and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV–positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16– or 18–positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy.Patients and methodsPatients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsOf the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1–not reported), the median PFS was 5.8 months (95% CI 4.2–10.3), and the median OS was 17.7 months (95% CI 12.0–not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses.ConclusionBVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response.Clinical trial registrationClinicalTrials.gov, identifier NCT02866006.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1371353/fullHPV 16HPV 18cervical cancerBVAC-Ctherapeutic vaccine |
| spellingShingle | Chel Hun Choi Jeong-Won Lee Duk-Soo Bae Eun-Suk Kang Duck Cho Yong-Man Kim Kidong Kim Jae-Weon Kim Hee Seung Kim Young-Tae Kim Jung-Yun Lee Myong Cheol Lim Taegwon Oh Boyeong Song Insu Jeon Myunghwan Park Wu Hyun Kim Chang-Yuil Kang Byoung-Gie Kim Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study Frontiers in Immunology HPV 16 HPV 18 cervical cancer BVAC-C therapeutic vaccine |
| title | Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study |
| title_full | Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study |
| title_fullStr | Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study |
| title_full_unstemmed | Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study |
| title_short | Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study |
| title_sort | efficacy and safety of bvac c in hpv type 16 or 18 positive cervical carcinoma who failed 1st platinum based chemotherapy a phase i iia study |
| topic | HPV 16 HPV 18 cervical cancer BVAC-C therapeutic vaccine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1371353/full |
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