Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study

Warner K. Huh; William E. Brady; Paula M. Fracasso; Don S. Dizon; Matthew A. Powell; Bradley J. Monk; Charles A. Leath; Lisa M. Landrum; Edward J. Tanner; Erin K. Crane; Stefanie Ueda; Michael T. McHale; Carol Aghajanian

doi:10.1016/j.ygyno.2020.06.493

Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study

Warner K. Huh^*, William E. Brady, Paula M. Fracasso, Don S. Dizon, Matthew A. Powell, Bradley J. Monk, Charles A. Leath, Lisa M. Landrum, Edward J. Tanner, Erin K. Crane, Stefanie Ueda, Michael T. McHale, Carol Aghajanian

^*Corresponding author for this work

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Objective: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). Methods: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 10⁹ colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). Results: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3–12.1) and median PFS was 2.8 months (95% CI: 2.6–3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. Conclusion: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.

Original language	English (US)
Pages (from-to)	562-569
Number of pages	8
Journal	Gynecologic oncology
Volume	158
Issue number	3
DOIs	https://doi.org/10.1016/j.ygyno.2020.06.493
State	Published - Sep 2020

Funding

Dr. William Brady's institution received grant funding from the NCI . He received support for travel to meetings for the study or other purposes from Advaxis. He also received money paid to him from Sarah Cannon Development Innovations. Dr. Carol Aghajanian reports personal fees from Tesaro, personal fees from Immunogen, grants and personal fees from Clovis , personal fees from Mateon Therapeutics, grants from Genentech , grants from AbbVie , grants from AstraZeneca , personal fees from Eisai/Merck, outside the submitted work. Dr. Charles Leath's institute received grant money from the NIH . His institution also received grants/grants pending for contracted research for recurrent cervical cancer from Agenus . This study was supported by National Institute of Health grants to NRG Oncology ( 1U10 CA180822 ) and NRG Operations ( U10CA180868 ). Dr. William Brady's institution received grant funding from the NCI. He received support for travel to meetings for the study or other purposes from Advaxis. He also received money paid to him from Sarah Cannon Development Innovations.Dr. Don Dizon received monies for consultancy from Clovis, Regeneron and AstraZeneca. His institution received grants/pending grants from Bristol Myers Squibb, Kazia, Tesaro and Lilly.Dr. Bradley Monk's institution received Grant money from Advasix and Genentech. He received money from Advaxis, Genentech and Genmab for consulting free or honorarium. He received fee for participation in review activities such as data monitoring boards, statistical analysis, end point committees and the like from Advaxis. Dr. Monk also received money paid to him for consultancy from Advaxis, Genentech and Genmab. His institution has grants/grants pending from Advaxis, Genentech and Genmab. He received payment for lectures, including service on speakers bureaus from Genentech as well as payment for development of educational presentations. He also has received money from Advaxis for stock/stock options.Dr. Charles Leath's institute received grant money from the NIH. His institution also received grants/grants pending for contracted research for recurrent cervical cancer from Agenus.Dr. Carol Aghajanian reports personal fees from Tesaro, personal fees from Immunogen, grants and personal fees from Clovis, personal fees from Mateon Therapeutics, grants from Genentech, grants from AbbVie, grants from AstraZeneca, personal fees from Eisai/Merck, outside the submitted work.This study was supported by National Institute of Health grants to NRG Oncology (1U10 CA180822) and NRG Operations (U10CA180868). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Alabama at Birmingham, Washington University School of Medicine, University of Oklahoma Health Sciences Center, Carolinas Medical Center/Levine Cancer Institute, UC San Diego Moores Cancer Center, UCSF-Mount Zion, Johns Hopkins University/Sidney Kimmel Cancer Center, Stony Brook University Medical Center, Saint Joseph's Hospital and Medical Center, University of Michigan Health System-Cancer Center, Sinai Hospital of Baltimore, University of Texas Medical Branch and the University of Virginia. Dr. Don Dizon received monies for consultancy from Clovis, Regeneron and AstraZeneca. His institution received grants/pending grants from Bristol Myers Squibb , Kazia , Tesaro and Lilly .

Keywords

HPV
Immunotherapy
Listeria
Metastatic
Recurrent cervical cancer

ASJC Scopus subject areas

Obstetrics and Gynecology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ygyno.2020.06.493

Cite this

Huh, W. K., Brady, W. E., Fracasso, P. M., Dizon, D. S., Powell, M. A., Monk, B. J., Leath, C. A., Landrum, L. M., Tanner, E. J., Crane, E. K., Ueda, S., McHale, M. T., & Aghajanian, C. (2020). Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study. Gynecologic oncology, 158(3), 562-569. https://doi.org/10.1016/j.ygyno.2020.06.493

@article{8fe4b364ef4e43f39a279f4fa7d02497,

title = "Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study",

abstract = "Objective: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). Methods: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). Results: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3–12.1) and median PFS was 2.8 months (95% CI: 2.6–3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. Conclusion: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.",

keywords = "HPV, Immunotherapy, Listeria, Metastatic, Recurrent cervical cancer",

author = "Huh, {Warner K.} and Brady, {William E.} and Fracasso, {Paula M.} and Dizon, {Don S.} and Powell, {Matthew A.} and Monk, {Bradley J.} and Leath, {Charles A.} and Landrum, {Lisa M.} and Tanner, {Edward J.} and Crane, {Erin K.} and Stefanie Ueda and McHale, {Michael T.} and Carol Aghajanian",

note = "Funding Information: Dr. William Brady's institution received grant funding from the NCI . He received support for travel to meetings for the study or other purposes from Advaxis. He also received money paid to him from Sarah Cannon Development Innovations. Funding Information: Dr. Carol Aghajanian reports personal fees from Tesaro, personal fees from Immunogen, grants and personal fees from Clovis , personal fees from Mateon Therapeutics, grants from Genentech , grants from AbbVie , grants from AstraZeneca , personal fees from Eisai/Merck, outside the submitted work. Funding Information: Dr. Charles Leath's institute received grant money from the NIH . His institution also received grants/grants pending for contracted research for recurrent cervical cancer from Agenus . Funding Information: This study was supported by National Institute of Health grants to NRG Oncology ( 1U10 CA180822 ) and NRG Operations ( U10CA180868 ). Funding Information: Dr. William Brady's institution received grant funding from the NCI. He received support for travel to meetings for the study or other purposes from Advaxis. He also received money paid to him from Sarah Cannon Development Innovations.Dr. Don Dizon received monies for consultancy from Clovis, Regeneron and AstraZeneca. His institution received grants/pending grants from Bristol Myers Squibb, Kazia, Tesaro and Lilly.Dr. Bradley Monk's institution received Grant money from Advasix and Genentech. He received money from Advaxis, Genentech and Genmab for consulting free or honorarium. He received fee for participation in review activities such as data monitoring boards, statistical analysis, end point committees and the like from Advaxis. Dr. Monk also received money paid to him for consultancy from Advaxis, Genentech and Genmab. His institution has grants/grants pending from Advaxis, Genentech and Genmab. He received payment for lectures, including service on speakers bureaus from Genentech as well as payment for development of educational presentations. He also has received money from Advaxis for stock/stock options.Dr. Charles Leath's institute received grant money from the NIH. His institution also received grants/grants pending for contracted research for recurrent cervical cancer from Agenus.Dr. Carol Aghajanian reports personal fees from Tesaro, personal fees from Immunogen, grants and personal fees from Clovis, personal fees from Mateon Therapeutics, grants from Genentech, grants from AbbVie, grants from AstraZeneca, personal fees from Eisai/Merck, outside the submitted work.This study was supported by National Institute of Health grants to NRG Oncology (1U10 CA180822) and NRG Operations (U10CA180868). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Alabama at Birmingham, Washington University School of Medicine, University of Oklahoma Health Sciences Center, Carolinas Medical Center/Levine Cancer Institute, UC San Diego Moores Cancer Center, UCSF-Mount Zion, Johns Hopkins University/Sidney Kimmel Cancer Center, Stony Brook University Medical Center, Saint Joseph's Hospital and Medical Center, University of Michigan Health System-Cancer Center, Sinai Hospital of Baltimore, University of Texas Medical Branch and the University of Virginia. Funding Information: Dr. Don Dizon received monies for consultancy from Clovis, Regeneron and AstraZeneca. His institution received grants/pending grants from Bristol Myers Squibb , Kazia , Tesaro and Lilly . Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = sep,

doi = "10.1016/j.ygyno.2020.06.493",

language = "English (US)",

volume = "158",

pages = "562--569",

journal = "Gynecologic oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

number = "3",

}

Huh, WK, Brady, WE, Fracasso, PM, Dizon, DS, Powell, MA, Monk, BJ, Leath, CA, Landrum, LM, Tanner, EJ, Crane, EK, Ueda, S, McHale, MT & Aghajanian, C 2020, 'Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study', Gynecologic oncology, vol. 158, no. 3, pp. 562-569. https://doi.org/10.1016/j.ygyno.2020.06.493

TY - JOUR

T1 - Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma

T2 - An NRG oncology/gynecologic oncology group study

AU - Huh, Warner K.

AU - Brady, William E.

AU - Fracasso, Paula M.

AU - Dizon, Don S.

AU - Powell, Matthew A.

AU - Monk, Bradley J.

AU - Leath, Charles A.

AU - Landrum, Lisa M.

AU - Tanner, Edward J.

AU - Crane, Erin K.

AU - Ueda, Stefanie

AU - McHale, Michael T.

AU - Aghajanian, Carol

N1 - Funding Information: Dr. William Brady's institution received grant funding from the NCI . He received support for travel to meetings for the study or other purposes from Advaxis. He also received money paid to him from Sarah Cannon Development Innovations. Funding Information: Dr. Carol Aghajanian reports personal fees from Tesaro, personal fees from Immunogen, grants and personal fees from Clovis , personal fees from Mateon Therapeutics, grants from Genentech , grants from AbbVie , grants from AstraZeneca , personal fees from Eisai/Merck, outside the submitted work. Funding Information: Dr. Charles Leath's institute received grant money from the NIH . His institution also received grants/grants pending for contracted research for recurrent cervical cancer from Agenus . Funding Information: This study was supported by National Institute of Health grants to NRG Oncology ( 1U10 CA180822 ) and NRG Operations ( U10CA180868 ). Funding Information: Dr. William Brady's institution received grant funding from the NCI. He received support for travel to meetings for the study or other purposes from Advaxis. He also received money paid to him from Sarah Cannon Development Innovations.Dr. Don Dizon received monies for consultancy from Clovis, Regeneron and AstraZeneca. His institution received grants/pending grants from Bristol Myers Squibb, Kazia, Tesaro and Lilly.Dr. Bradley Monk's institution received Grant money from Advasix and Genentech. He received money from Advaxis, Genentech and Genmab for consulting free or honorarium. He received fee for participation in review activities such as data monitoring boards, statistical analysis, end point committees and the like from Advaxis. Dr. Monk also received money paid to him for consultancy from Advaxis, Genentech and Genmab. His institution has grants/grants pending from Advaxis, Genentech and Genmab. He received payment for lectures, including service on speakers bureaus from Genentech as well as payment for development of educational presentations. He also has received money from Advaxis for stock/stock options.Dr. Charles Leath's institute received grant money from the NIH. His institution also received grants/grants pending for contracted research for recurrent cervical cancer from Agenus.Dr. Carol Aghajanian reports personal fees from Tesaro, personal fees from Immunogen, grants and personal fees from Clovis, personal fees from Mateon Therapeutics, grants from Genentech, grants from AbbVie, grants from AstraZeneca, personal fees from Eisai/Merck, outside the submitted work.This study was supported by National Institute of Health grants to NRG Oncology (1U10 CA180822) and NRG Operations (U10CA180868). The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: University of Alabama at Birmingham, Washington University School of Medicine, University of Oklahoma Health Sciences Center, Carolinas Medical Center/Levine Cancer Institute, UC San Diego Moores Cancer Center, UCSF-Mount Zion, Johns Hopkins University/Sidney Kimmel Cancer Center, Stony Brook University Medical Center, Saint Joseph's Hospital and Medical Center, University of Michigan Health System-Cancer Center, Sinai Hospital of Baltimore, University of Texas Medical Branch and the University of Virginia. Funding Information: Dr. Don Dizon received monies for consultancy from Clovis, Regeneron and AstraZeneca. His institution received grants/pending grants from Bristol Myers Squibb , Kazia , Tesaro and Lilly . Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/9

Y1 - 2020/9

N2 - Objective: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). Methods: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). Results: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3–12.1) and median PFS was 2.8 months (95% CI: 2.6–3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. Conclusion: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.

AB - Objective: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). Methods: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). Results: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3–12.1) and median PFS was 2.8 months (95% CI: 2.6–3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. Conclusion: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.

KW - HPV

KW - Immunotherapy

KW - Listeria

KW - Metastatic

KW - Recurrent cervical cancer

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Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study

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UN SDGs

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