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.

Conflict of interest statement

Declaration of Competing Interest Dr. Warner Huh received money for consultancy from Inovio and Antiva. 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. Paula Fracasso reports that she became an employee of Bristol-Myers Squibb Company (BMS) as of 5/1/14, and as such, she has stock with the company. Prior to her employment with BMS, she was a professor of Medicine and Obstetrics and Gynecology at the University of Virginia where she is now affiliated as a Visiting Professor of Medicine and Obstetrics and Gynecology. Her work on this clinical study was done while she was a Professor at the University of Virginia and no aactivities in this work have any relationship to her work at BMS. 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. Matthew Powell received monies for consultancy from Merck, Tesaro, Clovis Oncology, AstraZeneca, Abbvie, Janssen and Eisai. He also received payment for lectures, including service on speakers bureaus from Merck, Tesaro, Clovis Oncology and AstraZeneca. 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. Erin Crane received New Investigator Travel Award from NRG. She received money from Tesaro/GSK for Speaker's Bureau. Dr. Michael McHale received money for advisory board consultancy from Eisai. He also received money for payment for lectures, including speakers bureau, from Tesaro. 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.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1.

GOG/NRG-0265 study schema ADXS-HPV Monotherapy 1×109 CFU x 3 doses* q 28 days (month 1, 2, 3) as a 250 mL infusion over 60 min *Stage 2 amended to allow continuous (>3) dosing of ADXS-HPV. CFU, colony-forming units; GOG, Gynecologic Oncology Group

Figure 2.

GOG-0265 CONSORT diagram Study complete *Maximum of 3 doses allowed on stage 1 protocol ADXS-HPV placed on clinical hold N=10 volunteers still receiving ADXSHPV at time of hold N=4, ≥3 doses N=6,

Figure 3.

Survival of volunteers treated in both stages of the study A. 12-month OS rate overall, and B. PFS overall.

Figure 3.

Survival of volunteers treated in both stages of the study A. 12-month OS rate overall, and B. PFS overall.

Figure 3.

Survival of volunteers treated in both stages of the study A. 12-month OS rate overall, and B. PFS overall.