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

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

doi:10.1016/j.ygyno.2020.06.493

Cited by 47 publications

(32 citation statements)

References 25 publications

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“…In terms of safety, the difference between these two arms was more pronounced with more AEs observed in the Lm-LLO-E7+cisplatin group (429) than the Lm-LLO-E7 alone group (275) but most of these AEs were mild to moderate in severity (80.4%). These results informed the second Phase II trial for cervical cancer funded by the NCI, wherein, there was only a single arm receiving three doses of Lm-LLO-E7 only in the first stage, with some patients receiving an additional three doses in a second stage (42). Treatment-related AE types and frequencies were similar to previous trials with nearly all patients experiencing at least one and 38% experiencing a grade 3 AE.…”

Section: Hpv-associated Cancerssupporting

confidence: 74%

“…The recent results reported from several clinical trials demonstrate the promising future of Lm-based tumor immunotherapies but also reveal challenges that educate the future development of the platform (41,42,60). Numerous improvements to the platform have already been reported in preclinical studies that would not be evident in the clinical results as they are mostly utilizing first-generation Lm-based constructs (29,30,78).…”

Section: Discussionmentioning

confidence: 99%

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Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

2021

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The promise of tumor immunotherapy to significantly improve survival in patients who are refractory to long-standing therapies, such as chemotherapy and radiation, is now being realized. While immune checkpoint inhibitors that target PD-1 and CTLA-4 are leading the charge in clinical efficacy, there are a number of other promising tumor immunotherapies in advanced development such as Listeria-based vaccines. Due to its unique life cycle and ability to induce robust CTL responses, attenuated strains of Listeria monocytogenes (Lm) have been utilized as vaccine vectors targeting both infectious disease and cancer. In fact, preclinical studies in a multitude of cancer types have found Listeria-based vaccines to be highly effective at activating anti-tumor immunity and eradicating tumors. Several clinical trials have now recently reported their results, demonstrating promising efficacy against some cancers, and unique challenges. Development of the Lm-based immunotherapies continues with discovery of improved methods of attenuation, novel uses, and more effective combinatorial regimens. In this review, we provide a brief background of Listeria monocytogenes as a vaccine vector, discuss recent clinical experience with Listeria-based immunotherapies, and detail the advancements in development of improved Listeria-based vaccine platforms and in their utilization.

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Section: Hpv-associated Cancerssupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

2021

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“…Since then, the standard of care for recurrent cervical cancer has moved to include doublet platinum-based chemotherapy and bevacizumab when tolerated. A follow-up study of ADXS11-001 in 50 patients with advanced platinum-refractory cervical cancer demonstrated a 12-month OS of 38%, which compared favorably with the historical 12-month survival rate of 21% (92). The study did not include correlative analyses; thus, it is unclear whether the clinical benefit observed on the study correlated with an HPV-specific T-cell response.…”

Section: Therapeutic Vaccination Strategiesmentioning

confidence: 98%

Tumor Immunity and Immunotherapy for HPV-Related Cancers

et al. 2021

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Human papillomavirus (HPV) infection drives tumorigenesis in the majority of cervical, oropharyngeal, anal, and vulvar cancers. Genetic and epidemiologic evidence has highlighted the role of immunosuppression in the oncogenesis of HPV-related malignancies. Here we review how HPV modulates the immune microenvironment and subsequent therapeutic implications. We describe the landscape of immunotherapies for these cancers with a focus on findings from early-phase studies exploring antigen-specific treatments, and discuss future directions. Although responses across these studies have been modest to date, a deeper understanding of HPV-related tumor biology and immunology may prove instrumental for the development of more efficacious immunotherapeutic approaches.Significance: HPV modulates the microenvironment to create a protumorigenic state of immune suppression and evasion. Our understanding of these mechanisms has led to the development of immunomodulatory treatments that have shown early clinical promise in patients with HPV-related malignancies. This review summarizes our current understanding of the interactions of HPV and its microenvironment and provides insight into the progress and challenges of developing immunotherapies for HPV-related malignancies.

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“…17 A follow-up study of ADXS11-001 in 50 patients with advanced cervical cancer demonstrated an overall response rate of only 6% but with 12-month overall survival of 38%, which compared favorably to the historical 12month survival rate of 21%. 18 A study of an HPV16 synthetic long peptide vaccine in 13 patients with advanced cervical cancer demonstrated an overall response rate of 0%, despite the evidence of vaccine-induced T-cell response in most patients. 19 Overall, although therapeutic vaccination against HPV E6 and E7 demonstrates compelling evidence for induction of HPV-specific immune responses and regression of…”

Section: Hpv-directed Vaccinesmentioning

confidence: 99%

Expanding Our Impact in Cervical Cancer Treatment: Novel Immunotherapies, Radiation Innovations, and Consideration of Rare Histologies

Randall

Walker

Jia

et al. 2021

American Society of Clinical Oncology Educational Book

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Cervical cancer is a socially and scientifically distinguishable disease. Its pathogenesis, sexual transmission of high-risk HPV to a metaplastic portion of the uterine cervix, makes cervical cancer preventable by safe and effective HPV vaccines commercially available since 2006. Despite this, cervical cancer remains the deadliest gynecologic cancer in the world. Regrettably, global incidence and mortality rates disproportionately affect populations where women are marginalized, where HIV infection is endemic, and where access to preventive vaccination and screening for preinvasive disease are limited. In the United States, cervical cancer incidence has gradually declined over the last 25 years, but mortality rates remain both constant and disparately higher among communities of color because of the adverse roles that racism and poverty play in outcome. Until these conditions improve and widespread prevention is possible, treatment innovations are warranted. The last standard-of-care treatment changes occurred in 1999 for locally advanced disease and in 2014 for metastatic and recurrent disease. The viral and immunologic nature of HPV-induced cervical cancer creates opportunities for both radiation and immunotherapy to improve outcomes. With the advent of T cell–directed therapy, immune checkpoint inhibition, and techniques to increase the therapeutic window of radiation treatment, an overdue wave of innovation is currently emerging in cervical cancer treatment. The purpose of this review is to describe the contemporary developmental therapeutic landscape for cervical cancer that applies to most tumors and to discuss notable rare histologic subtypes that will not be adequately addressed with these treatment innovations.

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

Cited by 47 publications

References 25 publications

Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

Tumor Immunity and Immunotherapy for HPV-Related Cancers

Expanding Our Impact in Cervical Cancer Treatment: Novel Immunotherapies, Radiation Innovations, and Consideration of Rare Histologies

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