Uterine Cervix Adenocarcinoma

BRONX, N.Y., Sept. 7, 2023 /PRNewswire/ -- In findings with potentially important implications for cervical cancer screening, scientists at the National Cancer Institute (NCI)-designated Montefiore Einstein Cancer Center (MECC) have developed a test for detecting a type of cervical cancer that Pap tests often miss. The findings published online today in the Journal of the National Cancer Institute (JNCI). "Our novel test appears sensitive for detecting cervical adenocarcinoma [ADC]—which now accounts for up to 25% of cervical cancer cases—as well as its precursor lesions, adenocarcinoma in situ [AIS], that often develop into ADCs," said Howard Strickler, M.D., M.P.H., co-senior and corresponding author of the JNCI paper and a member of MECC. "Because ADCs are often missed by current screening methods, they have higher mortality rates than the more common cervical squamous cell cancer," Dr. Strickler added. "Our goal is to catch the disease early, before it develops into cancer." Dr. Strickler is also professor and head of the division of epidemiology and the Harold and Muriel Block Chair in Epidemiology and Population Health at Albert Einstein College of Medicine. A Novel Approach to Testing The widespread use of the Pap test, in which a pathologist examines tissue samples for abnormal cells, has significantly reduced the incidence of cervical squamous cell cancer over the past six decades. However, the incidence of ADC has not decreased, probably because the Pap test is less effective at detecting it. In recent years, testing for human papillomaviruses (HPVs)—which cause virtually all cases of cervical cancer—joined the Pap test as a standard screening tool for cervical cancer. Although there are more than 100 types of HPV, three types—HPV 16, 18, and 45—account for more than 70% of all cervical cancer cases and more than 90% of ADC cases. The current HPV tests cover all three types and can alert infected women that they face a high risk for developing cervical cancer. While vaccines for preventing cervical cancer—including Gardasil-9, which protects against nine HPV types—are safe and effective, several generations of women are above the age for receiving the vaccine. Therefore, screening and treatment for prevention of cervical cancer will remain critical for decades to come. The MECC-developed HPV test assessed HPV 16, 18, and 45 in a novel way: by specifically looking at methylation levels. "The advent of next-generation genetic testing has opened up opportunities for us to more accurately detect oncogenic HPV strains and patterns in the genomes that correspond with the development of AIS and ADC," said Robert D. Burk, M.D., professor of pediatrics, of microbiology & immunology, of epidemiology and population health, and of obstetrics & gynecology and women's health at Einstein and MECC member, who co-led the study. Methylation—the addition of methyl (CH3) groups to a region of DNA—is a routine occurrence in DNA, both viral and human, and plays a critical role in altering gene expression. The JNCI study, a collaborative project with the NCI, part of the National Institutes of Health, investigated methylation levels in cervical tissue samples from 1,400 women who had undergone cervical cancer screening at Kaiser Permanente Northern California before 2014 and whose cervical cancer status was known. In assessing the HPVs in the cytological samples, the researchers tallied up the methylation percentages for each of 35 different viral-genome sites, with each sample receiving a final "methylation score" equal to the average methylation percentage across all 35 sites. Those women with methylation scores in the upper 25% had very high odds for having developed either ADC or AIS. "Our findings, if confirmed by clinical trials, suggest that women with a high methylation score may benefit from colposcopy and specialized tissue evaluation, beyond just a Pap test, which could lead to early diagnosis and treatment for ADC or the removal of AIS lesions before they develop into ADC," said Dr. Burk. Improving Equity in Cervical Cancer Screening "Given that our test uses equipment that could be simplified, it has the potential to expand testing in lower-resourced countries," said Dr. Strickler, who has long studied HPV in women living with HIV, who are more likely to acquire an HPV infection. Cervical cancer remains the fourth most common type of cancer in women, with the burden significantly higher in lower- and middle-income countries, including those in Sub-Saharan Africa, where HIV-HPV coinfections are common. There are also significant disparities within the United States. In New York City, rates of cervical cancer in the Bronx, which is home to the poorest urban congressional district in the country, are 50% higher than in Manhattan. More frequent and effective screening could help address this health disparity. "Ideally, the new HPV methylation test would only need to be done once every three to five years," said Dr. Strickler. "We are hopeful that this test will be able to increase cervical cancer screening equity in the U.S. as well." The paper is titled "A Novel HPV/Host DNA Methylation-Score and Detection of Cervical Adenocarcinoma." In addition to Drs. Strickler and Burk, other Einstein authors on the study were Ana Gradissimo, Ph.D., Xiaonan Xue, Ph.D., and Philip E. Castle, Ph.D, M.P.H. (also affiliated with the NCI). Other contributors were Megan A. Clarke, Ph.D., M.H.S., Mark Schiffman, M.D., M.P.H., and Nicolas Wentzensen, M.D., Ph.D., M.PH., all at NCI, and Tina R. Raine-Bennett, M.D., M.P.H. at Kaiser Permanente. About Montefiore Einstein Cancer Center Montefiore Einstein Cancer Center (MECC) is a national leader in cancer research and care located in the ethnically diverse and economically disadvantaged borough of the Bronx, N.Y. MECC combines the exceptional science of Albert Einstein College of Medicine with the multidisciplinary and team-based approach to cancer care of Montefiore Health System. Founded in 1971 and a National Cancer Institute (NCI)-designated Cancer Center since 1972, MECC is redefining excellence in cancer research, clinical care, education and training, and community outreach and engagement. Its mission is to reduce the burden of cancer for all, especially people from historically marginalized communities. SOURCE Montefiore Einstein Cancer Center

Objective response rate of 20% and median duration of response not reached with 14.6 month median follow-up in PD-L1+ tumors Responses seen across all histology subgroups including populations of patients unresponsive to other therapies LEXINGTON, Mass., Aug. 26, 2021 (GLOBE NEWSWIRE) -- Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapies, adjuvants, and vaccines designed to activate immune response to cancers and infections, today announced that results from a global Phase 2 clinical study of balstilimab monotherapy in recurrent/metastatic cervical cancer were published online in the international peer reviewed journal Gynecologic Oncology ( ). “Publication of these data marks another significant achievement toward our objective to provide effective therapeutic options to those battling cancer,” said Steven O’Day, MD, Chief Medical Officer of Agenus. “These data are drawn from the largest Phase 2 study to date evaluating PD-1 inhibition in advanced cervical cancer patients who have progressed on or after first-line chemotherapy; the results indicate balstilimab’s potential as an effective new therapy.” In the 140 evaluable patients, the objective response rate (ORR) in patients with PD-L1 positive tumors was 20.0% and included 3 patients (3/85, 3.5%) with a complete response and 14 patients (14/85, 16.5%) with a partial response. The median duration of response (DoR) was not reached after a 14.6-month median follow-up. Responses were also observed in the PD-L1 negative population with an ORR of 7.9%. The confirmed ORR for both PD-L1 positive and negative tumors was 15.0% and included 5 patients (3.6%) with a complete response and 16 patients (11.4%) with a partial response. The median DoR was 15.4 months and the disease control rate was ~50%. Notably, responses were observed across histologies, with responses in the squamous cell histology (ORR 17.6%) and in the more difficult to treat adenocarcinoma histology (ORR 12.5%). The safety pro manageable and consistent with that of currently approved anti-PD-1 antibodies; it also compared favorably to the safety profiles of chemotherapies used in this population. Data from this trial continue to mature. As discussed in the publication, these data suggest that balstilimab may be a differentiated anti-PD-1 antibody as compared to currently approved PD-1 inhibitors. In the KEYNOTE-158 trial of pembrolizumab, an anti-PD-1 antibody, in the same setting, an ORR of 14.6% was observed in the PD-L1 positive population and no responses were observed in the PD-L1 negative population. In addition, the noted 12.5% response rate of balstilimab in patients with cervical adenocarcinoma is significant as this subpopulation typically does not respond to immunotherapy and represents a growing proportion of advanced cervical cancer cases. Balstilimab thus provides the potential for therapeutic benefit to patient populations that do not typically respond to currently-available immunotherapy, both alone and in combination with other therapies, such as Agenus’ anti-CTLA-4 antibodies zalifrelimab and AGEN1181. Final results from a Phase 2 trial of balstilimab in combination with zalifrelimab in advanced cervical cancer will be presented in a Mini Oral Session at the European Society for Medical Oncology (ESMO) Congress 2021 on September 19 from 11:35 – 11:40am ET by David O’Malley, MD. “The efficacy and safety of balstilimab provides additional evidence of the importance of immune checkpoint blockade in the treatment of recurrent, advanced cervical cancer patients,” said David O’Malley, MD, Professor, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine; Director, Division of Gynecologic Oncology, OSUCCC – James; and lead author on the publication. “Furthermore, responses to balstilimab were seen in patients who were PD-L1 positive, PD-L1-negative, bevacizumab pre-treated, and squamous cell and adenocarcinoma histologies. Balstilimab clearly provides clinical benefit in a broad range of cervical cancer patients.” Study Design (NCT03104699) This was an open-label, single-arm, global Phase 2 clinical trial conducted at 60 sites throughout the United States, Europe, South America, and Australia. Patients were enrolled from November 20, 2017, to April 16, 2020, and received intravenous balstilimab at a dose of 3 mg/kg once every two weeks, given as a 60-minute infusion. Treatment was permitted for up to 24 months, or until disease progression, intolerable toxicity, or investigator/patient decision. About Balstilimab Monotherapy Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. PD-1 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market. Agenus announced it had submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) on April 19, 2021, for use in patients with recurrent or metastatic cervical cancer, and the application is under priority review with a target action date of December 16, 2021. About Agenus Agenus is a clinical-stage immuno-oncology company focused on the discovery and development of therapies that engage the body's immune system to fight cancer. The Company's vision is to expand the patient populations benefiting from cancer immunotherapy by pursuing combination approaches that leverage a broad repertoire of antibody therapeutics, adoptive cell therapies (through its MiNK Therapeutics subsidiary), adjuvants, and proprietary cancer vaccine platforms. The Company is equipped with a suite of antibody discovery platforms and a state-of-the-art GMP manufacturing facility with the capacity to support clinical programs. Agenus is headquartered in Lexington, MA. For more information, please visit and our Twitter handle @agenus_bio. Information that may be important to investors will be routinely posted on our website and Twitter. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding potential therapeutic benefit and future clinical development plans for balstilimab, zalifrelimab, and AGEN1181 alone and in combination with other agents. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Contact Agenus Investor Relations Jan Medina, CFA Agenus 781-674-4490 Jan.Medina@agenusbio.com Agenus Media Relations Kimberly Ha KKH Advisors 917-291-5744 kimberly.ha@kkhadvisors.com