On May 27, 2022 City of Hope, one of the largest cancer research and treatment organizations in the United States, reported it would present research on promising treatments for bladder and blood cancers, as well as studies on precision medicine and an experimental cancer vaccine, at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) annual conference from June 3 to 7 in Chicago (Press release, City of Hope, MAY 27, 2022, View Source [SID1234615209]).
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More than 40,000 oncology professionals and others will attend the conference, or join virtually, to learn about the latest scientific research on cancer treatment, detection and prevention.
"For the first time in two years, our doctors and scientists will meet in person to present the innovative cancer research that City of Hope is known for and learn from colleagues," said Steven T. Rosen, M.D., City of Hope provost and chief scientific officer and Irell & Manella Cancer Center Director’s Distinguished Chair. "City of Hope’s commitment to expand access to specialty cancer care and remove barriers for underserved patients also aligns closely with ASCO (Free ASCO Whitepaper)’s conference theme this year to advance equitable care through innovation."
City of Hope doctors and scientists will present oral and poster presentations on a wide range of topics:
Cabozantinib shows enhanced response to checkpoint inhibitor in patients with solid tumors
Findings from three groups of the COSMIC-021 study show benefit of cabozantinib plus atezolizumab in certain patients with locally advanced or metastatic urothelial carcinoma.
Cabozantinib is a tyrosine kinase inhibitor that may enhance a patient’s response to immune checkpoint inhibitors, which can help the body’s immune system fight cancer. COSMIC-021 is a multicenter Phase 1b study evaluating cabozantinib plus atezolizumab (an anti‒PD-L1 therapy) in patients with various solid tumors (NCT03170960). The findings from cohorts 3, 4 and 5 will be presented during an oral presentation at ASCO (Free ASCO Whitepaper)’s Annual Meeting on Friday, June 3, at 3:57 p.m. CDT.
The study enrolled patients with locally advanced or metastatic urothelial carcinoma, including cancer of the bladder, renal pelvis, ureter and urethra. Patients in cohorts 3 and 4 had not undergone previous therapy and were either eligible for cisplatin-based chemotherapy, cohort 4, or were not eligible for it, cohort 3. Patients in cohort 5 had been previously treated with an immune-checkpoint inhibitor, but not with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor.
"Cabozantinib plus atezolizumab demonstrated encouraging clinical activity with manageable toxicity in patients with inoperable locally advanced or metastatic urothelial carcinoma," said Sumanta Kumar Pal, M.D., co-director of City of Hope’s Kidney Cancer Program and the study’s primary investigator. "The therapy has promise both as a first-line systemic therapy in patients who haven’t been treated with cisplatin-based chemotherapy and as a second-line therapy in patients who have been treated with an immune-checkpoint inhibitor."
After enrollment in the trial, the patients were followed by computed tomography and magnetic resonance imaging scans performed every six weeks for the first year and every 12 weeks thereafter. The study sought to measure the objective response rate, which is the proportion of patients with a complete or partial response, as assessed by use of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a standard way to measure a tumor’s response to treatment. Thirty patients were enrolled in both cohorts 3 and 4. Thirty-one patients were enrolled in cohort 5.
Cabozantinib plus atezolizumab demonstrated clinical benefit in all groups. The objective response rate was 20%, 30% and 10% in cohorts 3, 4 and 5, respectively. One patient in cohort 3 (3%) and two patients in cohort 4 (7%) achieved a complete response. Median overall survival was approximately 14 months in cohorts 3 and 4 and eight months in cohort 5.
The most common treatment-related side effects were diarrhea, aspartate aminotransferase increase, decreased appetite, alanine aminotransferase increased, fatigue and nausea. Grade 3 or 4 side effects, which can be more severe, were reported by 63%, 43% and 45% of cohorts 3, 4 and 5, respectively.
Early results show efficacy of acalabrutinib in patients with marginal zone lymphoma
Results from a clinical trial of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma will be presented at this year’s ASCO (Free ASCO Whitepaper) meeting in a poster session on Saturday, June 4, at 8 a.m. CDT.
Marginal zone lymphomas are a type of B cell non-Hodgkin lymphoma. Few treatment options are available for patients whose disease reappears after a period of remission, known as a relapse, or in those whose lymphoma does not respond to treatment, known as refractory.
Acalabrutinib is a potent next-generation Bruton tyrosine kinase (BTK) inhibitor. These inhibitors block an enzyme in a signaling pathway involved in the growth and survival of some B cell leukemias and lymphomas. BTK inhibitors have been shown to have durable responses in patients with relapsed or refractory marginal zone lymphoma.
Acalabrutinib monotherapy is being studied in a Phase 2 clinical trial at City of Hope and other comprehensive cancer centers across the country. In the trial, patients received 100 mg of acalabrutinib twice daily until their disease progressed or they experienced negative effects.
"Our early results indicate that acalabrutinib is efficacious and well-tolerated in patients with relapsed or refractory marginal zone lymphoma," said Elizabeth Budde, M.D., Ph.D., City of Hope associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, and the abstract’s lead author. "We now have data from 42 patients who were treated through October 2021, and all of them tolerated the therapy well."
The overall response rate in the 37 patients in whom this outcome measure could be evaluated was 54%. Of those patients, six had a complete response, 14 had partial responses and 17 patients had stable disease.
Most side effects were mild. Sixteen patients experienced side effects of grade 3 or higher, most commonly anemia, shortness of breath, fatigue, and reduced numbers of white blood cells, platelets and neutrophils. Two patients discontinued treatment because of serious side effects.
The study concluded that acalabrutinib is a promising treatment in patients with relapsed or refractory marginal zone lymphoma, which is considered incurable when it recurs.
Racial differences in the mutational landscape of serous endometrial cancer
Racial disparities persist in outcomes of endometrial cancer, the most common form of uterine cancer. To identify genetic differences in tumors that may contribute to worse prognosis, a team at Cancer Treatment Centers of America (CTCA), part of City of Hope, has analyzed comprehensive genomic profiling data from a large series of patients with serous endometrial cancer. The team is led by Julian Schink, M.D., chief medical officer of CTCA.
Tumors have genetic changes unique to an individual patient that can be targeted for therapy as part of a precision medicine approach. The 2022 National Comprehensive Cancer Network (NCCN) Guidelines for uterine neoplasms recommend genetic evaluation of tumors as part of the initial evaluation of a patient. In this study, the team analyzed data from 86 patients, of whom 37% were white, 58% were Black and 5% were Asian.
Schink and his team found genetic alterations in 94% of the patients. TP53 mutations, which are characteristic of serous cancer, were present in 93% of the patients.
However, they noted some racial differences in the genomic alterations identified. Alterations that are predicted to activate the phosphatidylinositol 3-kinase signaling pathway, which regulates cell proliferation and survival, were significantly more common in white women than in Black women (41% vs. 16%). These alterations included mutations in the genes PIK3CA, PIK3R1 and PTEN.
Amplification of CCNE1 was also noted more often in Black women, although this difference was not statistically significant.
"PIK3CA mutations are an important factor in resistance to anti-HER2 therapy, a treatment that targets the HER2 protein. Also, increased CCNE1 amplification has been linked to the racial disparities seen in cancer outcomes," said Schink, the abstract’s lead author. "Thus, identifying these racial differences in genomic alterations may help to explain the disparities we see with endometrial cancer and better inform therapy selection."
Study data on abstract 5600 will be presented in a poster session at the ASCO (Free ASCO Whitepaper) conference on Saturday, June 4, beginning at 1:15 p.m. CDT.
Initial findings for Nous-209 cancer vaccine combined with pembrolizumab
A promising off-the-shelf cancer vaccine called Nous-209 is being studied at City of Hope in patients with dMMR/MSI-H tumors (defective DNA mismatch repair/high microsatellite instability). These tumors have abnormalities that affect a cell’s ability to repair DNA, resulting in an accumulation of errors in a tumor’s genetic sequences.
Initial clinical outcomes in 20 patients enrolled in the Phase 1 study of Nous-209 in combination with the immune checkpoint inhibitor pembrolizumab will be presented in a poster discussion session at the ASCO (Free ASCO Whitepaper) conference on Sunday, June 5, at 11:42 a.m. CDT. Pembrolizumab is an antibody that blocks a protein called programmed death receptor-1 (PD-1). Marwan Fakih, M.D., City of Hope’s Judy & Bernard Briskin Distinguished Director of Clinical Research and professor, Department of Medical Oncology & Therapeutics Research, is the abstract’s lead author.
"The combination of the NOUS-209 cancer vaccine and pembrolizumab continues to be found to be safe and highly immunogenic," Fakih said. "Our promising findings for the early and long-term clinical efficacy of this combination may be attributable to the vaccine contribution."
Patients in the trial had dMMR/MSI-H colorectal, gastric or gastro-esophageal junction tumors that were metastatic or could not be removed with surgery. The drug combination was tested as a second-line therapy in patients whose disease had progressed despite prior treatment and as a first-line therapy in patients who refused or were ineligible for chemotherapy. None of the patients had previously been treated with pembrolizumab.
Investigators assessed tumor responses to the drug combination using the RECIST v1.1 guidelines. To date, 10 patients have shown a durable partial response to treatment, four showed durable stable disease and six showed progressive disease. Four of the six patients who showed disease progression did not receive the full vaccination schedule.
Nous-209 plus pembrolizumab was well tolerated and had a favorable safety profile. The most common treatment-related adverse events were nausea, diarrhea and fatigue, in 35%, 25% and 25% of the patients, respectively.
dMMR/MSI tumors carry tumor-specific frameshift peptides, which are produced as the result of the errors in the tumor’s DNA sequence. The Nous-209 vaccine carries the instructions to target 209 different frameshift peptides that dMMR/MSI tumors have in common. A tumor in any one patient will share 50 frameshift peptides on average with the Nous-209 vaccine. Thus, a patient’s own anti-tumor immune response can be activated after vaccination with Nous-209.
Future analyses are planned to further test the efficacy of Nous-209 and explore endpoints, such as the quality of the patient’s T cell responses to the vaccine.
City of Hope oncology chair receives prestigious ASCO (Free ASCO Whitepaper) award and experts serve on ASCO (Free ASCO Whitepaper) panels discussing health equity, cancer and aging, CAR T cell therapy and supportive care
Ravi Salgia, M.D., Ph.D, City of Hope’s Arthur & Rosalie Kaplan Chair in Medical Oncology, will receive the Excellence in Teaching Award on Saturday, June 4 at 1:34 p.m. CDT.
Edward Kim, M.D., M.B.A., physician-in-chief, City of Hope Orange County, and vice physician-in-chief, City of Hope National Medical Center, will speak on an education session titled "Expanding Clinical Trial Eligibility to Improve Their Generalizability and Advance Equity" on Sunday, June 5, at 9:45 a.m. CDT.
William Dale, M.D, Ph.D., City of Hope’s Arthur M. Coppola Family Chair in Supportive Care Medicine, will speak on a geriatric oncology education session to discuss early integration of palliative medicine for locally advanced and metastatic genitourinary malignancies on Sunday, June 5, at 4:48 p.m. CDT.
Tanya Dorff, M.D., City of Hope’s section chief, Genitourinary Disease Program, will speak on a case-based panel titled "CAR T for Prostate Cancer: Current Strategies to Improve Efficacy" on Monday, June 6, at 9:00 a.m. CDT.
Richard T. Lee, M.D., medical director of City of Hope’s Integrative Medicine Program, will serve on a panel titled "Highlights of the Care Delivery and Regulatory Policy Track" on Tuesday, June 7, at 9:12 a.m. CDT.