ACCCF Research Update
November 2020
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The ACCRF website (www.accrf.org) recently got a makeover. The goals were to:
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Help patients find key information more easily, depending upon the stage of disease or the treatments being considered.
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Help researchers find key information more easily, whether research tools, molecular targets or grant awards.
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Facilitate community building among patients and researchers.
Let us know what you think! Please email us at info@accrf.org with comments, questions and suggestions. The website is a living resource that we will update with fresh information and new sections. Your guidance will make it better!
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Despite the enormous and tragic impact of the COVID-19 pandemic, ACCRF’s research network has continued to press forward in seeking better treatments for patients. This year has seen an expansion in the number of ACC clinical trials to record levels. ACC patients currently have the widest availability ever of options based on study locations and types of drugs. Since our spring update, there have been some important developments, including the opening or expansion of the following studies:
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Lenvatinib + Pembrolizumab (VEGFR + PD-1 inhibitors) – Following up on a phase II study of Lenvatinib in which 5 of 32 ACC patients had a partial response (significant tumor shrinkage), this study combines Lenvatinib with a PD-1 immunotherapy drug. It is open in New York, NY, USA.
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GSK3326595 (PRMT5 inhibitor) – In a phase I clinical trial, 3 of 14 ACC patients had a partial response (significant tumor shrinkage). An expansion cohort for ACC patients recently opened at multiple sites in Canada, France, Netherlands and USA. Only ACC patients without previous systemic therapy (drugs) are eligible.
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PRT-543 (PRMT5 inhibitor) – With the same molecular target as GSK3326595, this study is now open for ACC patients in Houston, TX, USA.
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CB-103 (NOTCH inhibitor) – Already open in Spain and Switzerland, this study recently opened in the USA as well (Houston, TX, and Santa Monica, CA). Only ACC patients with NOTCH-activated tumors are eligible.
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AL101 (NOTCH inhibitor )– This study recently expanded with a higher dose in locations throughout Europe and North America. Only ACC patients with NOTCH-activated tumors are eligible.
Meanwhile some studies completed their enrollment of ACC patients:
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Rivoceranib (Apatinib) – Following an increase in size from 55 to 72 patients, this clinical trial has completed enrollment in the USA and Korea. We hope for preliminary reports in the spring.
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ATRA – Following an increase in patients and dosing levels, this clinical trial completed enrollment in Boston, MA, USA. We anticipate preliminary reports in the spring.
For patients considering systemic therapy, we list clinical trials that are currently enrolling patients on our Open Studies webpage. ACC patients and their physicians may review the results of past clinical trials on our Completed Studies webpage. We summarize the history of ACC-focused clinical trials, highlighting drugs that appear to show some effectiveness (although none have been approved by regulatory authorities for ACC).
Systemic therapy and clinical trials typically are considered for only ACC patients with advanced metastatic disease. In all cases, patients should consult with a knowledgeable physician when considering clinical trials or any treatment.
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The COVID-19 pandemic forced the closure of most research laboratories for several months during 2020. Many have partially reopened with researchers often constrained in accessing their labs or shipping specimens and models. Despite these challenges, ACCRF grantees continue to generate and report new findings that will lay the foundation for future clinical trials and better treatments for ACC patients. Here we review some recent publications in scientific journals:
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Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets – Dr. Adel El-Naggar, Dr. Renata Ferrarotto and their colleagues at MD Anderson (Houston, TX, USA) analyzed genomic data sets to group ACC tumors into two categories with implications for prognoses and treatments. One group, representing just over one-third of ACC tumors, was particularly enriched with MYC and NOTCH pathway proteins, exhibiting a worse prognosis. The other group, representing nearly two-thirds of ACC tumors, were particularly enriched with TP63, AXL, MET and EGFR proteins, and had a better prognosis.
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A Randomized Phase 2 Study of Pembrolizumab With or Without Radiation in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma – Dr, Jon Schoenfeld and colleagues at the Dana-Farber Cancer Institute and the Massachusetts General Hospital (Boston, MA, USA) recently published the results of their clinical trial of a PD-1 inhibitor (Pembrolizumab/Keytruda) alone or in combination with radiation. Half of patients delayed their disease progress for 6 months or longer, a moderately encouraging outcome. However, the addition of radiation to Pembrolizumab did not increase the percentage of patients that achieved stable disease. In patients who received radiation to some of their tumors, there were no objective responses (major tumor shrinkage) in tumors that were not irradiated, indicating no apparent “abscopal effect”.
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Time to Debunk an Urban Myth? The "Abscopal Effect" With Radiation and Anti-PD-1 – Dr. Tanguy Swiwert and Dr. Ana Kiess at Johns Hopkins University (Baltimore, MD, USA) wrote a commentary on the abscopal effect in head and neck cancer cases. Similar to Dr. Schoenfeld's findings in ACC, there were no consistent abscopal responses in squamous cell carcinoma tumors in a study carried out by Dr. Alan Ho and colleagues at Memorial Sloan Kettering (New York, NY, USA). ACCRF is supporting an additional study by Dr. Stephen Doggett at Mission Hospital (Tustin, CA, USA) that is evaluating whether the abscopal effect may be elicited with brachytherapy, a different method of delivering radiation to tumors.
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Patients can have a direct impact on finding new ways to fight ACC. By donating tumor specimens from upcoming surgeries, patients permit researchers to create new cell lines (human tumors growing in plastic dishes) that help identify disease vulnerabilities and new targets for therapies. At the Broad Institute of MIT and Harvard, the Rare Cancer Dependency Map Initiative is creating ACC cell lines from living tissue and then analyzing them with genomic (CRISPR) and drug screens. The effort is described in this video.
If you have an upcoming surgery scheduled in the United States, you can help this initiative by donating excess tissue from your procedure. It is free and won't interfere with your treatment. Go to Pattern.org to learn more about tumor donations.
ACCRF is proud to support the work of Pattern.org and the Broad Institute for the benefit of ACC patients.
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Brave Like Gabe Raises $80,000 to Support ACCRF Research
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Even in a pandemic, thousands of people were inspired by the Brave Like Gabe Foundation to "Run on Hope". During the weekend of September 6th, thousands of supporters laced up their running shoes and headed outside to raise funds for better treatments for ACC. The Brave Like Gabe Foundation continued its fabulous support of ACCRF by passing along $80,000 for research! #runningonhope
ACCRF Board Member Douglas Meyer (pictured on left) spent the weekend #runningonhope in Saratoga Springs, NY
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