Newsbriefs

Petten HFR Restarts Production

NRG (Petten and Arnhem, The Netherlands) announced on March 17 that its High Flux Reactor (HFR) in Petten had been restarted that morning and reached a power output of 45 MW. “Within 2 wk, the first medical isotopes for nuclear medicine will be delivered to hospitals,” said Vinod Ramnandanlal, commercial director for NRG and its project partner PALLAS. “We are pleased that NRG can once again meet the global demand for medical isotopes.”

The HFR did not start a scheduled production run on 20 January because of a leak in a test facility water system outside of the reactor core. NRG initiated inspections and preparations to restore the system. This required modifications to the facility and submission of an application for regulatory review and approval. This permit was granted on March 9. Directors and staff at reactors in Europe and the United States changed production schedules and methods during the Petten outage to meet radioisotope supply demands.

“This is extremely good news. Medical isotopes are of enormous importance for many patients,” said Andor Glaudemans, MD, PhD, president of the Dutch Association for Nuclear Medicine.

The HFR was commissioned in 1961 to develop nuclear technology for energy generation. Beginning in the 1980s, the reactor was increasingly used for production of medical isotopes, particularly for diagnostic applications. Today >30,000 patients/d are treated with medical isotopes from the HFR.

NRG

FDA Guidances Target Cancer Clinical Trials

On March 1, the U.S. Food and Drug Administration (FDA) issued 3 final guidances for industry related to cancer clinical trials. In a press release, the FDA noted that these guidances “parallel the goals of President Biden’s recently announced effort to renew and build upon his 2016 Cancer Moonshot initiative to facilitate continued advancement in cancer prevention, detection, research, and patient care.” The goals for this renewed initiative are: to reduce death rates from cancer by at least 50% over the next 25 years, to improve the experience of people and their families living with and surviving cancer, and “to end cancer as we know it today.”

“With today’s actions the FDA is recommending important principles that involve addressing inequities, targeting the right treatments to the right patients, speeding progress against the most deadly and rare cancers, and learning from the experience of all patients,” said Richard Pazdur, MD, director for the FDA’s Oncology Center for Excellence. “All of these are tenets of Cancer Moonshot’s mission.”

The first new finalized guidance, “Inclusion of Older Adults in Cancer Clinical Trials,” provides recommendations to sponsors and institutional review boards for including older patients (≥65 y) in clinical trials of drugs for cancer treatment. Enrollment of older adults in early-phase cancer clinical trials is recommended, as appropriate, to better inform later-phase studies. Also included are recommendations for trial design, recruitment strategies, information collection, and developing and reporting on more precisely defined older age groups to encourage trial enrollment of this historically excluded population. This guidance is available at: https://public-inspection.federalregister.gov/2022-04399.pdf.

The second new guidance for industry is “Expansion Cohorts: Use in First-in-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics.” Advice is provided on designing and conducting trials with multiple expansion cohorts that allow for concurrent accrual of patients into different cohorts to assess safety, pharmacokinetics, and antitumor activity of first-in-human cancer drugs. Pharmaceutical companies and researchers can use trials with expansion cohort designs to assess different aspects of a drug in a single clinical trial to expedite efficient clinical development of the drug. This guidance is available at: https://public-inspection.federalregister.gov/2022-04397.pdf.

The new guidance on “Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics” addresses master protocol design, including information on what sponsors should submit to the FDA as part of these trial approaches. It also directs sponsors on interactions with the FDA to facilitate efficient review and mitigate risks to patients. These clinical trials can expedite clinical development of a drug by allowing more than 1 investigational drug or biologic, more than 1 disease type, or more than 1 patient population to be evaluated under a single clinical trial structure. This guidance is available at: https://public-inspection.federalregister.gov/2022-04398.pdf.

All FDA Oncology Center of Excellence documents are available through the portal at: https://www.fda.gov/about-fda/oncology-center-excellence/oncology-center-excellence-guidance-documents.

U.S. Food and Drug Administration

NCI and Molecular Characterization of Childhood Cancers

The National Cancer Institute (NCI) announced on March 21 the launch of the Molecular Characterization Initiative for pediatric tumors. The program, hosted by NCI’s Childhood Cancer Data Initiative, offers tumor molecular characterization (biomarker testing) to children, adolescents, and young adults with newly diagnosed central nervous system tumors who are being treated at hospitals affiliated with the Children’s Oncology Group (COG). This NCI-supported clinical trials group includes more than 200 hospitals and institutions treating children diagnosed with cancer in the United States.

Participants with central nervous system cancers will be eligible to receive molecular characterization of their tumors free of charge through this voluntary program. DNA and RNA from tumor and blood samples will be analyzed, and, later in 2022, the program will be expanded to include soft tissue sarcomas and other rare tumors.

“The ultimate dream has really been for every child with cancer to have a state-of-the-art diagnosis and the safest and most effective therapy,” said Brigitte C. Widemann, MD, special advisor to the NCI director for childhood cancer. “The Molecular Characterization Initiative is a transformative collaboration that will entail participation of the entire community.”

Comprehensive tumor molecular characterization has previously been available to children enrolling in some clinical trials or being treated at larger institutions with internal resources that offer such state-of-the-art diagnostics. Data on tumor biomarkers have been stored exclusively at the hospital or institution at which a child was treated, with limited data sharing among institutions. The new program will make tumor molecular characterization broadly available, with data collected in a central location accessible to researchers.

“We can help make molecular characterization available throughout the country so that it will be a standard of care that every child can get,” said Maryam Fouladi, MD, leader of the COG central nervous system tumor disease committee. “An accurate molecular diagnosis can inform optimal treatment for every child.”

In addition to providing detailed information to use in making an accurate diagnosis, the data can also be used to determine whether a child is eligible for a clinical trial. Enrollment in the Molecular Characterization Initiative is initially offered through participation in Project Every Child (http://www.projecteverychild.org/), a childhood cancer registry maintained by COG. Initial participants will include newly diagnosed children, adolescents, and young adults ≤25 y old at the time of diagnoses. Young adults >25 y old who are being screened for eligibility into a COG clinical trial may also be included. Additional information on the initiative is available at: https://www.cancer.gov/research/areas/childhood/childhood-cancer-data-initiative/molecular-characterization.

National Cancer Institute

NIH All of Us Research Program Releases 100,000 Whole-Genome Sequences

The National Institutes of Health (NIH) announced on March 17 the release of nearly 100,000 diverse whole-genome sequences through its All of Us Research Program. About 50% of the data is from individuals who identify with racial or ethnic groups that have historically been underrepresented in research. These data will enable researchers to address new questions about health, disease, and disparities.

“Until now, over 90% of participants from large genomics studies have been of European descent. The lack of diversity in research has hindered scientific discovery,” said Josh Denny, MD, chief executive officer of the All of Us Research Program. “All of Us participants are leading the way toward more equitable representation in medical research through their involvement. And this is just the beginning. Over time, as we expand our data and add new tools, this dataset will become an indispensable resource for health research.”

The genomic data are available via a cloud-based workbench platform (https://www.researchallofus.org/) and also include genotyping arrays from 165,000 participants. Whole-genome sequencing provides information about almost all of an individual’s genetic makeup, whereas genotyping arrays, the more commonly used genetic testing approach, capture a specific subset of the genome.

In addition to the genomic data, the All of Us workbench contains information from many of the participants’ electronic health records, Fitbit devices, and survey responses. The platform also links to data from the Census Bureau’s American Community Survey to provide more details about the communities in which participants live. This combination of data will allow researchers to better understand how genes can cause or influence diseases in the context of other health determinants. The ultimate goal is to enable more precise approaches to health care for all populations. To protect participants’ privacy, the program has removed all direct identifiers from the data and upholds strict requirements for researchers seeking access.

In a press release, NIH noted that these data are made available for research through the contributions of All of Us participants, who have the opportunity to receive personal DNA results at no cost. The program has offered genetic ancestry and trait results to more than 100,000 participants so far, with plans underway to begin to share health-related DNA results on hereditary disease risk and medication–gene interactions later this year. All of Us works with a consortium of partners across the United States to engage participants and collect data and samples. The Researcher Workbench is managed by Vanderbilt University Medical Center, in collaboration with the Broad Institute of MIT and Harvard and Verily. The program’s genome centers generate the genomic data and process about 5,000 participant samples each week. These centers include Baylor College of Medicine, Johns Hopkins University, the Broad Institute, the Northwest Genomics Center at the University of Washington, and partners. Color, a health technology company, works with the program to return personalized results to participants on genetic ancestry and traits and the forthcoming health-related genetic results.

National Institutes of Health