FDA finalizes three guidances on cancer trials in line with Biden’s ‘Moonshot’

Regulatory NewsRegulatory News | 01 March 2022 |  By 

The US Food and Drug Administration (FDA) announced they have released final guidances for industry on including older adults in cancer clinical trials, conducting first-in-human (FIH) cancer trials with expansion cohorts, and the development of master protocol designs for efficient review of oncology drugs and biologics.
In a press release, the agency said issuing the three final guidances aligns with President Biden’s Cancer Moonshot initiative, originally launched in 2016 by Biden as Vice President. In February 2022, the effort was reignited with new objectives. Under the renewed Cancer Moonshot, the Biden administration aims to reduce the mortality rate from cancer by 50% over the next 25 years and “improve the experience of people and their families living with and surviving cancer.”
“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. All of these are tenets of Cancer Moonshot’s mission,” Richard Pazdur, MD, director of FDA’s Oncology Center for Excellence, stated in a press release.
Including older adults in cancer trials
The final guidance for FDA’s document on including adults 65 years and older in cancer trials offers recommendations for stakeholders like sponsors and institutional review boards. One major focus of the guidance is the importance of enrolling these patients in early phase trials to gather information for later trial phases, and to examine potential drug-drug interactions to limit trial exclusion in this patient population. The guidance also elaborates on how to design trials, strategies for recruitment, collecting information for enrollment of older adults in cancer trials. (RELATED: FDA Encourages Inclusion of Older Patients in Cancer Trials, Regulatory Focus 09 March 2020)
“It is vital to have older adult patients in clinical trials because differences may exist between younger and older patients in drug response and toxicity,” FDA said. “Older adults often have other diseases or conditions and may be taking medications that could impact the efficacy of either the cancer drug or other drugs they are taking and may also impact the incidence and the severity of adverse events. There could also be important differences in efficacy in older adult patients compared to the younger or general population.”
FDA made a few changes between the draft guidance issued in March 2020 and the current final guidance. “Changes from the draft to the final guidance include capture of comorbidity information, clarification that this guidance applies to both small and large studies, added guidance on decentralization and recruitment efforts for community oncologists, an improved definition of adequate representation in a study trial, clarification of trial design stratification, and added references to other guidances,” FDA wrote in a Federal Register notice.
FIH cancer trials with expansion cohorts
The final guidance on expansion cohorts for FIH trials to expedite oncology drug and biologic development, intended for industry, describes the agency’s thinking on how sponsors would design FIH trials for expedited drugs as well as the challenges stakeholders might encounter along the way. Specifically, the guidance explains how stakeholders could recruit patients across different expansion cohorts “to assess many different aspects of a drug in a single clinical trial to efficiently expedite the clinical development of the drug,” the agency said.
FDA’s final guidance also includes information on what kinds of drugs would work best in trials with multiple expansion cohorts, what information stakeholders should provide in investigational new drug applications for trials involving expansion cohorts, patient safeguards for trials, and under what circumstances stakeholders should work with FDA on studies with multiple expansion cohorts. (RELATED: FDA Drafts Guidance on Seamless Clinical Trials for Cancer Drug Developers, Regulatory Focus 10 August 2018)
In response to the draft guidance issued in August 2018, industry proposed several changes to the detail and scope of the guidance for the final version (RELATED: Industry Proposes Changes to FDA’s FIH Expansion Cohort Guidance, Regulatory Focus 16 October 2018). FDA wrote in a Federal Register notice their final guidance clarifies that stakeholders evaluating antitumor activity in a non-randomized cohort could use either a Simon two-stage trial design or another design to reduce the likelihood participants are receiving an ineffective treatment. Other changes to the final guidance include changes to what kinds of drugs are ideal for a multiple expansion cohort, an addition that recognizes pediatric populations may need an age-appropriate formulation, and a note that the sponsor can use a safety assessment committee inside their own organization instead of an independent data monitoring committee if a trial has a limited sample size and the internal committee is not involved with the trial.
Master protocol trial design strategies
FDA’s final guidance on efficient trial design for expedited development of drugs and biologics in oncology offers advice on master protocol design as well as what FDA wants from sponsors to execute the trial design, and how to work with FDA in an efficient review process. The agency also highlighted challenges of implementing trials with master protocol designs, including the difficulty of attributing adverse events in trials evaluating multiple oncology treatments or multiple patient populations under one master protocol. (RELATED: Clinical Trials: FDA Releases Two Draft Guidances, Regulatory Focus 28 September 2018)
In a Federal Register notice, FDA said they revised portions of the final guidance from the draft guidance with clarification on what sponsors should give FDA when supporting amendments requesting a protocol expansions as well as “information about a dose-finding or safety lead-in component in basket trials when evaluating an investigational drug combination and comparison between experimental arms in umbrella trials and acceptable statistical approaches.”
“The standard approach to generating evidence has become more expensive and challenging to execute and, as a result, answers to important clinical questions are often delayed,” FDA said. “Well-designed master protocols can provide answers more quickly and efficiently than traditional clinical trials. Because of the complexity of these trials and the potential regulatory impact, it’s important that the FDA is providing this guidance on how to conduct well designed trials that protect patient safety and obtain quality data needed to support drug approval.”
Inclusion of Older Adults in Cancer Clinical Trials
Expansion Cohorts: Use in First-in-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics
Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics


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