FDA Issues New Clinical Trial Guidelines to Further Cancer Therapy Development

Richard Pazdur, MD

The FDA released 3 new recommendations for industry to support and expand President Joe Biden’s 2016 Cancer Moonshot initiative. The new guidelines reflect improvements in medical science over the past 6 years and are designed to facilitate continued advancement in cancer prevention, detection, research, and patient care.¹

Biden’s updated targets call for reducing the death rate from cancer by at least 50% over the next 25 years and improving the experience of people and their families living with and surviving cancer. The president’s ultimate goal is to “end cancer as we know it today,” according to a press release issued by the FDA.

“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,” Richard Pazdur, MD, director for the FDA’s Oncology Center for Excellence and the 2019 winner of the OncLive^® Giants of Cancer Care^® award for community outreach, education, and cancer policy, stated in a news release. “All of these are tenets of Cancer Moonshot’s mission.”

The first guidance, titled “Inclusion of Older Adults in Cancer Clinical Trials,” provides recommendations for entities responsible for the development and oversight of clinical trials for cancer drugs, including sponsors and institutional review boards. The FDA noted that older patients are underrepresented in clinical trials despite representing a growing segment of patients with cancer. The agency stressed the importance of including adults aged 75 years and older in cancer clinical trials.²

The guidance includes procedures for including older adults in research related to early clinical development, including trial design and recruitment. The agency also calls on trial designers to develop and report discrete age subgroups and to include older adults in post-market research.

“Enrolling an adequate representation of the range of patients in a clinical trial that may be exposed to a drug after approval can maximize the generalizability of the trial results,” the agency wrote. “It provides the ability to understand the drug’s benefit-risk profile across the patient population likely to use the drug in clinical practice. Including information in the labeling describing use in older adults helps to promote the safe and effective use of these products and better informs treatment decisions in clinical practice.”

The second guidance, “Expansion Cohorts: Use in First-in-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics,” focuses on early-stage drug development. Here, the FDA provided advice 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.³

The FDA provided recommendations on:

1. Identifying drug products best suited for multiple expansion cohort trials
2. Including the correct supporting information for investigational new drug application submissions
3. Consulting with the agency on trial planning and conduct studies
4. Protecting trial participants

The final guidance is titled, “Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics.” Master protocols use a single infrastructure, trial design, and protocol to simultaneously evaluate multiple drugs and/or disease populations in multiple substudies.

Here, the FDA shared advice on the design and conduct of clinical trials, other than first-in-human trials, that simultaneously assess more than 1 investigational drug and/or more than 1 cancer type within the same overall trial structure.⁴

“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,” the agency wrote. “Well-designed master protocols can provide answers more quickly and efficiently than traditional clinical trials.”

References

1. FDA clinical trial guidances share Biden Administration’s goals for advancing development of cancer treatments. News release. FDA; March 1, 2022. Accessed March 1, 2022. https://bit.ly/3sxyQoI
2. FDA. Inclusion of older adults in cancer clinical trials; guidance for industry. March 1, 2022. Accessed March 1, 2022. https://bit.ly/3ICjO6F
3. FDA. Expansion cohorts: use in first-in-human clinical trials to expedite development ofoncology drugs and biologics; guidance for industry. March 1, 2022. Accessed March 1, 2022. https://bit.ly/3hM8E3H
4. FDA. Master protocols: efficient clinical trial design strategies to expedite development of oncology drugs and biologics; guidance for industry. March 1, 2022. Accessed March 1, 2022. https://bit.ly/3sxHovJ