Immunotherapy’s Spotlight Grows Even Brighter; FDA Makes Clinical Trials More Efficient

Novella Clinical looks back at the biggest oncology news of 2018

A New Generation of Cancer Treatments

Last year, the American Society of Clinical Oncology (ASCO) named chimeric antigen receptor (CAR) T-cell therapy as its “Advance of the Year.” CAR-T technologies modify patient-specific or ‘off the shelf’ T-cells to seek and destroy cancer cells, and unlike most cancer treatments, this therapy is typically only given once. This is because these T-cells, once administered, multiply in the body and persist as part of a targeted and rejuvenated immune system. Already, oncologists are seeing these T-cells produce remarkable results in children and young adults with acute lymphoblastic leukemia (ALL), and in adults with hard-to-treat lymphoma and multiple myeloma. More CAR-T therapies are on their way.

This innovative therapy wouldn’t exist without the momentum generated in immuno-oncology (IO) by our knowledge of immune checkpoints and how to block them, the discovery of which earned Dr. James Allison and Dr. Tasuku Honjo the Nobel Prize in physiology and medicine this year. Immune checkpoints naturally prevent the immune system from targeting tumors. Understanding how to block them has opened the floodgates to a multitude of targeted immunotherapies for cancer. For example, last year, the FDA granted an accelerated approval to nivolumab (Opdivo®) for third-line treatment of metastatic small cell lung cancer, and approved cemiplimab-rwlc (Libtayo®) as the first immunotherapy for cutaneous squamous cell carcinoma, the second most common form of skin cancer.

Scientists also took a big step this year in developing personalized treatment strategies for patients with relapsed or refractory multiple myeloma based on a computation platform using DNA and RNA biomarkers as inputs. By identifying and analyzing hundreds of actionable mutations in dozens of patients in several genes, researchers were able to derive treatment recommendations for 98 percent of the patients.

The FDA paves the way for more efficient oncology drug development

Connected to the success of immunotherapies, the FDA has made several regulatory changes that make the process of developing breakthrough therapies more efficient, such as modernizing clinical trials, streamlining the FDA’s organization and processes to advance regulatory science, and expanding the FDA’s capacity to analyze complex real-world data streams to detect early safety and efficacy signals. This has already surpassed their prior record of 53 new molecular entity (NME) approvals set in 1996.  With accelerated approvals though come the risk of underdeveloped safety or efficacy profiles that evolve as more data becomes available. For example, based on confirmatory data that was worse than expected, the FDA updated the prescribing information for the immunotherapies pembrolizumab (Keytruda®) and atezolizumab (Tecentriq®) for the treatment of patients with locally advanced or metastatic urothelial cancer to require the use of an FDA-approved companion diagnostic test to help identify patients who are most likely to benefit from these checkpoint inhibitors.

Further to the FDA’s commitment to expediting the approval of novel therapies, 2018 saw the launch of the Real-Time Oncology Review and Assessment Aid programs in an effort to speed development. Real-Time Oncology Review enables the FDA to review clinical trial results as soon as they’re available, prior to receiving a formal application from the sponsor. The FDA’s Assessment Aid is a new template that allows sponsor and FDA conclusions about drug efficacy and safety to be integrated into one structured form. This will help improve consistency, decrease review time spent on administrative tasks, such as formatting, and allow the FDA to focus on critical thinking and assessment.

Finally, in another effort to improve development efficiency, the FDA released draft guidance supporting the use of multiple expansion cohorts as an alternative to the traditional clinical trial designs. Multiple expansion cohort trials enable sponsors who spot strong, positive responses to an investigational drug during early stages of testing to expand the trial using additional single-arm studies to gather pivotal data more quickly and speed the drug’s path to approval. This gives sponsors the flexibility to optimize their trial design on an ongoing basis to maximize their chances of success. The FDA advises that these trials only be used for select patient populations for whom the benefits outweigh the risks and there are no curative therapies available. If you’d like to learn more about this new pathway, Novella has created a whitepaper on this topic, including how a seamless clinical trial strategy requires a different mindset than traditional pathways.

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