In the time since we last met for the American Society of Clinical Oncology (ASCO) congress, much has changed in the world of cancer research and clinical development. 2018 was a record-breaking year with 59 FDA approvals overall; of these, there were 19 FDA approvals of new cancer drugs, as well as further approval of 38 medicines in supplemental indications, and 4 biosimilars. Our Jim Wise explores some of the changes over the past 12 months:
- The FDA accelerated approval of larotrectinib (VITRAKVI) in both adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion (hybrid gene from two which were formerly separate) without a known acquired resistance, marked the second tissue/tumor-agnostic (a drug used to treat any cancer indication, regardless of bodily location and tissue from which it developed, as opposed to a treatment developed to treat a specific type of organ or tissue) FDA approval for the treatment of cancer.
- Additional forward motion in the area of tissue/tumor-agnostic drug development includes the use of pembrolizumab (KEYTRUDA), the first tumor-agnostic FDA approval, in a number of indications. This was first approved in non-small cell lung cancer (NSCLC) in February 2015 but has received approval to treat several other indications, for example, melanoma and renal cell carcinoma in February and April 2019 respectively. A tumor-agnostic drug targets any kind of cancer as long as the cancer has the specific molecular mutation targeted by the compound. This continues to hold promise in other areas such as cancers of the bladder, breast, gastric cancers, and hematologic malignancies.
- As well as landmark approvals, the FDA has also developed two new endpoints. In November 2018 the FDA issued a draft guidance recommending metastasis-free survival (MFS) as an endpoint in trials for non-metastatic castration-resistant prostate cancer (nmCRPC). MFS is defined as a significant prolonged delay in the development of metastatic disease as an objective and clinically relevant outcome. This endpoint was used in the approval of apalutamide (Erleada) for nmCRPC in February 2018, prior to this approval there were no medications specifically available to treat this indication.
- October 2018 saw the FDA make available draft guidance for industry titled Hematologic Malignancies: Regulatory Considerations for Use of Minimal Residual Disease (MRD) in Development of Drug and Biological Products for Treatment. MRD is a biomarker measuring the residual cells remaining post treatment and was used as an endpoint for the approval of blinatumomab for B cell-precursor acute lymphoblastic leukemia.
- Real-Time Oncology Review (RTOR), an FDA pilot review program is also being utilized to explore an efficient review process to ensure safe and effective treatments are made available to patients as quickly as possible while maintaining quality and integrity of data. While this pilot has no definite timeline and specific criteria has to be met to qualify for the program, it has already been tested through a number of pilot programs for supplemental indication approval since its 2018 launch and will likely expand to new drugs and biologics having demonstrated efficiency. For example, Kisqali (ribociclib) was approved for breast cancer in late July 2018 (having originally been approved in 2017) just one month after its submission for an additional indication. Owing to RTOR, the FDA was able to begin its analysis of data prior to submission and to guide the applicant in presenting the most relevant data. In March 2019 the seventh product was reported to be navigating the RTOR program, showing huge promise for speedily bringing life-saving medications to patients.
- Research efforts are a global endeavor and breakthroughs are being made in all regions. For example, in August 2018 scientists in Melbourne, Australia found a new class of anti-cancer drug focusing on KAT6A and KAT6B proteins that is able to put malignant cells into a permanent “sleep,” without the DNA damage or any of the detrimental side-effects that can be experienced by patients using more conventional cancer therapeutics. This new strategy is now showing encouraging results in preclinical research.
- In the same month Chinese scientists undertook the first experiment using gene technology to delete HUWE1, the gene thought to be responsible for lung cancer, and while this research is still in the laboratory stages it clearly demonstrated the genes role in development of lung cancer and may help with future therapeutic targets.
- A small team of Israeli scientists reported in January 2019 that they were working on a project called “MuTaTo” (multi-target toxin), these researchers claimed the drug would essentially be "on the scale of a cancer antibiotic - a disruption technology of the highest order.” While there is not yet any published research on the topic and clinical trials will not begin immediately, the use of highly specific cancer-targeting peptides may offer excellent alternative targeting agents for cancers.
Looking forward and to ASCO’s 2019 congress, we will see streams focused upon more of the extraordinary progress the scientific community continues to contribute toward the prevention, diagnosis, and treatment of cancers, with particular interest in the continued progression in such fields as immunotherapy, targeted therapies, molecular diagnostics, rare cancers (ASCO notes 5 studies which significantly marked progress in this area recently in its 2019 clinical advances report), and microbiome research.
Optimal Recruitment Strategies
A mid-size, top 5 European pharmaceutical company engaged PRA in a global Phase III study in 20 countries on patients with advanced breast cancer…
Data Monitoring Committee Unit
Due to increasing regulatory requirements, the need for quality study and patient safety data is critical as we work together to bring our clients’…