Due to a recent surge in new oncology drugs entering the market, standards of cancer care are shifting at a quickening pace, leading some pharma companies to react to these changes mid-development. For instance, if a pharma company has a drug in clinical trials, but a competitor beats them to market, what do they do?
 
In this Q&A, we spoke with Andrew Zupnick, Ph.D., Vice President, Oncology Strategy of Novella Clinical to provide insights into the factors behind the rapid pace of new drug approvals, the implications for pharma companies in this crowded field, and how they can succeed in this hyper-competitive landscape.

Contract Pharma: What do you attribute to so many new drugs being approved?
 
Andrew Zupnick: We are currently in an era where our understanding of the biology behind cancer has aligned with improvements in technology to help spur the development of smarter therapies that can specifically target cancer. Connected to that, regulatory agencies have encouraged accelerated development pathways which allow for a shorter time to market for truly breakthrough therapies. As a result, we are seeing a tremendous wave of oncology drug approvals, with many of them producing unprecedented treatment success.
 
There are approximately 800 cancer drugs in development today and over 12,000 active cancer clinical trials. It’s thrilling that these promising new therapies have potential to change the course of cancer treatment and drastically improve lives. For example, we have much more affordable, sophisticated technology for tumor imaging and genomic sequencing. It is now possible to personalize cancer patient treatment based on the patient’s cancer biomarkers rather than simply the tissue of origin. We are also seeing significant progress being made with immunotherapy, which capitalizes on the immune system’s ability to recognize and destroy cancer cells.
 
CP: How has the drug approval process changed in light of these new therapies?
 
AZ: Well,the FDA has greatly accelerated approval timelines for therapies that may confer a significant benefit or address a particularly unmet need. In 2014, all but one FDA-approved oncology drug followed some form of expedited pathway. One year later, the FDA approved more oncology drugs than ever before. The rapid rate of cancer drug approvals has in turn accelerated changes to the standard of care. Emerging clinical data continues to shape the way physicians treat patients with cancer as well; for example, the National Comprehensive Cancer Network has revised its clinical practice guidelines for lung cancer five times since they were first issued in late 2016.
 
Another thing that has changed is the acceptance of surrogate endpoints. Instead of relying solely on overall survival to demonstrate a drug’s safety and effectiveness in clinical trials, the FDA has become more willing to accept surrogate endpoints that weigh response and the duration of response for initial approval. In the case of targeted cancer therapies, toxicities are often well tolerated since the drugs are designed to hone in on cancer cells specifically (versus the case with chemotherapy where all cells that multiply are targeted), patients are receiving multiple lines of therapy to keep cancer at bay longer, and more metrics are used to determine clinical efficacy.  In the case of immunotherapies, toxicities can be extreme as the immune system is being engaged, and are still a risk which needs to be monitored closely, but the benefits can significantly outweigh the risk (as evidenced by the recent FDA ODAC discussion on a landmark autologous T-cell therapy).
 
It has become common for the FDA to approve drugs based on single-arm cohorts of larger Phase 1 or Phase 2 trials versus the traditional Phase 1-3 development process. Earlier this year, for example, the FDA approved the bladder cancer immunotherapy Imfinzi™ (durvalumab) following a 182-patient single-arm bladder cancer cohort from a larger Phase 1/2 multi-arm trial.
 
CP: What does that mean for pharma companies?
 
AZ: Both the scientific promise of novel therapies and the FDA’s enthusiasm to speed up the review process make this a truly exciting time for pharma companies. The good news is drug developers can move through the review process quickly and clinical development timelines can be shortened, bringing the latest drugs into physicians’ and patients’ hands faster than previously seen. But amidst an evolving landscape, it can be challenging for sponsors to plan clinical trials that keep up with the latest changes to standard of care, or even anticipate future shifts to the competitive landscape while their trial is enrolling.
 
CP: What can pharma companies do to account for these changes in standard of care during their clinical trials?
 
AZ: No one can predict the future; sponsors can only use the information available to anticipate which treatments are going to be approved while their trial is in progress. A safer bet, therefore, would be to design clinical trial protocols with a degree of flexibility.
 
There are a couple of ways to go about this. For one, sponsors can speed up patient recruitment by making the language in inclusion/exclusion criteria less strict. The drawback is that a more heterogeneous population may present complications to data quality and statistical efficacy.
 
In trials where an investigational drug is paired or compared with an existing standard of care, and that standard may change, an option is to leave it “investigator’s choice,” whereby they can choose from a list of comparators that have a similar mechanism of action.
 
Another way to stay ahead of changes is to account for them in the study design. Sponsors prefer to avoid making critical amendments to their protocols because they can be time-consuming and expensive, but in reality, changes are going to occur. Plan as much as you can in advance and remain open to making changes if they become necessary.
 
And last, but not least, many drug developers are conducting multiple-arm trials. We recently worked with one that pivoted its trial to include their drug as a second-line therapy after noticing a competitor was closer to first-line approval. We like this strategy because it filled an unmet need in treatment as approved second-line therapies are minimal. This also eliminates the need to compete for the same group of patients, and speeds the potential time-to-market. Plus, the drug can still compete head-to-head against the first-line therapy later.

These are just some strategies for conducting clinical trials that we have seen help companies bring new cancer therapies to market successfully in this rapidly changing treatment landscape.