According to data from BioTracker, the probability of an oncology candidate moving from phase 1 to regulatory approval is only 5%—the lowest rate of success among all therapeutic areas. At the high end, hematology drugs have a 26% likelihood of approval—not exactly a good batting average.
If a drug does make it to phase 3, overall success rates improve, but they are still frustratingly low. In the case of oncology drugs that make it to phase 3, the likelihood of FDA approval is still only 39%.
As daunting as these statistics may seem, there are initiatives underway to make oncology clinical trials more efficient and more likely to succeed. Many in the space agree that innovative clinical trial design in the oncology space is the key to improving the success rate for oncology drug candidates.
In addition, designing clinical trials to be more efficient can also contribute to lower overall development costs and faster approval times.
This was the starting point for a conversation between moderator Ellen V. Sigal, PhD, Chairperson and Founder, Friends of Cancer Research, and four panelists—from Bristol-Myers Squibb (BMS), ICON plc, Rgenix and Montefiore Medical Center—during a BIO CEO 2016 therapeutic session focused on improving oncology clinical trials.
Biomarkers, immunotherapy, next-gene sequencing, and big-data analysis
To start, there was a full-throated consensus that the ongoing discovery and validation of biomarkers is the key to unlocking better outcomes and advancing the science. “Having well-validated biomarkers in a clinical trial improves the likelihood of success four-fold,” said Sigal.
Panelist Paul Biondi, Senior Vice President and Head of Business Development at BMS, expressed his excitement about the long-term promise of immuno-oncology and the early successes of the currently available immunotherapies, including BMS’s superstar immuno-oncology drug, Opdivo (nivolumab).
On the upside, Biondi noted that BMS has entered into numerous collaborative research partnerships with smaller biotech companies looking to test their oncology candidates using Opdivo as a backbone. "We are also doing a lot of investigator-sponsored research," he added. "There’s a tremendous amount of innovation in the ecosystem."
However, Biondi’s enthusiasm was tempered by his concern that there are too many unanswered questions—big issues that need to be addressed to maximize the tremendous untapped opportunities associated with this class of compounds.
Immunotherapy is still evolving
"There’s a lot we need to learn," said Biondi. "We need stronger signals for certain solid tumors, such as breast and prostate cancer. With immunotherapy, a lot of traditional endpoints aren’t that relevant. We need more novel endpoints and surrogates for survival."
Another challenge related to immunotherapy trials is developing next-generation sequencing methods that can be used to develop immuno-oncologic drugs, according to panelist Dr. Eric Rowinsky, President of Rgenix.
There’s also the issue of how to use all of the data from all of the clinical trials taking place. "We have to figure out how we can best analyze all of the data we’re getting," said Andreas Draps, Senior Vice President and Global Head of Drug Development at ICON. "We have to come up with more innovative ways to analyze the data and apply the learnings."
Noteworthy improvements on the regulatory front
While the regulatory structure for getting drugs approved is far from perfect, the panelists agreed that the FDA has become more flexible and more supportive of innovative approaches to clinical trials.
For example, Rowinsky noted that expanded phase 1 trials give investigators a chance to learn, with additional time to optimize the trial and accrue the appropriate patients before moving to phase 2.
Expanded phase 1 trials also make it easier for investigators to look for early signs of clinical efficacy. When there are early signs of clinical efficacy, a company can then pursue a breakthrough designation, which can expedite the approval process.
On the flip side, certain signals can also help a company decide to halt the trial and cut its losses early.
Examples of innovative clinical trials
Sigal identified two recently launched oncology trials which incorporate many of the elements of precision medicine with innovative design techniques. The NCI-Match (Molecular Analysis for Therapy Choice) trial, which is being spearheaded by panelist Dr. Joseph Sparano, an oncologist at Montefiore Medical Center in New York, is designed with all of the elements of President Obama’s Precision Medicine Initiative.
NCI-MATCH has an ambitious purview. It was designed to test more than 20 targeted cancer drugs in genomically profiled patients with advanced solid-tumor cancers or lymphomas that no longer respond to treatment. Because genomic profiling is part of the study, patients are assigned to a drug regimen that targets their cancer’s genetic mutations.
There are two primary endpoints of NCI-MATCH—overall response rates and six-month progression-free survival, with researchers looking for a target response rate of at least 16% to 25% in order to consider a treatment potentially effective.
NCI-MATCH is a large-scale trial, but its innovative design and methodology focus on personalizing treatment, which ultimately saves time and money, and will hopefully save many patients’ lives.
Another example of innovative trial design, Lung-MAP, is a public-private partnership involving the National Institutes of Health (NIH), the National Cancer Institute (NCI), and a host of pharmaceutical companies (Amgen, Genentech, Pfizer, AstraZeneca, and MedImmune).
Lung-MAP uses targeted screening to match patients who have squamous cell lung cancer with clinical trials designed to evaluate various investigational and approved drugs against a vast array of genomic targets.
"This trial is different from most trials, because it allows all comers to enroll and because of the unprecedented level of the public-private partnership collaboration," said Sigal.
Panelists weigh in on Cancer MoonShot 2020
Cancer MoonShot 2020 was a popular topic at the BIO CEO conference because it embodies the collective ambitions of the private and public sectors. However, as invested as companies and researchers involved in oncology research are in the goals of the initiative, there are serious hurdles to overcome.
When Sigal asked the panelists to discuss key challenges that must be overcome in order for Cancer MoonShot 2020 to be successful, Sparano, who has decades of experience in oncology research, identified three key challenges that need to be addressed.
First, he noted the need for better short- and intermediate-term endpoints defined by specific pharmacodynamic biomarkers. He also pointed to the need to continue to address regulatory challenges head on—meaning make clinical trials more efficient, with an eye towards even more flexibility.
Finally, Sparano brought the conversation back to the patient. "We need to do a better job of making participation in cancer trials part of the culture of cancer care," he said.