Over the past two decades, the treatment of cancer has undergone a transformation. Advances in the characterization of cancer progression and molecular biomarkers have translated into new therapies—and even new classes of therapies, including immune checkpoint inhibitors and cell therapies.
Much of the credit goes, deservedly, to pharmaceutical and biotechnology companies, as well as to cancer research centers, which help advance drug development. Without efficient and accurate trials, candidate therapies cannot gain rapid and widespread approval. If those collaborations are so vital, what are the hallmarks of successful ones?
Taking an active approach
As co-chief medical oncologist of the thoracic division at John Theurer Cancer Center (JTCC) at Hackensack University Medical Center, I lead our experimental drugs research program, which aims to keep JTCC at the forefront of immunotherapy research. After decades developing research collaborations, I’ve seen that most are initiated by drug companies that recruit institutions as partners. But, that outreach need not always flow in one direction. My institution is proof that when cancer research centers collaborate with pharmaceutical industry partners, the results can be just as good, if not better.
In my capacity at JTCC, I spend a lot of time searching for promising early-stage compounds and exploring possible clinical trials with their developers. Many of those discussions lead to successful research partnerships. For example, along with other institutions, we completed a Phase 1/2a study of a novel OX40 agonist, the results of which were published last year in .
We also actively seek trials that we expect will advance the field, and serve our patients. At JTCC, we pursue industry-institutional partnerships that operate at the interface between pre-clinical workor in animal models and first-in-human trials. That position allows us to identify novel, first-in-class agents directed at known therapeutic targets, but for which the safety, pharmacokinetics, and appropriate dosing in humans need to be characterized. We find this balance tends to maximize the benefit to our patients, many of whom have few other treatment options.
Seeking first-in-class candidates
One of the most urgent questions in oncology is how to overcome immunological resistance in tumors. How solid cancers develop resistance is complex, but the question has spurred investigation into a number of novel approaches, including cancer vaccines, intratumoral injections, and cellular therapies that prime the immune system to overcome resistance.
Researchers are currently investigating chimeric antigen receptor T cell (CAR-T) therapy, natural killer (NK) cells, and various types of autologous and allogeneic cells as potential immune-priming strategies. Of about 20 actively enrolling clinical studies we are conducting at JTCC, as well as the 12 to 15 new studies we open in a typical year, roughly 30% focus on the use of cell technologies to prime the immune system.
In addition, JTCC typically has about 30% active trials of therapies directed against well-characterized targets such as KRAS, PD-1, PD-L1, or the fibroblast growth factor receptor (FGFR). Several years ago we developed the Phase 1 protocol for pemigatinib (INCB054828), one of the first FGFR inhibitors to enter the clinic; this agent is now approved for the treatment of cholangiocarcinoma. Before that, we were among the first research centers to conduct Phase 1 studies of nivolumab, the first PD-1 inhibitor to reach the clinic, in hematologic malignancies, and similarly investigated the PD-L1 checkpoint inhibitor, durvalumab, from the very beginning of its clinical development.
Establishing robust selection criteria
Having a novel mechanism of action is no guarantee of clinical success for an anticancer treatment, making it especially important to select therapeutic candidates carefully. At JTCC, when we identify an agent with promising preclinical data, we first ask if the target is biologically sound and whether it is validated as part of an important oncologic pathway. We also ask whether the agent has demonstrated efficacy in animal models and preclinical toxicology data. Does it show the toxicity in animals is tolerable, and what are the chances that will translate to humans?
Favorable answers to those questions can help map out the future development pathway for an investigational agent, including potential disease indications.
Partnering with industry
When I started at JTCC in 2012, I spent a lot of time knocking on the doors of potential industry partners to see which ones would allow us to participate in their drug development programs. As JTCC has developed a reputation for efficiently executing clinical trials, our roster of studies has grown, as have our relationships with smaller biotech companies.
Our industry collaborations have now developed to the point that they are bi-directional. Just as we reach out to potential industry partners, we now have companies contacting us. By developing close personal relationships with our partners, we can provide input into study protocols and IND submissions, while also facilitating contract and budget negotiations as well as interactions with institutional review boards (IRBs).
Our relationship with Bristol-Myers Squibb (BMS), the developer of the novel OX40 agonist BMS-986178, is a case in point. The data suggests that BMS-986178 might address some of the limitations of checkpoint inhibitor therapy.
Based on that success, we are now working with BMS to explore research collaborations for nearly a dozen investigational therapies in the company’s pipeline.
Building a model that benefits everyone
After more than 20 years working in drug development, holding positions in government, private practice and academia, I view JTCC as unique in its ability to build one-to-one relationships with both partners and patients. Our research collaborations focus on delivering therapeutic opportunities to patients that lack other options.
While we at JTCC will continue to seek partnerships that advance these goals, our hope is that other centers consider a similar model. If the ultimate goal for everyone in the drug development ecosystem is the safe and rapid rollout of effective, new therapies, then a strategic and bi-directional approach to partnerships should be step number one.