New Operational Methods Emerge in Cancer Clinical Trials

Emerging areas in cancer clinical research pose new challenges in the small biotech industry. However, some enterprises are efficiently navigating their clinical trials by incorporating novel strategies, including the incorporation of analytics, to expand clinical trial access to patients who need it. In this interview, Vanessa Tassell, Vice President, Clinical Operations at Mirati Therapeutics, will discuss her experience in this rapidly evolving field.

Moe Alsumidaie: Mirati is progressing to a precision oncology pipeline, focused on hard-to-treat cancers in innovative ways, including targeting KRAS mutations. Considering that KRAS is known for being hard to target with drug treatments, can you talk about the challenges Mirati experienced, how those challenges shaped Mirati’s guiding principles with clinical trial program design, and how you targeted this pathway?

Vanessa Tassell

Vanessa Tassell: As you know, Mirati was founded in 2013, and since then, we’ve pursued the most challenging mutations for our trial designs, like KRASG12C. Part of our investigational programs are looking at the most difficult-to-treat cancers, like lung, colon, and others. Our guiding principles are focused on the patients first and foremost. We also are guided by the analytics, the clinical trial design, education for our clinical trial sites/investigators, and partnerships. It is essential to work closely with our partnered molecular labs to assess the feasibility of testing to place our clinical sites in suitable locations. That is critical for understanding how to bring our clinical trials to the locations where patients are being tested. Are they academic centers? Are they community-based centers?

We also look at what we need to do to help bring education, especially to the community-based centers, for early-stage trials. Education is essential when it comes to that, and partnering with and understanding the needs of those centers is critical to our success—and again, focusing on the needs of the patients, their families and designing the trials in a way where access is a primary focus.

MA: Please describe your analytics strategy in site selection.

VT: We partner with several molecular labs to find where these patients are being tested. For our U.S. and our global trials, we need to understand our investigators’ treatment patterns and how we can bring more testing to those centers to give patients access to our clinical trials. So the analytics are based on our close partnerships and getting data to target those locations and specialty community centers to connect patients with our clinical trials. 

MA: What has Mirati done differently with its studies to ensure not only continued advancements in clinical development but also to serve the patients who guide your work?

VT: The science that we pursue is looking at novel mechanisms and combination strategies that the patients don’t have access to. Again, going back to partnering with key opinion leaders, we look to see where we can optimize our clinical trial design to make it easy for patients to access our clinical trials. It goes back to where the testing is being conducted and how we can train sites to get early testing for early-stage trials. As a biotech, we are nimble, but we also have the internal experience of large pharma in our leadership. It’s the best of both worlds when it comes to trial design, as well as a strategy for our clinical trial programs.

Key opinion leaders bring much experience to the table as part of our think tank-type model, and we have been working with them from the beginning at Mirati. Many of us have had experience with many of these investigators through prior companies as well. Collaborating is very critical for us to understand what’s happening in the field. Our current collaboration with MD Anderson is a good example. We work with several investigators who bring their ideas to the table to look at additional novel combinations that will continuously extend our clinical programs.

MA: Mirati has gone from a single asset company to a company with many assets in its pipeline over the past few years. What sorts of changes are you starting to implement to prepare for scaling clinical research and clinical operations?

VT: We have had incredible progress with our pipeline. I’ve been with the company for eight years, so I’ve seen it go from a single asset to a multi-asset company. We have two clinical-stage assets that both have registration trials currently. We also have two potential first-in-class preclinical programs: a KRASG12D inhibitor and the synthetic lethal PRMT5 inhibitor. Working with key opinion leaders, who hold a strong belief in our science, has helped us because we can go back to these think tanks to support us with the best design options and understand the capabilities of these novel designs to where we can get patients access.

We’re also very fortunate to have an in-house research group with discovery capabilities working closely with our clinical development colleagues. We have this constant pipeline of candidates to build the infrastructure needed to have a late-stage company and a company that can focus on Investigational New Drugs (INDs). We have built those efficiencies over time, and as we’ve grown, those competencies have grown.

MA: Can you tell me a bit about the differences between an early-phase versus a late-phase type of infrastructure? Are you vertically integrating and bringing some of those tasks internally versus outsourcing?

VT: We have first-in-human studies to large Phase III programs. We have a variety of vendors that we work with to optimize our internal infrastructure and use different service providers to help us scale to what we need, not only in the U.S. but globally. We’ll continue to work in this fashion to build the infrastructure to support our pipeline.

MA: Could you tell me how headquartering in San Diego helped to advance clinical trial programs and what benefit this location provides to Mirati?

VT: San Diego is an excellent hub for innovation and key for continuing our collaborations and partnerships with key opinion leaders and community-based centers. We’ve recently moved into a large facility in Torrey Pines, where we have our integrated team, including dedicated scientists who will continue to push forward our pipeline. As a biotech hub, it’s an excellent location for talent and a great place to attract talent from other locations. Being in San Diego has helped continue our collaboration and our innovation.

MA: Among the standard obstacles encountered during clinical trials, Mirati had the added challenge of conducting clinical trials within a pandemic. Can you tell me a bit about how COVID-19 impacted the clinical trials for a smaller biotech company like Mirati, and what strategies have you leveraged to navigate this environment?

VT: Being a science-based company, it was vital for us to focus on the safety of the patients and the staff who were part of our clinical trial program. We worked very closely with the clinical sites to understand their institutional policies and practices and with our vendors to help support the changing landscape. Part of this was understanding how we could be flexible in our clinical trials, follow industry regulations, and establish new processes to allow for flexibility for our patients. We would work with the clinical sites and provide them with flexibility when it came to scheduling patient visits, ensuring that we were supporting them as much as possible to help them accommodate patients.

We modified our protocols; we gave allowance for flexibility. We supported updated procedures at our core vendors to ensure that we could do a decentralized data review. We didn’t skip a beat to ensure that we reviewed clinical data, specifically safety data, and ensured that our patients could stay on the study. Again, focusing on making sure that we were partnering with clinical sites to understand what they could do to help us limit the negative impact on our trial recruitment and continue to add clinical trial sites, which was critical globally. It was essential to partner with our vendors and clinical sites to ensure that we followed regulations and kept patients’ safety in mind.

MA: So, how do you see things moving forward regarding the pandemic and in this new environment that we operate in?

VT: I think we need to keep our eyes wide open. We need to continue thinking about how we can optimize our clinical trial designs to ensure flexibility. It will be critical to look for processes and technologies that ensure patients can continue to be seen and that sites can continue to access what is needed for their patients. The industry needs to take this very seriously since this will continue to be part of trial design and strategy moving forward. This continuous flexibility will be required to keep patients safe and give them access to clinical trials.

Moe Alsumidaie, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.