AbbVie’s Head of Oncology Precision Medicine on the Exciting Developments in Immuno-Oncology
Dr Raluca Verona, Head, Oncology Precision Medicine Group at AbbVie, tells us how she is helping to advance the immuno-oncology field, and the power of real-world data, ADCs and T cell engagers for the next phase of cancer treatment.
What is your responsibility as Head of Precision Medicine Oncology at AbbVie?
As the head of Precision Medicine Oncology at AbbVie, I lead a team of clinical biomarker and translational research scientists. We leverage strong scientific insights and data to guide and accelerate the advancement of AbbVie’s oncology therapeutics from late discovery through early and late clinical development.
One key goal for us in Precision Medicine is to optimize ways to select the right patients for our drugs. We do this by identifying predictive biomarkers that may help tailor a therapy to the genetic, molecular or immune profiles of cancer patients. This approach is critical to optimize the efficacy and potentially improve outcomes for patients.
What can you share about your recent work in biomarkers and precision medicine?
Our Oncology portfolio at AbbVie spans across heme malignancies and solid tumors and a number of modalities, including multispecifics and a growing portfolio of ADCs. In the Precision Medicine heme space, clinical biomarker data from our group from the first-in-human trial for Etentamig (AbbVie’s BCMAxCD3 bispecific antibody) supported robust dose optimization and step up dosing schedules.
On the solid tumor side, I wanted to highlight the recent approval of Elahere in ovarian cancer, as a biomarker-directed Antibody Drug Conjugate (ADC) for Folate receptor alpha (FRα) high ovarian cancer. This approval underscores the importance of precision medicine approaches to guide the development of ADCs for solid tumors. In addition to these, we are developing several other ADCs targeting different biomarkers like c-MET, SEZ6 and CD123.
"One key goal for us in Precision Medicine is to optimize ways to select the right patients for our drugs."
What is exciting to you when you look at recent developments in IO modalities?
Over the past few years, in heme malignancies we’ve seen impressive efficacies with bispecifics/T cell engagers and cell therapies, resulting in very durable, almost cure-like responses. In solid tumors, it has been much more challenging to see lasting responses with these types of therapies, although we have recently seen promising results with bispecific T cell engagers in metastatic small cell lung cancer. In addition, new approaches such as engaging co stimulatory pathways through multi-specific molecules, with the goal to overcome immune suppressive mechanisms, has come up in the recent times. These approaches may hold promise in solid tumors.
What is it about T cell engagers that you find scientifically interesting?
T cell engagers, due to their mechanism of action, recruit immune cells to tumors, to enable tumor cell killing. Key determinants of response to T cell engagers include tumor cell expression of the target antigen as well as the tumor microenvironment (TME) and immune fitness in general. Thus to study T cell engagers in the clinic, we need to deploy robust assessments of both tumor cells and immune cells (in blood and TME) to understand response and resistance to these molecules. Comprehensive immune profiling at baseline and on-treatment will help us inform dosing strategies as well as combinations to bypass resistance and maximize patient benefit.
What makes IO and ADCs a potentially potent combination?
One significant recent development for ADC IO combinations was the recent approval of this approach in patients with locally advanced or metastatic urothelial cancer. The combination treatment almost doubled overall survival, compared to platinum-based chemotherapy.
Mechanistically, there is a rationale for combining ADC and IO therapies, based on a number of mechanisms through which ADCs induce immune responses either directly (ie. antibody effector function or payload effects on immune cells) or indirectly (via killing of tumor cells). Preclinical data have shown that ADCs are able to increase T cell infiltration into tumors and thus it makes a lot of sense to combine with agents such as checkpoint blockade that reinvigorate T cells. The goal of ADC-IO combinations would be to extend ADC treatment responses, make them more durable, ultimately improving outcomes for patients. Not surprisingly, there are many ongoing clinical trials investigating the combination of antibody-drug conjugates and immunotherapy and I look forward to emerging data from these trials.
What would be the next steps in further investigating IO-ADC combinations?
We need to continue to investigate ADC and IO therapies in the clinic and learn from current trials to be able to optimize these combinations. Precision medicine strategies that characterize both tumor and immune compartments will be key to guide these therapies to patients most likely to respond, as well as guide dosing regimens.
It will also be important to understand mechanisms of toxicity when you combine ADCs and IO therapies. There is potential overlap in toxicities between ADCs and some of the IO agents, and as a field, we need to learn how you combine these therapies and balance toxicity and efficacy in the clinic.
"Precision medicine strategies that characterize both tumor and immune compartments will be key to guide these therapies to patients most likely to respond, as well as guide dosing regimens."
What do you find fulfilling about medicine development?
In my over two decades of drug development experience in the industry, my passion and commitment has been the chance to positively impact lives of patients. I have worked in both Discovery Research and Translational Research/Clinical biomarkers, which introduced me to the world of precision medicine. I quickly realized that precision medicine is what I was really excited to pursue further.
In this space, we are tasked with understanding why drugs work in some patients and may not be as effective in others, a knowledge that can help guide the development medicines with higher potential of success. At AbbVie as the head of Oncology Precision Medicine, I am fortunate to pursue this passion with an incredibly dedicated team. I look forward to working with this team as we strive to bring novel medicines to patients faster.
What advice or lesson learned has helped shape your career path?
On a day-to-day challenges side, the biggest lesson I learned was to get energy from failure or obstacles. When things get tough (which they always do), use that as a way to pursue it even harder. There are always things that go wrong in science. Having the right mentality to push ahead is very important.
On the career progression side, think about where you want to be and what you want to do next. Even if you love what you are doing right now, there are opportunities that either help you grow in your current job and/or paths outside of that you might never be exposed to unless you explore (via shadowing for example). Therefore, it’s important to take the time to know where you want to be and be very deliberate about your career journey.
What advice would you give young people, especially young women, entering science careers?
My advice for young women entering into science careers would be to believe in themselves and have confidence in their abilities. They should embrace their potential, aim high and go for it! I would also encourage them to find their “village” and build a supportive network of mentors, peers, and allies and then use that at every step of the way- for guidance, encouragement, advice or exploring new opportunities.
What is one lesson you’ve taken from a career in medicine development?
Drug development is not an individual effort, it is a complex and challenging process and it requires the collaboration of multiple disciplines and areas of expertise. Thus, one key lesson I've learned is the importance of working well within and across teams. This involves the ability to build bridges, to work well cross functionally, to listen well and to bring others along.
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