This past week, a record-breaking 2,700+ people attended the 31st annual meeting of the Society for Immunotherapy of Cancer (SITC) in National Harbor, Maryland. SITC is a world-leading, member-driven organization that brings stakeholders together from industry, academia, research, clinical care, policy, and government to explore the growing promise of immunotherapy, particularly it’s potential to treat patients with certain cancers.
Here at NanoString, we believe we are doing our part to usher in this new era of personalized medicine. We are working closely with researchers, clinicians, and governing bodies to develop and commercialize new immunotherapy-based products that will help deliver safe and effective health care.
Although we believe that cancer immunotherapy is here to stay, broad adoption of immunotherapy will not come without its challenges. Come along with us on this journey to explore the opportunities and challenges for cancer immunotherapy. Through our newly launched nForm blog, we’ll comment on critical events and advances that we believe are important to understanding this fast evolving field.
To start, let’s take a deeper look at the 2016 SITC meeting.
SITC hosted a number of new sessions this year to accommodate the diversity of attending professionals and stakeholders interested in immunotherapy research and treatment. Providing a comprehensive overview of the development in the field in a relatively condensed format, this year’s conference included a half-day program, complete with presentations from members of industry, patient advocacy groups, payers, academics, and pharmacy about the value of cancer immunotherapy and how to accurately assess it. This is an important emerging issue; while value models exist to better understand the financial implications of therapy choices in cancer, these models so far have been based largely on chemotherapy regimens. However, immunotherapy drugs are different in terms of their effectiveness due to the durability of benefit associated with them, although often limited to a subset of patients due to cost and side effects profile.
The cumulative effect of the presentations and discussions left us with some significant themes:
- Anti-PD-1/PD-L1 drugs have and continue to gain Food and Drug Administration approvals in an increasing number of advanced solid tumors. These decisions have been based on significant long-term clinical activity in a subset of those patients, thus confirming the broad validity of this approach in the clinic. There are now three approved drugs targeting this important checkpoint pathway: nivolumab and pembroluzimab (anti-PD-1 monoclonal antibodies), and atezolumab (anti-PD-L1 monoclonal antibody), which have been approved in many indications such as advanced melanoma, NSCLC, urothelial cancers, head and neck cancers, Hodgkin disease and renal cancers. More approvals are expected based on regulatory submissions currently under evaluation and positive signals of clinical activity in multiple additional cancers including colorectal, small cell lung, gastric, etc.
- The dramatic success of these drugs has spurred an exponential increase in research resulting in a new wave of immuno-oncology candidate drugs that are now being tested clinically. Although it is possible that some new agents will come along and prove themselves as powerful single agent drugs, it seems more likely, at least in the foreseeable future, that the key of maximizing the benefit from new immune-oncology therapies will lie in combinations with other (mechanistically complementary) IO agents and/or standard of care treatments. However, the number of possible combination permutations is vast (e.g., currently more of 800 clinical trials on ClinicalTrials.gov are testing IO combinations), so the key moving forward will be to understand how to rationally combine these agents for maximal anti-tumor activity and acceptable toxicity.
- Biomarkers seem to be the unifying principle for the previous points, including value of cancer immunotherapy: Identify predictors and determinants of response to improve precision and personalization and identify combination approaches that improve responses and overcome/circumvent resistance. The clinical relevance of biomarkers in the development of checkpoint inhibitors is further increasing with the applications of anti-PD-1/PD-L1 drugs as monotherapy in earlier line of therapy (where active standard of care exists) as recently exemplified by the NSCLC first line experience with Keytruda® (which won the approval in this indication in a selected patient population of highly PD-L1 positive tumors) and Opdivo (which failed to prove superiority to standard of care in the same clinical setting but in a less stringently selected patient population).
- Although PD-L1 IHC has been approved as a biomarker for patient enrichment/selection for some of those indications, it remains a suboptimal biomarker, biologically (single analyte spatially and temporally dynamic) and technically. Additional approaches are currently being evaluated that allow measurement and characterization of the broader biology involved in tumor-immune system interactions in a multiplexed fashion. Those include measurements of tumor mutational burden, T cell clonality, and gene expression profiling.
- Gene expression profiling in particular is emerging as a powerful tool for both measuring mechanisms of peripheral immune evasion (adaptive immune escape) as well as patient selection for treatment with PD-1/PD-L1 blocking agents. In a workshop sponsored by NanoString, two examples of applications of the nCounter® technology to the immunotherapy field were showcased. Specifically, Dr. Alexander Reuben, PhD, from the MD Anderson Cancer Center, presented translational research data showing how GEP is informative in elucidating mechanisms of primary and secondary resistance using samples from melanoma patients collected longitudinally before and during treatment with checkpoint inhibitors. This data will guide rational new combination regimens.Dr. Jared Lunceford, from Merck (Pharma partner of NanoString in the development of a GEP signature for selection of patients more likely to respond to Keytruda monotherapy) described the development of the gene expression profiling signature currently being assessed as a predictive biomarker in three Merck sponsored studies.
Photo: Khaaliq Thomas Photography