Today, we face a significant public health challenge where countless potentially life-saving oncology drugs are sitting on the sidelines unused because they failed to demonstrate clinical efficacy in phase II trials. These unused drugs include treatments that could give hope to patients and families affected by cancers currently deemed incurable (e.g., platinum-resistant ovarian cancer) and also improve outcomes for difficult-to-treat cancers (e.g., head and neck squamous cell carcinoma).
What’s perplexing is that these drugs do produce positive outcomes in a subset of patients during clinical trials, but it is often unclear exactly which patients they’re most effective in. This lack of stratification or ability to identify likely responders ultimately results in failure to pass clinical trial criteria and gain FDA approval and widespread use.
How can we help progress these promising therapies to the clinic? Companion diagnostic (CDx) tests are emerging as a critical success factor.
CDx tests are tied to a specific drug. They are intended to help predict treatment response and match that drug with the right patients (likely responders), thereby increasing positive patient outcomes. While a drug by itself might not receive FDA approval, a drug combined with the appropriate CDx might clear that threshold. A success story is that of olaparib (Lynparza), a DNA repair inhibitor, and BRACAnalysis CDx, a test that probes for BRCA gene mutations and identifies patients most likely to respond positively to olaparib. These were approved in December 2014 for use together in the treatment of breast cancer.
Advances in genetics have garnered much attention from scientists and propelled the field of precision oncology forward. Genetics-based approaches work best for cancers with a single genetic driver. Unfortunately that comprises only about 10% of cancers. So, what can we do about the 90% of cancers with more complex molecular determinants?
One company, Acrivon Therapeutics, believes the answer lies in proteomics.
“As I see it, pharma and biotech will continue to move towards proteomics-based methods to identify responders … with only [genetic] information, you must infer and hypothesize which protein signaling pathways are driving the disease and also how the drug acts on these. With protein-based methods, you can basically measure the activity states of the pathways that are driving the disease, and you can directly measure and observe how the drug acts on these pathways.” – Peter Blume-Jensen, MD, PhD, founder, president, and CEO of Acrivon Therapeutics
Acrivon is a clinical stage biopharmaceutical company developing precision oncology medicines that it matches to patients whose tumors are predicted to be sensitive to that specific drug. In June 2022, Akoya Biosciences and Acrivon announced a partnership wherein Acrivon will leverage Akoya’s multiplex immunofluorescence and spatial phenotyping technologies in its OncoSignature companion diagnostic tests. This partnership enables fast, high-resolution tissue profiling for clinical trial selection.
“I’ve known members of the Akoya team for many years, and we consider them to be the leading provider of the spatial biology technology needed to further develop and validate our OncoSignature test into a companion diagnostic test. Together, we’re pioneering an approach that hasn’t been used before.” – Peter Blume-Jensen, MD, PhD, founder, president, and CEO of Acrivon Therapeutics
So far, this proteomics-based biomarker strategy appears to be on the right track. In May 2023, Acrivon announced that positive phase II trials of its investigational drug ACR-368 have resulted in two FDA fast-track designations for treating ovarian and endometrial cancer. Shortly thereafter, in November 2023, the FDA granted breakthrough designation to the ACR-368 OncoSignature assay for ovarian cancer.
Peter Blume-Jensen, MD, PhD, founder, president, and CEO of Acrivon Therapeutics and Brian McKelligon, CEO of Akoya Biosciences, recently sat down with the editor in chief of Inside Precision Medicine to discuss this unique approach and their vision for the future of precision medicine. You can check out the full article and Q&A here.
Other resources:
- Partner with our Advanced Biopharma Solutions (ABS) team and get expert help developing your assay
- Learn more about clinical applications of spatial proteomics
