By Ray Tobey, Chief Medical Officer on Sep 27, 2017 9:00:00 AM
There’s never been a more optimistic time in the history of cancer clinical trials than the present, thanks to immunooncology. Through only a couple of many potential therapeutic modalities, immunooncology’s impact in clinical trials has palpably changed the research and clinical landscape.
Outside of the trial scene, immunooncology is becoming a household term after saving lives at a volume that was unattainable by the standard of care of yesteryear.
Immunooncology isn’t one undifferentiated bloc of trials or one single set of drug targets, though. If anything, immunotherapy is as versatile as it is clinically impressive.
Many Principles, Many Pipelines
Clinical trials for immunotherapies are humming along, but so far most immunotherapies for oncology are targeted antibodies against a small handful of popular ligands rather than more outlandish methods. It’s understandable why researchers would prefer to continue to generate therapies which can save lives rather than branch out in search of new immunotherapy targets.
That hasn’t stopped some intrepid research groups from trying, though. Speculative methods like adoptive cell transfer for personalized immunooncology haven’t panned out in trials yet, so there’s nothing wrong with going with what works.
Drug developers have taken to the antibody based immunotherapy model with great gusto, using antibodies targeting the same ligands in varying disease contexts and combinations to maximize the number of trials started.
In Astra-Zeneca’s immunooncology drug trial pipeline in particular, the breadth of immunotherapy’s potential is evident, as is their reliance on antibody based immunotherapies. Despite the massive pipeline of trials currently in action, the monoculture of antibody based therapies targeting a mere few critical ligands shows no sign of growing stale.
It’s clear that there are a few specific cancers that are on the chopping block for antibody based immunotherapies:
- Aggressive Pancreatic Cancer (Ductal Carcinoma)
- Bladder Cancer
- Head and Neck Squamous Cell Carcinoma
- Non-Small Cell Lung Cancer
What’s On The Frontier Of Immunooncology?
Expect to see combination therapies, multispecific immunotherapies, novel therapies, and adoptive cell therapies hitting the trial scene imminently. The exact targets of these therapies will likely be branching out from the pre-established core that’s currently dominant in the trial scene, especially if they use a more outlandish delivery mechanism like adoptive cell therapy to target multiple oncoprotiens. There’s also a good chance that these new therapies will be paired with other, more established therapies.
Combination therapies might include traditional anti-cancer measures like radiation or chemotherapy in addition to immunotherapy and would provide a multi-modal pair of punches against resistant cancers, provided that the traditional treatment doesn’t interfere with the immunotherapy. Cancer pathologies that were previously untouchable, like solid tumors and advanced malignancies, now have potential treatments thanks to immunooncology.
Novel immunotherapies could use tried and clinically tested elements like antibodies to rouse the body’s cells to fight cancer, rather than targeting cancer directly. In contrast, multispecific immunotherapies could be especially compelling in the clinic because of their ability to accomplish more than one goal at once.
The next batch of Phase I trials will show which route researchers and clinicians think have the best chance of success.
-  https://www.wsj.com/articles/cancers-super-survivors-how-immunotherapy-is-transforming-oncology-1417714379
-  http://www.sciencedirect.com/science/article/pii/S147149141400183X
-  http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2013.10.015/full
-  http://science.sciencemag.org/content/348/6230/62
-  https://www.azimmuno-oncology.com/clinical-trials.html
-  https://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/UCM447165.pdf
-  http://pathology.med.upenn.edu/news/fdas-breakthrough-therapy-designation-leukemia-immunotherapy
-  http://www.onclive.com/web-exclusives/immunotherapy-combination-receives-breakthrough-designation-for-pancreatic-cancer
-  http://cancer.unm.edu/2015/02/26/fda-grants-breakthrough-therapy-designation-for-mpdl3280a-an-anti-pdl1-investigational-cancer-immunotherapy-for-non-small-cell-lung-cancer/
-  https://www.cancercommons.org/news/fda-grants-breakthrough-designation-to-personalized-immunotherapy-for-all/
-  http://www.sciencedirect.com/science/article/pii/S1074761313002860
-  https://www.bluebirdbio.com/our-focus/cancer-immunotherapy/
-  http://cancerimmunolres.aacrjournals.org/content/2/9/831.short
-  http://www.sciencedirect.com/science/article/pii/S030438351630074X
-  http://cancerres.aacrjournals.org/content/75/15_Supplement/4297.short