Following on from yesterday’s post about learnings from the Boston AACR-NCI-EORTC conference in immuno-oncology, today’s post focuses on learnings from non-immune R&D, namely monoclonal antibodies and TKIs.
We know that cancer is a very complex topic and that adaptive resistance is increasingly a huge focus, but where are the new developments in this area and what can we learn from them in order to improve outcomes?
Another key area to consider is therapeutic index, that is are we shutting down enough of an oncogenic target’s activity in order to ensure efficacy? We’ve seen this in the anti-angiogenesis field, for example, where many VEGF inhibitors failed before bevacizumab (Avastin) finally cracked the nut in colorectal cancer and shifted the needle in terms of improving overall survival. We are now seeing this happen in other areas too, which will be covered below.
Immuno-oncology is fast becoming one of the hottest topics in cancer research following the approval of the anti-CTLA4 checkpoint antibody, ipilimumab, in advanced melanoma, as well as emerging solid data from anti-PD-1 and PD-L1 antibodies in melanoma, lung and renal cancer at ASCO in June.
The big question on many people’s minds though, is what other checkpoint inhibitors are out there and can they safely be used either as single agents or in combination with the above agents, or even with existing standard of care combinations (chemotherapy and targeted therapies)?
I have long argued that what will really make a difference in this space is combinations and the ability of sponsors to successfully evaluate novel-novel agents in clinical trials. After all, BMS have a huge advantage with ipilimumab and the ability to combine it with their PD-1 or other immunotherapeutics, since their rivals will be greatly hampered by the $120K per person price tag for the commercial drug required as part of clinical trial costs.
This means most companies in this space are looking at other options in the search for better outcomes.
At the AACR-NCI-EORTC Molecular Targets conference in Boston this week, the last day was devoted to two sessions in immune-oncology and one of the plenary sessions included Dr Susan Topalian discussing an update on nivolumab and anti-PD-1/L1 therapies post ASCO. There was also ample opportunity to discuss immunotherapy with the many attendees in the busy poster sessions.
The first immunotherapy session on Weds morning particularly caught my attention and it seems a good opportunity to summarize some of the key observations emerging in this field. Here are my detailed notes from the session, which raise a lot of fascinating questions from the presenters about this field and – more importantly – where it’s going: