Boston – Preclinical data for PF-06463922 (Pfizer), a next generation ALK inhibitor, with potency for all known Crizotinib ALK resistant mutants and ability to cross the blood brain barrier was presented today at the 2013 International Conference on Molecular Targets and Cancer Therapeutics co-hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI) and the European Organization for Research and Treatment of Cancer (EORTC).
In addition to being a competitor to other next-generation ALK inhibitors in development such as AP26113 (Ariad), LDK378 (Novartis) and alectinib (Roche/Chugai), PF-06463922 shows activity in both crizotinib-naive and crizotinib-resistant cells, so could end up being a replacement for crizotinib (Xalkori) front-line if clinical results confirm preclinical efficacy.
There’s a lot going on in lung cancer right now, which is pretty amazing when you consider only a couple of years ago we were still talking only chemotherapies and EGFR inhibitors.
Much of the new attention has been on the EML4-ALK translocation, the T790M mutation responsible for EGFR resistance as well as the possibility of improved survival with either MET or MEK inhibition. There are others, but these are the main ones that jump to mind.
Today, I want to focus on ALK+ lung cancer and what’s in store at ECCO at the weekend.
In her annual preview video of what’s hot at ASCO 2013, Sally Church (@Maverickny) discusses several therapeutic areas with new data at the meeting including:
- Immunotherapy (PD-1, PD-L1, CTLA-4)
- CLL (GA-101, idelalisib, IPI-145)
- Breast Cancer (palbociclib, PF-05280014)
- Lung Cancer (LDK-378, AP26113)
- Pancreatic Cancer (Abraxane, TH-302)
This video was originally published on Pharma Strategy Blog and includes an edited mechanism of action (MOA) for PD-L1 (courtesy of Roche/Genentech). Several people have since remarked it’s the first time they fully understood what “upregulation” meant.
If you missed the video, it’s well worth watching again in the run up to ASCO 2014.