Acute Myeloid Leukemia (AML) is usually a disease of the elderly and an area of high unmet medical need, especially in those who unfortunately relapse post stem cell transplantation (SCT) or are considered ineligible for a transplant. In some ways, it has languished in the graveyard of R&D with very few new therapies approved by the FDA or EMA over the last decade. In fact, it has been quite the opposite with Pfizer’s gemtuzumab ozogamicin (Mylotarg), an anti-CD33 antibody drug conjugate (ADC) approved and subsequently withdrawn from the US marketplace following lack of confirmatory phase III data.
The list of agents, targeted and and cytotoxics, that have been evaluated and found wanting in the elderly AML setting is very long. These patients are usually considered ineligible for transplant and rather challenging to treat given the concomittant co-morbidities and often frail performance status often exclude them from drug clinical trials also. A number of phase II trials have also generated promising efficacy data, only to fall short in larger randomised studies.
There are now a new raft of compounds in development, quite a few with data at ASCO or EHA, making it a suitable time for an update of the AML landscape.
Companies mentioned: Karyopharm, Astellas, Ambit, Arog, Sunesis, Celgene, Novartis, Genentech, Agios
Compounds mentioned: selinexor, ASP2215, crenolanib, quizartinib, trebananib, vosaroxin, Vidaza, midostaurin, ABT-199, GDC-0199, AG–221, TIM3.
To read more about our insights and review of the AML data at ASCO, you can sign in or sign up in the box below.
To round off our series of post AACR reviews this week (there will be more coming next week as well, don’t worry), I wanted to look at some interesting non-immunotherapeutic agents that I found compelling and worth watching out for in the future.
A couple of things to remember or understand is that AACR is a very different conference from ASH and ASCO, aside from the presence of noticeably more science:
a) Much of the data presented at this meeting is either preclinical or phase I-II cinical data
b) Most of these studies are usually exploratory or preliminary in nature
Phase I trials are usually designed to evaluate dose finding in either a single agent or with an untested and untried combination. Investigators are interested in a number of key things here, which might include:
- Maximum tolerated dose (MTD)
- Dose limiting toxicities (DLT)
- A recomemmended phase II dose (RP2D)
- PK and PD
- General tolerability assessment.
Sometimes a different formulation is tested, in which case bioavailabity is also important. To be expressly clear though – any efficacy signals seen are a bonus. That’s the main purpose of phase II trials.
That said, one of the things I most like about AACR is the early phase I data in new targets or data that explains why resistance develops as an adaptive response to therapy. With these in mind, here are three excellent examples from well put together research from the meeting that we can learn a lot from.
To read more about our analysis of up and coming compounds including:
DEDN6526A, a novel ADC in melanoma; AG–221 in IDH2 mutant AML and MDS; a PI3K-α isomer-specific inhitor, BYL719, and the impact of PTEN alterations
You can sign in or sign up below to learn about our insights and analysis of these studies.