Here’s my 2010 list of a few pipeline and approved products that I’ll be watching out for at the upcoming American Society of Hematology (ASH) meeting , which begins tomorrow and runs over the weekend.   Some of them will not the expected hot ‘news’ items so beloved of the medical media who often seem to delight in over-hyping things.

Saturday and Sunday typically embrace the posters, education and plenary sessions, while Monday and Tuesday heralds the oral sessions.

In no particular order, and by no means extensive, these are agents I personally find interesting and worth checking out at the meeting:

1. ARRY-520 (Array Biopharma)

There is still no cure for multiple myeloma, although a wealth of new therapies and combinations has definitely improved survival and outcomes for this disease.  It is always good to look out for new agents in development in the relapsed/refractory setting.

ARRY-520 is interesting because it’s a kinesin spindle protein (KSP) inhibitor.   KSP is required for cell cycle progression through mitosis and inhibition of KSP has been shown to induce mitotic arrest and cell death, in a similar fashion to taxanes and vinca alkaloids. The company has a number of small molecule compounds in development for cancer:

Picture 1 Whats Hot at ASH in 2010?Source: Array Biopharma

ARRY-520 has been researched specifically in hematologic models such as myeloma, so this will a poster I’ll be looking out for.

What I love about this compound:
While ARRY-520 may target the spindle like taxanes, it appears to do so without the associated peripheral neuropathy and hair loss.

2. SGN-35/brentuximab vedotin (Seattle Genetics/Millennium):

I wrote about the recent promising data from the NEJM by Dr Anas Younes and colleagues. At ASH the same group are presenting on SGN-35 in relapsed/refractory Hodgkin Lymphoma including adverse events and ORR (Mon 6th, 7am) and another group is looking at the agent in Anaplastic Large Cell Lymphomas (Tues 7th, 7.30am) where they will be presenting data on complete remissions.

What I love about this compound:
The concept of a monoclonal antibody combined with chemotherapy as a drug conjugate is an exciting new disruptive biotechnology with a lot of promise.

3. CAL-101 (Calistoga)

Most (but not all) of the other PI3-kinase inhibitors in development seem to have been focusing primarily on solid tumours with mixed results to date.  There is also a potential role for the delta form of PI3 kinase inhibitors in B-cell signalling, which encompasses Non Hodgkins Lymphoma (NHL), Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL).   Calistoga have been looking at CAL-101 specifically in hematologic malignancies and 7 abstracts are being presented this year either alone or in combination.

What I love about this compound:
When everybody zigs, zag.

4. Crizotinib (Pfizer)

This year, we’ve all heard a lot about ALK rearrangements in non-small cell lung cancer (NSCLC), but such translocations also occur in anaplastic large cell lymphoma (ALCL).  It would be most logical to see if crizotinib has any effect in these people with this uncommon form of lymphoma, so I’m looking forward to seeing what the data looks like in the poster session on Sunday evening.  I’m expecting/hoping it will show some positive signs in this particular subset who are chemorefractory.

What I love about this agent:
It’s highly and specifically targeted to ALK, a constitutively active translocation (and occasional mutation) that appears to be driving some lung cancer, lymphoma and other rarer cancer subsets.

5. Imatinib/nilotinib (Novartis)

How low should you go?  It is now clear from the evidence that people living with CML who attain a major molecular response (MMR) are less likely to relapse than those with a complete cytogenetic response (CCyR).

Ten years ago, the expected life span was only 3-4 years.  Imatinib has dramatically shifted the paradigm for the treatment of CML, with people having a realistic goal of living for at least a decade after diagnosis with early chronic phase disease.  It is likely that the baton will soon pass to the new second generation TKIs such as nilotinib and dasatinib, which can help achieve an earlier response into the ‘safe haven’ zone.  They typically all achieve 90% response rates, but differ in their side effect profiles owing to the additional targets they inhibit.

It will be interesting to see what new data will be presented at this meeting in the annual IRIS trial update and other presentations in several sessions on Monday 6th.

What I love about this drug:
You can’t keep an old warhorse down!

6. Ponatinib (Ariad):

None of the TKIs currently approved for CML target the rare T315I mutation, which ponatinib does target, based on preclinical data.  Initial phase I data in the relapsed/refractory setting including T315I mutations is due to be presented in Orlando in the oral session (Monday 6th, 8:15am).

What I love about this compound:
Resistance to all of the TKIs is not that common in CML, but I do think it would be good to have an option for those who find themselves in that unfortunate situation.

7. Rituximab (Roche/Genentech):

Most of the plenary presentations on Sunday afternoon are scientifically focused this year, but there is some preliminary clinical data on rituximab in follicular lymphoma (FL).

The randomised trial from the UK looks at rituximab versus a watch and wait strategy in patients with stage II, III, IV, asymptomatic, non-bulky FL.  The reason for this is that patients with asymptomatic, advanced stage, follicular lymphoma have shown no benefit of immediate chemotherapy when compared with a watchful-waiting approach, so chemotherapy is typically deferred until disease progression.  Rituximab (when used with the CHOP chemotherapy regimen) has become the standard of care for NHL, so looking at it’s activity in another lymphoma subset makes sense.

What I love about this compound:
Anything that significantly delays disease progression without the side effects of chemotherapy would be a welcome addition to treatment options in FL.

8. Concomitant VEGF and MEK inhibition

There are a couple of novel approaches looking at new combinations at the ASH meeting. Thoughtful research studies can often inform us about a potential new approach that might be worthwhile considering in the clinic.  One such example I came across was dual VEGF and MEK inhibition in pediatric 11q23 AML.  In AML, it has been found that simultaneous activation of these pathways results in a poor prognosis, so this would be a logical therapeutic combination to consider in appropriate children.  Chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene at locus 11q23 are also associated with a poor outcome.  These translocations represent approx. 15-20% of pediatric AML.

What I love about this concept:
As a result of the preclinical research, future studies looking at a VEGF-MEK combination are now being planned in pediatric AML and will be worth watching out for.

9. Panobinostat and everolimus (Novartis)

Believe it or not, I was actually trying very hard to avoid selecting another Novartis drug or combination, but they have a very broad portfolio in oncology and lots of interesting early data coming out. The reasoning behind this combination is that mTOR and deacetylase (DAC) inhibitors have demonstrated single agent activity in patients with relapsed and refractory lymphoma. Synergy between DAC inhibitors and mTOR inhibitors has also been observed in lymphoma cell lines in vitro. This is a phase I dose finding trial, so the results will be preliminary, but we should see whether the promise is possible from the early signals.

What I love about this concept:
HDAC and mTOR is a highly logical combination to explore in lymphomas based on the preclinical research to date.

10. TET2 mutations in myeloid malignancies

In case you’re thinking this might be a bit obscure, this presentation actually kicks off the Plenary session on Sunday and I have to say that it’s cool to see a Masters student present some really cool research.

“TET2 mutations are frequently found across broad spectrum of myeloid malignancies but how these mutations contribute to diseases is still unknown.”

I’m not going to spoil the presentation, but what I suspect they may have is a new therapeutic target in myeloid malignancies based on a mutation that occurs through epigenetic changes.

To check out some other top lists, take a look at Dr Anas Younes Facebook page, where he has posted his top 10 lymphoma clinical abstracts.  I haven’t seen any other 10 ten abstracts for ASH yet, so we may well be the first two to stick our necks over the parapet icon smile Whats Hot at ASH in 2010?

Disclosures:

– I own no stock in any of these companies (perhaps I should!)
– I’m a former employee of Novartis who worked on imatinib and my company has done consulting work for them.