Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘AP26113’

With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:

“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”

Good question.

There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.

Reading Market Philly Chocolate TowerTo maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.

When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!

I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research.  Thank you for joining our conference coverage service, we really appreciate it.

To learn more about the hot topics in targeted therapies for cancer research, you can log in or sign up in the box below.  Read on…

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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.

Last week saw the release of the majority of the abstracts for the 2013 European Cancer Congress that takes place at the RAI conference center in Amsterdam from September 27 to October 1st (Twitter hashtag #ECC2013). Not yet available are the late-breakers and those abstracts included in the media press conference program.

ECCO Congress BannerThe European Cancer Congress is the euro equivalent of the American Society of Clinical Oncology (ASCO) annual meeting and is organized in alternate years by the European CanCer Organization (ECCO) and European Society for Medical Oncology (ESMO). This year it’s the turn of ECCO who ran an excellent meeting in Stockholm in 2011.

Scan the QR code to download the ECCO Amsterdam Cancer Congress AppHere are links to the #ECC2013 abstracts and searchable Congress programme.

There is also an ECCO App that’s well worth downloading. It offers the meeting program with links to abstracts, as well as floor plans and can also be used to follow the #ECC2013 conversation on Twitter.

ECCO have made it as easy as possible for people to download the app, just scan the QR code and it will take you to the download page for your phone (iPhone or Android).

ECCO have also published their list of abstracts not to be missed – a few on their list that stand out for me include:

Breast Cancer:

1859 – PI3KCA mutations and correlation with pCR in the NeoALTTO trial (BIG 01-06)

Prostate Cancer:

2853: An open-label phase 1/II safety, pharmacokinetic, and proof-of-concept study of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (CRPC).

2854: The effects of enzalutamide (ENZA) in combination with abiraterone acetate (AA) in patients with bone metastatic castration resistant prostate cancer (mCRPC)

Lung Cancer:

3401:  Updated results of a first-in-human dose finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies.

3408: Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1)

Ovarian Cancer:

In the plenary Presidential sessions several of the presentations focus on ovarian cancer with results being report for the following trials: ICON6 (cediranib), AURELIA (bevacizumab), ICON7 (bevacizumab).

As always I will be mining the posters for gems, and attending as many of the scientific and educational sessions as I can.

Regretably, to offset costs, I will be introducing a paywall for most of the conference coverage from ECC2013 in Amsterdam. In this respect I’m following leading publications such as The New York Times and The Wall Street Journal. I will be providing some additional commentary to those who subscribe to BSB email alerts so do sign up if you have not already done so.

I hope to see you in Amsterdam!

Update Sept 17: Preview of Late Breaking Abstracts and PI3K Abstracts

Sally Church (@MaverickNY) has published her ECCO 2013 preview on Pharma Strategy Blog (free access). Abstracts that caught Sally’s attention included those on T-DM1, everolimus, FLT1 gene varation in NSCLC and evaluation of GDC-0032, a next generation PI3K inhibitor.

Data on GDC-0032 and its early promise in breast cancer was presented at the AACR annual meeting earlier this year.

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.

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