Biotech Strategy Blog

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

Posts tagged ‘GDC-0032’

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.

Genentech’s next generation PI3-kinase inhibitor, GDC-0032, was the topic of two presentations yesterday at the 2013 annual meeting of the American Association for Cancer Research (AACR) taking place in Washington D.C.

Genentech have put substantial resources into developing new agents that target different elements of the PI3K pathway.  These include: GDC-0941, GDC-0980, GDC-0084, GDC-0349, GDC-0068.  At this year’s AACR, data on their latest compound, GDC-0032, was presented. This agent is a selective inhibitor of PI3K alpha, delta and gamma but spares inhibition of the PI3K-beta isoform.

In the New Drugs on the Horizon session, Alan Olivero from Genentech gave a fascinating talk (if you are a medicinal chemist) on how the chemical structure of GDC-0032 was rationally developed. He described how a slight change in structure can lead to a very different selectivity profile.

One way in which GDC-0032 is novel, is that it spares the beta-isoform of PI3K, which Genentech hypothesize may reduce some of the undesired side effects such as effects on metabolism, previously seen with pan PI3K inhibitors such as GDC-0941.

Olivero noted that GDC-0032 has greater maximal efficacy and more potency than GDC-0941 in PI3K alpha mutant xenograft tumors as compared to wild-type ones.

The results of a first-in-human phase 1a dose escalation study for GDC-0032 were presented at AACR 2013 in yesterday’s Clinical Trial Symposium (Abstract LB-64).

Dejan Juric MD (Massachusetts General Hospital) presented promising early clinical data for GDC-0032 in PI3KCA mutant cancers, especially breast cancer.

The results showed that in PI3KCA mutant breast cancer there were 4 cPR (RECIST -30 to -70%) and 2 SD out of 6 patients, all of whom had measurable disease with pre-treatment.  

One confirmed partial response in PI3KCA mutant breast cancer took place after 11 lines of prior therapy in a 74 year old woman with HER2- breast cancer, who subsequently became triple negative.  Another patient with a confirmed partial response had HER2+ ER+ metastatic breast cancer.

While this early data is promising, further clinical trials are needed to validate it.  Dr Juric concluded his presentation by noting that,

“GDC-0032 is being further explored as a single-agent in solid tumors and in combination with endocrine therapies in breast cancer including letrozole and fulvestrant.”

If you are interested in GDC-0032, then other presentations at AACR this week to watch out for are:

Abstract 2382 (Tuesday Apr 9, 8-12 am Poster Section 2, Board 2) Development of predictive biomarker gene expression signatures that associates with drug sensitivity and kinase activation in breast cancer.

Abstract 4470 (Tuesday Apr 9, 1-5 pm Poster Section 41, Board 28) Mechanisms of acquired resistance to the PI3K inhibitors in colorectal cancer cell lines.

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