2012 ESMO Abstracts

Here is a link to 3 ESMO abstracts for second generation ALK inhibitors and one HSP90 inhibitor.


In short
AUY922 – 29% partial response (21 patients)
AP26113 – 100% partial response in patients resistant to Crizotinib (4 patients)
LDK378 – 81% responses of patients resistant to Crizotinib (26 patients)
CH5424802 – 73% partial or complete responses (15 patients, all Crizotinib naive)

This is a brief analysis from Rachel McMinn today at Merrill Lynch:

Initial ARIA ALK data encouraging ALK inhibitor data for ARIA, Chugai, Novartis

Abstracts became available today for the European Society for Medical Oncology (ESMO) meeting which will take place in Austria, Sept 28 – Oct 2. New data show positive preliminary results for ARIA’s ALK inhibitor ‘113, and suggest ARIA is well positioned in a highly competitive and evolving lung cancer drug development landscape. Competitor data from Novartis is unchanged from data previously presented which showed promising activity in Xalkori failures with GI tox as dose limiting; Chugai’s ‘802 shows also shows strong initial activity with neutropenia as dose limiting. Updated ‘113 results will be presented at the meeting.

ARIA’s ‘113 shows activity in ALK+ lung, no data in EGFR
Phase 1 study of ‘113 evaluated four dose levels (30mg, 60mg, 90mg, 120mg; 1x/day) in 11 non-small cell lung cancer and 4 other cancer patients (10 patients ALK+ or EGFR-mutated). No treatment related serious adverse events (AEs) were observed and no dose limiting toxicities occurred. Most common AEs were fatigue (n=4) and nausea (n=4). We note that gastrointestinal tox is expected and potentially mechanism driven. The drug demonstrated a clear anti-tumor activity
with partial responses recorded in all ALK+ patients tested (60mg n=1 and 90mg n=3). 120mg dose is currently under evaluation and data are expected at the meeting.

Chugai’s ‘802 data solid Data from a Phase 2 study of ‘802 (300mg, 2x/day) in ALK+ NSCLC showed a 73% response rate (1CR and 10PRs) in 15 evaluable patients, who are naïve to
an ALK inhibitor. The data are solid but tell us nothing about potential efficacy in Xalkori failures. Most common AEs included liver enzyme elevations, neutropenia, rash, nausea, myalgia, dysgeusia, constipation, blood CPK/bilirubin/ALP elevations, all Grade 1 except for neutropenia (Grade 3).

This entry was posted in alectinib - Alecensa from Chugai - Roche - GenenTech, brigatinib-Alunbrig from Takeda, ceritinib - Zykadia from Novartis, Lung cancer, Potential Treatments, Research, Side Effects. Bookmark the permalink.

2 Responses to 2012 ESMO Abstracts

  1. admin says:

    I found several interviews that were done at ESMO.

    In particular, here is an interview with Dr. Shaw discussing the first Phase 3 trial of Crizotinib. In addition to confirming a PFS benefit for those who take Crizotinib over chemo.

    It also confirms that there is a improvement in PFS for those who take Pemextred (Alimta) as compared with Docetaxel. Also, the objective response rates were quite different for the two chemotherapy arms – 6.9% for docetaxel and 29% for pemetrexed.

    http://www.onclive.com/conference-coverage/esmo-2012/Positive-Results-in-AL K-Positive-NSCLC-With-First-ALK-Inhibitor

    Look under the related videos and articles in the lower right hand area to find several other interviews.

  2. admin says:

    At ESMO, Ariad updated their data. The new data shows that 8 (73%) of 11 ALK patients had a partial response to AP26113. The longest response to date has been 9 months.

    One patient also had brain Metastasis, that patient had a partial response in those metastasizes.

    An objective response occurred in one patient at 60mg. Dosage is currently being tested at 240mg (with a max plasma level of 3373 nM and a trough plasma level of 1243 nM, the half life is 21 hours). The MTD has not yet been reached.

    Here is a link to the presentation http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9MTU1MjE5fENoaWxkSUQ9LTF8VHlwZT0z&t=1

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