Info on Liquid biopsy

Abstract e20643 is only available online. In this trial, 10,000 solid cancer patients blood were tested by Guardian360 (a method that sequences compete exons (the part of the DNA that encodes for proteins)). Of those patients ALK fusions were detected in 6%. EML4 was the fusion partner in 81% of the patients and 4 other fusion partners made up the rest of the 19%. 24 patients has ALK+ NSCLC. Mutant alleles ranged from 0.06% to 12.5%. They found several Somatic mutations (SNV) of which 10% were known resistance mutations in ALK. They also found other occurring SNV in other genes that are rare or absent in untreated patients suggesting possible novel Crizotinib resistance mechanisms.

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X-396 update and info on liquid biopsy

Abstract 9056 is an update of info previously published on this site.

The study involved 60 patients of whom 30 were ALK+ NSCLC. Of that 30, 19 (60%) had partial responses (PR).

8 patients were Crizotinib naive and of them 7 (88%) had PRs.

12 patients had prior Crizotinib but no other ALK inhibitor, of them 10 (83%) had PRs.

CNS responses have been observed.

As for the liquid biopsy. ALK was detected in the blood plasma of 16 patients, all of whom responded to treatment. Serial sampling and sequencing demonstrated that a decrease in ALK in patients responding and a increase in ALK at the time of progression. These results do not appear to be robust enough to on their own justify routinely doing a liquid biopsy, but rather an area for more in depth research to be done.

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Alectinib Japan trial abstract

Abstract 9008 covers the J-ALEX phase 3 trial comparing Crizotinib (arm A) with Alectinib (arm B) in TKI naive patients. There were 207 patients at 41 centers in Japan randomized between the two arms.

Arm A had a median PFS of 10.2 months.

Arm B median PFS was not reached.

The trial was stopped early because an independent committee recommended the release of data because the superiority of PFS had been demonstrated.

there is another international trial ongoing.

Posted in alectinib - Alecensa from Chugai - Roche - GenenTech, crizotinib - Xalkori from Pfizer, Lung cancer, Research, Resistance to treatment | Leave a comment

Lorlatinib abstract

Abstract 9009 is a phase 1 dose escalation trial (dose levels ranged from 10-200 mg and the Recomended phas 2 dose was 100 mg once daily). There were 54 patients as of November 30, 2015. 41 are ALK positive and 12 are ROS1 positive. 29 patients remain on treatment.

The analysis of results was broken down into 3 sub groups (for simplicity sake I combine confirmed and unconfirmed results).

Group A had intracranial and extracranial mets. And had an Overall Response rate of 50% (6% complete responses and 44% partial response rate).

Group B had intracranial mets (target and non target mets). And had an Overall Response rate of 44% (28% complete responses and 17% partial response rate).

Group C had intracranial mets (target mets only). And had an Overall Response rate of 60% (30% complete responses and 30% partial response rate).

A phase 2 study is expected to enroll 240 patients across 6 cohorts.

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Britatinib abstract

Abstract 9007 covers the Phase 2 trial (ALTA) comparing two dosing schemes. There were 222 patients who had progressed on Crizotinib. Results where as of 12-7-15.

Arm A received 90 mg straight through.  Arm Breceived 90 mg for the first 7 days then received 180 mg from then on.

Arm A had ORR of 46% including 1 confirmed complete response, median PFS was 8.8 months. There were 3% discontinuations and 7% dose reductions.

Arm B had ORR of 54% including 5 confirmed complete responses, median PFS was 11.1 months. There were 6% discontinuations and 18% dose reductions.

While there were 6% (3% > or = grade 3 ) of early onset pulmonary events within the first 7 days after original dosing. However there were no such events during the first 7 days of increasing the dose to 180 mg.

the data will be updated at the oral presentation.

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Some Summaries of ASCO abstracts

So there are actually 128 different abstracts that use the term ALK in either the body or the title of the abstract. I can not look at all of them. If you want to look them over you can go to abstract.asco.org

I will be summarizing the ones that I find that appear to be of general interest.

To access the database containing the abstracts go to http://abstract.asco.org/176/IndexView_176.html

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Upcoming ASCO abstracts

There are 14 abstracts for the upcoming ASCO that have ALK in the title. But only 6 look like they are likely to be broadly applicable to people on this board. I will be posting summaries over the next week or so. They include updates on Brigatinib (2), HSP90 inhibitors combined with Crizotinib, Alectinib, brain metastases and ALK, and Lorlatinib.

Posted in 3922 - lorlatinib by Pfizer, alectinib - Alecensa from Chugai - Roche - GenenTech, AP26113 - brigatinib from Ariad, Brain metastases, crizotinib - Xalkori from Pfizer, Lung cancer | Leave a comment

Entrectinib phase 1-2 trial update

Entrectinib was tested in 119 patients with three kinds of mutations: NTRK+, ALK, and ROS1. Efficacy data was reported for 24 patients.

For ALK there appear to have been 5 patients, and 57% of them had a tumor response (presumably not all partial responses). The article said “‘This response is comparable to Crizotinib,’ Dr Gandhi said ‘With the next generation of ALK inhibitors likely to replace Crizotinib, the bar is set high for targeting ALK,’ she added.'”.

For ROS1 the overall response rate was 86% (12 of 14) (presumably not all partial responses).

For NTRK+ the overall response rate was 100% (5 of 5) (presumably not all partial responses).

There are plans to conduct a phase 2 trial now that the MTD has been defined.

http://www.medscape.com/viewarticle/862131

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Ensartinib (X396) trial update

63 patients in trial but only 35 are ALK+, NSCLC, and treated at 200 to 250 mg daily.

Of those, 8 were ALK inhibitor naive, 7 (88%) had an objective response. 19 patients had received Crizotinib but not another ALK inhibitor, 16 ((84%) had demonstrated reductions in tumor size (unclear how many qualified as partial responses). That leaves 8 patients who presumably were treated with an ALK inhibitor other than or in addition to Crizotinib. No results were in the article for this last group. Responses have lasted as long as 30 months.

In patients with brain mets 63% (5 of 8) had some reduction in size.

http://www.businesswire.com/news/home/20160420005374/en/Xcovery-Presents-Data-Supporting-Potential-Efficacy-X-396

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Additional Brigatinib info

Ariad has posted a new presentation from European Lung Cancer Conference on their website for a limited time.

Pages 7-13 are most relevant. Page 8 shows a breakdown of how patients  responded by dose. 90 mg had a ORR of 77%; 90->180 mg had an ORR 79%; 180 mg had an ORR of 65%.

Page 9 has a PFS survival curve graph and a regular survival curve graph. Both show Crizotinib naive patients doing better than Crizotinib pretreated patients. Importantly both charts show a fair degree of plateauing in the curves after about 12 to 18 months and the plateaus are at relatively high levels. For example, a plateau for Crizotinib pretreated patients of over 70% surviving after 2 years. The plateaus look impressive, but I think each tick mark indicates a patient who left the study for unknown reasons (but probably many were moving on to other treatments). But the graphs do look better than graphs I have seen for other ALK inhibitors. If anyone knows more than I do about survival curves please correct me.

Page 10 looks at brain Mets and finds that the median brain PFS is 15.6 months. Pages 11-13 look at side effects of the drug.

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