Great page with very high quality info on AlK & AlK inhibitors

Below is a link to a page that provides comprehensive regularly updated info written by two ALK research oncologists Dr. Alice Shaw and Ben Solomon, Phd (then edited by three people). It is written for an audience of doctors and other professionals so it can get technical, but generally I believe most people will be able to understand the key ideas.

https://www.uptodate.com/contents/anaplastic-lymphoma-kinase-alk-fusion-oncogene-positive-non-small-cell-lung-cancer

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

Roche at ASCO with Alectinib findings

Roche (Genentech) announced on June 6, 2017 at the 2017 ASCO conference that the have results from their first line Phase 3 Global Trial that Alectinib had a median PFS of 25.7 months vs 10.4 months for Crizotinib (over a year longer). The trial also found that Alectinib reduced the risk of cancer progression or death by 53% vs. Crizotinib. Furthermore, at 12 months the incidence of brain metastases was 9% for Alectinib and 41% for Crizotinib. Serious side effects were marginally better with Alectinib.

These results compliment earlier results from a Japan only trial and are likely to be the basis of FDA Application to move Alectinib to the first line setting.

I strongly recommend reading the New England Journal of Medicine (NEJM) article. The charts on page 6 are particularly persuasive.

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1704795

http://www.onclive.com/web-exclusives/alectinib-beats-crizotinib-in-frontline-alk-nsclc-alex-trial

 

Posted in alectinib - Alecensa from Chugai - Roche - GenenTech, Brain metastases, crizotinib - Xalkori from Pfizer, Lung cancer, Potential Treatments, Research | Leave a comment

Zykadia (ceritinib) by Novartis is approved for first line use in US

As of May 26, 2017 the FDA approved ceritinib for first line use. So it will go head to head with crizotinib. One article said a similar EU approval was likely “in coming weeks”.

The results are based on the phase 3 ASCEND-4 trial which found that in the first line setting that patients who took  ceritinib had a median progression-free survival of 16.6 months vs. 8.1 months on Pemetrexed platinum chemotherapy.

https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-expanded-use-zykadiar-first-line-alk-positive

 

Posted in Brain metastases, ceritinib - Zykadia from Novartis, Lung cancer, Potential Treatments, Regulatory applications & approvals, Research | Leave a comment

FDA approves brigatinib

On April 28, 2017 the FDA granted Takeda (formerly Ariad) approval for Alunbrig (brigatinib) to be sold in the US to patients who are resistant to Crizotinib.

Posted in AP26113 - brigatinib from Ariad, Lung cancer, Potential Treatments, Regulatory applications & approvals | Leave a comment

Lorlatinib granted breakthrough therapy status

On April 27, 2017, the FDA granted Pfizer Breakthrough Status on lorlatinib for patients previously treated with one or more ALK inhibitors. So you don’t have to take Crizotinib first, any of the other 3 will do. Also a Phase 3 CROWN study (NCT03052608) has begun enrolling patients.

Posted in 3922 - lorlatinib by Pfizer, Brain metastases, Lung cancer, Potential Treatments, Research | Leave a comment

Clinical Trial of PLB1003 by Beijing Pearl Biotechnology

As of April 19, 2017 ClinicalTrials.gov lists a phase 1 trial of PLB1003 which targets ALK. At this time the trial is at one site: Shanghai Chest Hospital.

To qualify you must have one measurable met in the body.

The trial identifier is: NCT03130881.

Posted in Lung cancer, PLB1003 - Beijing Pearl Biotechnology, Potential Treatments, Research | Leave a comment

Clinical trial of TPX-0005 from TP Therapeutics

As of March 6, 2017, ClinicalTrials.gov lists a Trial of TPX-0005 which targets ALK, ROS1, and NTRK 1-3. At this time there are four trial sites at: UC Irvine Cancer center, University of Colorado, Denver, Massachusetts General Hospital, and Memorial Sloan Kettering.

The trial does cover patients with regular body measurable mets and only measurable brain mets.

The trial identifier is NCT03093116.

Posted in Brain metastases, Lung cancer, Potential Treatments, Research, TPX-0005: TP Therapeutics | Leave a comment

Ariad files FDA application and gets acquired

As of August 30, 2016 Arriad had filed its new drug application with the FDA for brigatinib. As of Oct 31, 2016 the FDA granted ARIAD’s request for Priority Review and has set an action date of April 29, 2017.

As of January 9, 2017 Ariad agreed to be bought by Takeda Pharmaceutical Company Limited, a Japanese company. The merger is expected to close by the end of February 2017.

http://investor.ariad.com/phoenix.zhtml?c=118422&p=irol-news&nyo=0

Posted in AP26113 - brigatinib from Ariad, Lung cancer, Regulatory applications & approvals | Leave a comment

Update on Novartis and Ariad trials

As of Dec. 6, 2016 Novartis and Ariad announced research updates

In Phase III study by Novartis on Zykadia® (ceritinib) as a first-line treatment, they found a 45% reduction in the risk of disease progression. The study found a median progression free survival (PFS) of 16.6 months for all patients taking ceritinib, compared with 8.1 months for patients treated using just chemotherapy.  Also reported an ORR of 72.5%, compared with 26.7% for chemotherapy patients. Patients with no brain metastases had a median PFS of 26.3 months with Zykadia compared with 8.3 months for standard chemotherapy.

Ariad had positive info from a Phase I/II study and a pivotal phase 3 ALTA trial studying brigatinib, in patients with brain metastases.  Patients with brain mets had an ORR was 53% in the Phase I/II trial.

The patients previously treated with Crizotinib and with brain mets had an ORR of 67% in the higher dose arm B of the ALTA trial. Median brain mets PFS in Arm B was 18.4 months.

http://www.genengnews.com/gen-news-highlights/novartis-and-ariad-separately-report-positive-alk-inhibitor-results/81253504

Posted in Anaplastic Large-Cell Lymphomas, AP26113 - brigatinib from Ariad, Brain metastases, ceritinib - Zykadia from Novartis, Lung cancer, Potential Treatments, Research | Leave a comment

Abstract 9007 on Brigatinib update

The initial write up of the abstract 9007 was posted on May 19.

This update covers about 3 more months of data and brain mets.

Arm A (90 mg) median Progression Free Survival (PFS) increased from 8.8 months to 9.2 months. For arm B (180 mg) the median PFS increased from 11.1 months to 12.9 months. Probability of overall survival at 1 year was 71% for arm A and 80% for arm B.

For patients with measurable brain mets at baseline, for arm A the Objective Response Rate was 36% and for arm B the ORR was 67%. Median intracranial PFS was 15.6 months for arm A and not yet reached for arm B.

There is a press release on this topic on Ariad’s website.

Posted in AP26113 - brigatinib from Ariad, Brain metastases, Lung cancer, Potential Treatments, Research | Leave a comment