Loralatinib phase II results

Posted on March 1, 2019 by admin

Published on 11-6-18, I believe in conjunction with the FDA approval. 276 ALK+ & ROS1+ patients. But only adverse events were reported for the ROS1 patients

The description of the results in the article I found was very confusing. The article said there were 6 cohorts but described 7. Then it reported results but it kept combining results from different cohorts in different combinations. Here are a few results that I could sort out.

For treatment naive patients, 90% had partial or complete responses & 66.7% had intracranial responses.

For patients who were treated with one or more ALK inhibitors, 47% had a partial or complete response and 29% had stable disease.  63% had an intracranial response.

Excess cholesterol and triglycerides were the most common side effects, but 18% reported cognitive effects.

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30649-1/fulltext

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

Patients can live a median of 6.8 years after stage 4 diagnosis

Posted on February 13, 2019 by admin

A study of 110 patients at the University of Colorado found that 50% of patients live 6.8 years or longer. These were patients who had access to multiple ALK inhibitors through clinical trials at that research University. That University also used Pemetrexed when patients were given chemotherapy.

However, most of those drugs are now FDA approved in some way or another.

https://www.ncbi.nlm.nih.gov/pubmed/30599201

With the right care, patients now living a median 6.8 years after stage IV ALK+ lung cancer diagnosis

 

 

Posted in alectinib - Alecensa from Chugai - Roche - GenenTech, brigatinib-Alunbrig from Takeda, ceritinib - Zykadia from Novartis, crizotinib - Xalkori from Pfizer, lorlatinib - Lorbrena by Pfizer, Lung cancer, Research | Leave a comment

Brigatinib vs Crizotinib phase 3 interim results

Posted on February 13, 2019 by admin

In September 2018, Takeda reported a pre-designated first interim analysis of a phase 3 trial in the New England Journal of Medicine. The study enrolled 275 ALK inhibitor naive patients. Half got Brigatinib and half got Crizotinib.

For Brigatinib: at 12 months the PFS was 67%, objective response rate was 71%, and intracranial response rate for patients with brain lesions was 78%.

For Crizotinib: at 12 months the PFS was 43%, objective response rate was 60%, and intracranial response rate for patients with brain lesions was 29%.

For 12 month PFS the P value was less than 0.001. Which means the chance that the results are completely wrong are 0.1%

https://www.ncbi.nlm.nih.gov/pubmed/30280657

Posted in Brain metastases, brigatinib-Alunbrig from Takeda, crizotinib - Xalkori from Pfizer, Lung cancer, Research | Leave a comment

FDA conditionally approves Loralatinib

Posted on November 3, 2018 by admin

As of 11-2-2018 the FDA conditionally approved Loralatinib. It’s brand name is Lorbrena.

The approval is for Loralatinib treatment for patients: 1) as a third line after crizotinib and one other ALK inhibitor (basically Brigatinib), or 2) as a second line treatment after either: A) Alectinib, or B) Ceritinib.

At this time Brigatinib has not been approved as a first line treatment by The FDA. Although a positive Phase 3 trial results were recently published.

The FDA approval is conditioned on a Phase 3 trial being completed. A description is posted on March 1, 2019 on this site.

https://www.pfizer.com/news/press-release/press-release-detail/u_s_fda_approves_lorbrena_lorlatinib_for_previously_treated_alk_positive_metastatic_nsclc

 

Posted in alectinib - Alecensa from Chugai - Roche - GenenTech, Brain metastases, brigatinib-Alunbrig from Takeda, ceritinib - Zykadia from Novartis, crizotinib - Xalkori from Pfizer, lorlatinib - Lorbrena by Pfizer, Lung cancer, Potential Treatments, Regulatory applications & approvals | Leave a comment

Impact of EML4-ALK Variants on resistance

Posted on June 15, 2018 by admin

As of April 20, 2018

Study of 2 groups of patients. Group A = 129 patients, Group B = 577 patients.

The most frequent variants were Variant 1 (43%) and Variant 3 (40%).

“ALK resistance mutations were significantly more common in variant 3 than in variant 1 (57% v 30%).”

“In particular, ALK 1202R was more common in variant 3 than in variant 1 (32% v 0%).”

“Among patients treated with the third-generation ALK TKI lorlatinib, variant 3 was associated with a significantly longer progression-free survival than variant 1.”

https://www.ncbi.nlm.nih.gov/pubmed/29373100

Posted in lorlatinib - Lorbrena by Pfizer, Lung cancer, Potential Treatments, Research, Resistance to treatment | Leave a comment

Pfizer files for FDA approval of lorlatinib

Posted on June 15, 2018 by admin

As of February 12, 2018

Pfizer filed a new drug application (NDA) for lorlatinib with the FDA, Japan, and Europe for use in patients with ALK-positive lung cancer. FDA’s decision is expected by the end of August.

In support of the 3 applications, Pfizer submitted data from the phase II part of a phase I/II trial in which the overall response rate (ORR) was 69% in ALK-positive patients previously treated with crizotinib (Xalkori) with or without chemotherapy, and the Intracranial ORR was 68%. See previous posts for more detail.

https://www.onclive.com/web-exclusives/fda-grants-priority-review-to-lorlatinib-for-alk-nsclc

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Liquid Biopsy can be used to track evolution of resistance

Posted on June 15, 2018 by admin

As of January 23, 2018 and March 29, 2018:

Plasma genotyping by Next Generation Sequencing (Liquid Biopsy) can be used to track evolution of resistance to various ALK inhibitors.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785105/

https://www.ncbi.nlm.nih.gov/pubmed/29599410

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FDA approves alectinib (Alecensa) as 1st line treatment

Posted on June 15, 2018 by admin

As of November 6, 2017

FDA approves alectinib (Alecensa) as 1st line treatment based on Phase 3 results.

The estimated median Progression Free Survival (PFS) for patients taking alectinib was 25.7 months, compared with 10.4 months for those taking crizotinib.

The Objective Response Rate (ORR) was 79% and 72%  in the alectinib and crizotinib arms, respectively.

Among the 120 responders in the alectinib arm and the 109 responders in the crizotinib arm, the proportion of patients with response duration of ≥12 months was 64% and 36%, respectively.

The Central Nervous System (CNS) ORR was 81% among patients taking alectinib and 50% among patients taking crizotinib.

Among patients with measurable CNS lesions and a CNS response, the proportion of patients with a CNS response duration of ≥12 months was 59% in the alectinib arm and 36% in the crizotinib arm.

https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm584082.htm

Posted in alectinib - Alecensa from Chugai - Roche - GenenTech, Brain metastases, Lung cancer, Potential Treatments, Regulatory applications & approvals | Leave a comment

Phase 1 & 2 full results for Lorlatinib

Posted on June 15, 2018 by admin

As of Oct. 16, 2017 Pfizer presented a Press release associated with a presentation at IASLC on Phase 2 results for 275 patients.

All following are for ALK+ patients except where Ros1 is indicated

Treatment Naive:  ORR 90%; IC-ORR 75%

Prior treatment with Crizotinib: ORR 69%; IC-ORR 68%

Prior treatment with ALK Inhibitor other than Crizotinib: ORR 33%; IC-ORR 42%

Prior treatment with 2+ ALK Inhibitors: ORR 39%; IC-ORR 48%

ROS1 + regardless of prior treatments: ORR 36%; IC-ORR 56%

ORR = Objective Response Rate

IC-ORR = Intracranial ORR

for more details from press release see: https://www.pfizer.com/news/press-release/press-release-detail/pfizer_presents_full_results_from_phase_2_study_of_next_generation_investigational_alk_inhibitor_lorlatinib_in_alk_positive_and_ros1_positive_advanced_non_small_cell_lung_cancer

 

As of Dec. 2017 an article was published of Phase 1 results for 54 patients

For all 41 ALK+ patients the ORR was 46%

For 26 ALK+ patients that received 2+ ALK Inhibitors the ORR was 42%

For 12 ROS1 +patients the ORR was 50%

For published article see also https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(17)30680-0.pdf

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

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

Posted on June 16, 2017 by admin

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 alectinib - Alecensa from Chugai - Roche - GenenTech, Brain metastases, brigatinib-Alunbrig from Takeda, ceritinib - Zykadia from Novartis, crizotinib - Xalkori from Pfizer, lorlatinib - Lorbrena by Pfizer, Lung cancer, Potential Treatments | Leave a comment