NCT02706626

Trial of Brigatinib After Treatment With Next-Generation ALK Inhibitors

Terminated Phase 2 Results posted Last updated 26 January 2023

What this trial tests

Phase 2 trial testing brigatinib in Non-Small Cell Lung Cancer in 32 participants. Terminated before completion.

Timeline

9 March 2017

Primary endpoint
8 October 2020

1 April 2021

Quick facts

Lead sponsor	Criterium, Inc.
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	32
Start date	9 March 2017
Primary completion	8 October 2020
Estimated completion	1 April 2021
Sites	4 locations across United States

Drugs / interventions tested

• brigatinib (brigatinib) — full drug profile →

Conditions studied

• Non-Small Cell Lung Cancer — all drugs for Non-Small Cell Lung Cancer →

Sponsor

Criterium, Inc. — full company profile →

Who can join

18 and older, any sex, with Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate Primary · Through study completion (average 42 months)

An assessment of the response using RECIST 1.1 per investigator. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.". The enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results

Group	Value	95% CI
Arm A: Brigatinib After Next Generation ALK TKI Regardless of Number of Therapies	9
Arm B: Brigatinib After First-line Therapy With Alectinib	1
Arm C: Brigatinib 240 mg in Patient With Disease Progression on Brigatinib 180 mg Daily	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Patients were followed until disease progression or unacceptable toxicity or withdrawal of consent, on average 1 year. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A: Brigatinib After Next Generation ALK TKI

Serious: 8/27 (30%)

Deaths: 10/27

Arm B: Brigatinib After First-line Alectinib

Serious: 2/4 (50%)

Deaths: 1/4

Arm C: Brigatinib 240 mg in Patients With Disease Progression on Brigatinb

Serious: 2/4 (50%)

Deaths: 1/4

Serious adverse events (5 terms)

Reaction	System	Arm A: Brigatinib After Ne…	Arm B: Brigatinib After Fi…	Arm C: Brigatinib 240 mg i…
Pneumonitis, pleural effusion,hemoptysis	Respiratory, thoracic and mediastinal disorders	—	—	—
Increased CPK	Investigations	—	—	—
Seizure	Nervous system disorders	—	—	—
Muscle or bone pain	Musculoskeletal and connective tissue disorders	—	—	—
Sepsis	Infections and infestations	—	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Arm A: Brigatinib After Ne…	Arm B: Brigatinib After Fi…	Arm C: Brigatinib 240 mg i…
Cough, shortness of breath, dsypnea, upper respiratory infection	Respiratory, thoracic and mediastinal disorders	—	—	—
Increased creatinine	Renal and urinary disorders	—	—	—
Lab abnormalities	Investigations	—	—	—
Anrorexia fatigue,	General disorders	—	—	—
Headaches, dizzimes	Nervous system disorders	—	—	—

Most-reported serious reactions: Pneumonitis, pleural effusion,hemoptysis, Increased CPK, Seizure, Muscle or bone pain, Sepsis.

Data from ClinicalTrials.gov NCT02706626 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety and effectiveness of this investigational drug, brigatinib (AP261136) in patients with advanced non-small cell lung cancer Non-small cell lung cancer (NSCLC) who have had first-line treatment for their cancer and it still got worse, even after, or while taking drugs called ALK inhibitors, or anti-cancer drugs that act on tumors. Some examples of these anti-cancer drugs are: KEYTRUDA® or ALECENSA®).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends.
   Majeed U, Manochakian R, Zhao Y, Lou Y. · · 2021 · cited 193× · PMID 34238332 · DOI 10.1186/s13045-021-01121-2
2. New Insights Into the Role of Phenotypic Plasticity and EMT in Driving Cancer Progression.
   Bhatia S, Wang P, Toh A, Thompson EW. · · 2020 · cited 63× · PMID 32391381 · DOI 10.3389/fmolb.2020.00071
3. Brigatinib in Patients With Alectinib-Refractory ALK-Positive NSCLC.
   Lin JJ, Zhu VW, Schoenfeld AJ, Yeap BY, et al · · 2018 · cited 62× · PMID 29935304 · DOI 10.1016/j.jtho.2018.06.005
4. Therapeutic Sequencing in ALK⁺ NSCLC.
   Elsayed M, Christopoulos P. · · 2021 · cited 48× · PMID 33494549 · DOI 10.3390/ph14020080
5. The activity, safety, and evolving role of brigatinib in patients with <i>ALK</i>-rearranged non-small cell lung cancers.
   Sabari JK, Santini FC, Schram AM, Bergagnini I, et al · · 2017 · cited 44× · PMID 28435288 · DOI 10.2147/ott.s109295
6. Safety and efficacy of anaplastic lymphoma kinase tyrosine kinase inhibitors in non‑small cell lung cancer (Review).
   Wang L, Wang W. · · 2021 · cited 42× · PMID 33200229 · DOI 10.3892/or.2020.7851
7. Targeting ALK Rearrangements in NSCLC: Current State of the Art.
   Peng L, Zhu L, Sun Y, Stebbing J, et al · · 2022 · cited 39× · PMID 35463328 · DOI 10.3389/fonc.2022.863461
8. ALK inhibitors, resistance development, clinical trials.
   Rothenstein JM, Chooback N. · · 2018 · cited 34× · PMID 29910648 · DOI 10.3747/co.25.3760