Thoracic Neoplasm

Development of second generation ALK inhibitors has been underway in order to address resistance to first line treatments such as crizotinib in ALK-rearranged NSCLC. Brigatinib is a potent dual inhib… (full text at CIViC)

PMID 26951079 · Wu et al., 2016 · Open in CIViC

In a phase II randomized trial we evaluated two regimens of Brigatinib in Crizotinib-refractory ALK-pos. NSCLC. They were randomly assigned (1:1) to oral Brigatinib 90 mg once daily (arm A) or 180 mg … (full text at CIViC)

PMID 28475456 · Kim et al., 2017 · Open in CIViC

A single-arm, open-label, phase 1/2 trial showed that 51 (72% [60-82]) out of 71 patients with crizotinib-treated and crizotinib-naive ALK-rearranged NSCLC responded to the ALK inhibitor, Brigatinib.

PMID 27836716 · Gettinger et al., 2016 · Open in CIViC

In a phase 3 trial, patients with previously treatmented NSCLC with ALK fusion were randomly assigned to ceritinib or chemotherapy. Ceritinib showed a significant improvement in median PFS compared w… (full text at CIViC)

PMID 28602779 · Shaw et al., 2017 · Open in CIViC

In a phase 3 trial (ASCEND-4, NCT01828099), a comparison of the selective ALK inhibitor ceritinib (750 mg daily) to chemotherapy (cisplatin or carboplatin plus pemetrexed) in 376 untreated ALK-fusion… (full text at CIViC)

PMID 28126333 · Soria et al., 2017 · Open in CIViC

Updated results from ASCEND-1 trial assessing safety and activity of ceritinib in ALK rearranged locally advanced or metastatic NSCLC. 255 patients were enrolled and received at least one dose of ceri… (full text at CIViC)

PMID 26973324 · Kim et al., 2016 · Open in CIViC

This dose escalation phase 1 study examined the safety and efficacy of ceritinib in 122 NSCLC patients harboring ALK rearrangements (determined by break-apart FISH). Maximum tolerated dose (MTD) was d… (full text at CIViC)

PMID 24670165 · Shaw et al., 2014 · Open in CIViC

In the Phase I study PROFILE 1001 (NCT00585195), a recommended crizotinib dose of 250 mg twice daily for 28 day cycles was established. Among 1,500 advanced NSCLC patients who were screened for ALK-re… (full text at CIViC)

PMID 20979469 · Kwak et al., 2010 · Open in CIViC

This two arm Phase III study named PROFILE 1007 (NCT00932893) was performed to assess crizotinib vs. established chemotherapy in non-small cell lung cancer patients positive for ALK rearrangement (ass… (full text at CIViC)

PMID 23724913 · Shaw et al., 2013 · Open in CIViC

This phase 3 trial named PROFILE 1014 (NCT01154140) compared crizotinib to established chemotherapy in first-line treatment for this disease. The study consisted of 343 patients with advanced or metas… (full text at CIViC)

PMID 25470694 · Solomon et al., 2014 · Open in CIViC

This retrospective study of patients from the PROFILE 1001 and 1005 studies of crizotinib in advanced ALK-rearranged NSCLC assessed the potential benefit of crizotinib beyond progressive disease (CBPD… (full text at CIViC)

PMID 24478318 · Ou et al., 2014 · Open in CIViC

This prospective Phase III study named Profile 1014 on NSCLC ALK-rearranged patients assessed intracranial disease control rate (IC-DCR) in the subset of patients entering the study with preexisting t… (full text at CIViC)

PMID 27022118 · Solomon et al., 2016 · Open in CIViC

In a retrospective study comparing survival outcomes in a subgroup of 82 ALK-positive crizotinib-treated patients enrolled in a phase 1 clinical trial (NCT00585195), crizotinib therapy was associated … (full text at CIViC)

PMID 21933749 · Shaw et al., 2011 · Open in CIViC

A phase-3 clinical trial evaluated 347 patients with ALK-positive lung cancer. The study compared crizotinib treatment (n=173) with chemotherapy treatment of either pemetrexed or docetaxel (n=174). … (full text at CIViC)

PMID 26466010 · 2015 · Open in CIViC

In an evaluation of a patient with crizotinib-sensitive lung adenocarcinoma, an EML4-ALK-E13;A20 rearrangement was identified using CGP. The patient attained a reduction in the target lesions by 14.2… (full text at CIViC)

PMID 25922291 · Le et al., 2015 · Open in CIViC

In a randomized, open-label phase 3 trial 303 patients with ALK-positive, previously untreated NSCLC (including asympt. CNS disease) were randomized to reiceive either Alectinib or Crizotinib. During … (full text at CIViC)

PMID 28586279 · Peters et al., 2017 · Open in CIViC

In a phase 3 trial (CROWN, NCT03052608), a comparison of the selective third generation ALK inhibitor lorlatinib to the first generation ALK inhibitor crizotinib in 296 untreated ALK-fusion positive… (full text at CIViC)

PMID 33207094 · Shaw et al., 2020 · Open in CIViC

In a phase 2 trial, patients with NSCLC with ALK fusion received lorlatinib. In treatment-naive patients, ORR was 90.0% In patients with at least one previous ALK tyrosine kinase inhibitor, ORR were a… (full text at CIViC)

PMID 30413378 · Solomon et al., 2018 · Open in CIViC

A phase 2 trial of 228 ALK-positive NSCLC with or without previous chemotherapy treatment found lorlatinib to be effective in ALK inhibitor treatment-naive NSCLC as well as following treatment with on… (full text at CIViC)

PMID 30413378 · Solomon et al., 2018 · Open in CIViC

In a post hoc analysis of the phase 3 trial (CROWN, NCT03052608) comparing the selective third generation ALK inhibitor lorlatinib to the first generation ALK inhibitor crizotinib in ALK-fusion posit… (full text at CIViC)

PMID 35605188 · Solomon et al., 2022 · Open in CIViC

Among 95 patients with NSCLC in this study, 15 had an ALK translocation. ORR of these patients compared to EGFR mutated or wild-type tumors was superior (46.7 versus 4.7 versus 16.2%, p = 0.001). TYMS… (full text at CIViC)

PMID 21642865 · Lee et al., 2011 · Open in CIViC

In this study, heavily pretreated advanced NSCLC patients with various molecular tumor makeup were treated with Hsp90 inhibitor IPI-504 to assess overall response rate. The study did not reach the tar… (full text at CIViC)

PMID 20940188 · Sequist et al., 2010 · Open in CIViC

In a stage IV lung adenocarcinoma patient, ALK I1171N was associated with acquired resistance to crizotinib monotherapy. An ALK gene rearrangement had been previously identified and was associated wi… (full text at CIViC)

PMID 27565911 · Johnson et al., 2016 · Open in CIViC

A case study of a 58 year old woman with ALK-rearranged NSCLC found the resistance mutation L1196M following treatment with crizotinib and alectinib. Treatment with ceritinib resulted in tumour regres… (full text at CIViC)

PMID 29796191 · Makuuchi et al., 2018 · Open in CIViC

In a prospective study (NCT01283516) of 130 cancer patients, non-small cell lung cancer patients (n=2) harboring a L1196M mutation in the ALK portion of the ALK rearrangement were associated with a 50… (full text at CIViC)

PMID 24670165 · Shaw et al., 2014 · Open in CIViC

On December 4, 2024, the Food and Drug Administration granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with advanced, unresectable, or metastatic non-small cell lun… (full text at CIViC)

PMID 39908431 · Schram et al., 2025 · Open in CIViC

1378 cases of NSCLC were screened. One patient (frequency 0.1%) with a NTRK1 gene rearrangement (SQSTM1-NTRK1 Fusion) was treated with entrectinib in a phase 1 study. The patient had resolution of pri… (full text at CIViC)

PMID 26565381 · Farago et al., 2015 · Open in CIViC

Two patients were found to harbor gene fusions maintaining the kinase domain of NTRK1 (3' partner), specifically: MPRIP-NTRK1 and CD74-NTRK1. Both of these fusions lead to constitutive kinase activit… (full text at CIViC)

PMID 24162815 · Vaishnavi et al., 2013 · Open in CIViC

Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. 4 patients with metastatic RET-rearranged NSCLC were identified. 3 of 4 had receive… (full text at CIViC)

PMID 27544060 · Lin et al., 2016 · Open in CIViC

RET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with … (full text at CIViC)

PMID 27825636 · Drilon et al., 2016 · Open in CIViC

In this phase II trial, 404 patients with advanced NSCLC underwent ROS1 pre-screening, and 32 patients with ROS1 rearrangement confirmed with FISH were enrolled. All patients except two were crizotini… (full text at CIViC)

PMID 28520527 · Lim et al., 2017 · Open in CIViC

In the ongoing phase 1 study PROFILE 1001, NSCLC patients with ROS1 rearrangement confirmed by FISH or RT-PCR received crizotinib 250mg twice daily. Among 53 patients, the ORR was 72% (95% CI, 58% to … (full text at CIViC)

PMID 30980071 · Shaw et al., 2019 · Open in CIViC