2022
Long-Term Efficacy and Safety of Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Final Results of the Phase 1/2 and Randomized Phase 2 (ALTA) Trials
Gettinger SN, Huber RM, Kim DW, Bazhenova L, Hansen KH, Tiseo M, Langer CJ, Rodríguez L, West HL, Reckamp KL, Weiss GJ, Smit EF, Hochmair MJ, Kim SW, Ahn MJ, Kim ES, Groen HJM, Pye J, Liu Y, Zhang P, Vranceanu F, Camidge DR. Long-Term Efficacy and Safety of Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Final Results of the Phase 1/2 and Randomized Phase 2 (ALTA) Trials. JTO Clinical And Research Reports 2022, 3: 100385. PMID: 36065449, PMCID: PMC9440305, DOI: 10.1016/j.jtocrr.2022.100385.Peer-Reviewed Original ResearchProgression-free survivalPhase 1/2 studyMedian investigator-assessed progression-free survivalInvestigator-assessed progression-free survivalMedian overall survivalPhase 2 trialLong-term efficacyOverall survivalPhase 1/2Arm AStudy endMedian intracranial progression-free survivalIntracranial progression-free survivalRandomized phase 2 trialNew safety signalsIndependent review committeeArm B.Advanced malignanciesBrain metastasesManageable safetyArm BPositive NSCLCSafety signalsNSCLCPatientsAssociation of depth of target lesion response to brigatinib with outcomes in patients with ALK inhibitor-naive ALK+ NSCLC in ALTA-1L.
Camidge D, Kim H, Ahn M, Yang J, Han J, Hochmair M, Lee K, Delmonte A, Campelo R, Kim D, Griesinger F, Felip E, Califano R, Spira A, Thomas M, Gettinger S, Tiseo M, Liu Y, Zhang P, Popat S. Association of depth of target lesion response to brigatinib with outcomes in patients with ALK inhibitor-naive ALK+ NSCLC in ALTA-1L. Journal Of Clinical Oncology 2022, 40: 9072-9072. DOI: 10.1200/jco.2022.40.16_suppl.9072.Peer-Reviewed Original ResearchBlinded independent review committeeTarget lesion assessmentTarget lesion responseLesion shrinkageLesion responseLesion assessmentCochran-Armitage trend analysisRandomized phase 3 trialShrinkage groupPhase 3 trialDepth of responseIndependent review committeeLonger median timeMajority of ptsAssociation of depthRECIST v1.1PFS eventsMedian ageOS ratesMedian timeStudy endTarget lesionsLower riskDeep responsesBrigatinib
2021
Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial
Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira AI, Gettinger SN, Tiseo M, Lin HM, Liu Y, Vranceanu F, Niu H, Zhang P, Popat S. Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. Journal Of Thoracic Oncology 2021, 16: 2091-2108. PMID: 34537440, DOI: 10.1016/j.jtho.2021.07.035.Peer-Reviewed Original ResearchConceptsBlinded independent review committeeIndependent review committeeBrain metastasesSurvival benefitSuperior efficacyTP53 mutationsAdvanced ALK-positive NSCLCBaseline brain metastasesSecondary ALK mutationsMedian overall survivalOverall survival benefitPrimary end pointNew safety signalsPhase 3 studyALK-positive NSCLCLung cancer trialsPlasma cell-free DNAPoor prognostic biomarkerReview CommitteeEML4-ALK variantsCell-free DNAAdvanced ALKOverall survivalPoor PFSPositive NSCLCBrigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): Final results of the phase 1/2 and phase 2 (ALTA) trials.
Gettinger S, Huber R, Kim D, Bazhenova L, Hansen K, Tiseo M, Langer C, Paz-Ares L, West H, Reckamp K, Weiss G, Smit E, Hochmair M, Kim S, Ahn M, Kim E, Groen H, Pye J, Vranceanu F, Camidge D. Brigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): Final results of the phase 1/2 and phase 2 (ALTA) trials. Journal Of Clinical Oncology 2021, 39: 9071-9071. DOI: 10.1200/jco.2021.39.15_suppl.9071.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalPhase 1/2 studyIndependent review committeeArm A/BPhase 2 trialOverall survivalPhase 1/2Arm AKaplan-MeierRefractory non-small cell lung cancerMetastatic non-small cell lung cancerHigher median progression-free survivalMedian progression-free survivalTreatment-emergent adverse eventsALK tyrosine kinase inhibitorsKinase inhibitorsBaseline brain metastasesObjective response rateOpen-label trialNew safety signalsCell lung cancerDuration of responseTreatment of patientsLong-term efficacy
2020
Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial
Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Campelo M, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. Journal Of Clinical Oncology 2020, 38: 3592-3603. PMID: 32780660, PMCID: PMC7605398, DOI: 10.1200/jco.20.00505.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerALK-positive non-small cell lung cancerProgression-free survivalBlinded independent review committeeCell lung cancerInterim analysisLung cancerAdvanced ALK-positive non-small cell lung cancerGlobal health status/QoL scoreNext-generation anaplastic lymphoma kinase (ALK) inhibitorPositive non-small cell lung cancerPredictors of PFSPromising first-line treatmentSecond prespecified interim analysisSuperior progression-free survivalPlasma concentration-time curveAnaplastic lymphoma kinase inhibitorsPrespecified interim analysisPrimary end pointSecond interim analysisFirst-line treatmentFirst interim analysisHealth-related qualityIndependent review committeePatient-reported outcomes
2019
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial
Huber RM, Hansen KH, Paz-Ares Rodríguez L, West HL, Reckamp KL, Leighl NB, Tiseo M, Smit EF, Kim DW, Gettinger SN, Hochmair MJ, Kim SW, Langer CJ, Ahn MJ, Kim ES, Kerstein D, Groen HJM, Camidge DR. Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial. Journal Of Thoracic Oncology 2019, 15: 404-415. PMID: 31756496, DOI: 10.1016/j.jtho.2019.11.004.Peer-Reviewed Original ResearchConceptsProgression-free survivalObjective response rateIntracranial objective response rateOverall survivalIntracranial PFSResponse rateEnd pointIntracranial responseBrain lesionsCentral nervous system metastasesSolid Tumors version 1.1Intracranial progression-free survivalCrizotinib-refractory patientsMedian overall survivalNervous system metastasesNew safety findingsPrimary end pointSecondary end pointsTarget lesion responseResponse Evaluation CriteriaIndependent review committeeDepth of responseImportant end pointIntracranial outcomesOral brigatinibLBA1 Brigatinib vs crizotinib in patients with ALK inhibitor-naive advanced ALK+ NSCLC: Updated results from the phase III ALTA-1L trial
Camidge R, Kim H, Ahn M, Yang J, Han J, Hochmair M, Lee K, Delmonte A, Campelo M, Kim D, Griesinger F, Felip E, Califano R, Spira A, Gettinger S, Tiseo M, Ni Q, Zhang P, Popat S. LBA1 Brigatinib vs crizotinib in patients with ALK inhibitor-naive advanced ALK+ NSCLC: Updated results from the phase III ALTA-1L trial. Annals Of Oncology 2019, 30: ix195-ix196. DOI: 10.1093/annonc/mdz446.Peer-Reviewed Original ResearchBrain metastasesPFS eventsTakeda Pharmaceutical Company LimitedPrior chemotherapyBoehringer IngelheimInterim analysisARIAD PharmaceuticalsGuardant HealthPFS HREli LillyBlinded independent review committeeClovis OncologyAdditional efficacy dataAsymptomatic CNS metastasesBaseline brain metastasesECOG PS 0Measurable brain metastasesObjective response rateProgression-free survivalSecond interim analysisPatient-reported qualityDuration of responseIndependent review committeeRoche/GenentechBristol-Myers Squibb1543P Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase II ALTA trial
Lee D, Kim D, Camidge D, Langer C, Huber R, Tiseo M, West H, Groen H, Reckamp K, Hochmair M, Leighl N, Hansen K, Gettinger S, Paz-Ares L, Kim E, Smit E, Kim S, Ni Q, Zhang P, Ahn M. 1543P Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase II ALTA trial. Annals Of Oncology 2019, 30: v634-v635. DOI: 10.1093/annonc/mdz260.065.Peer-Reviewed Original ResearchBristol-Myers SquibbCNS metastasesTakeda Pharmaceutical Company LimitedBoehringer IngelheimARIAD PharmaceuticalsClovis OncologyRoche/GenentechEli LillyMerck SharpBaseline CNS metastasesIntracranial objective responseMost common gradeObjective response rateProgression-free survivalDuration of responseIndependent review committeeNon-Asian patientsPierre FabreMedian DoRMedian iPFSMedian PFSRECIST v1.1Objective responseOverall survivalMedian ageO1-4-2 [Encore] Brigatinib (BRG) vs Crizotinib (CRZ) in Patients (Pts) With ALK Inhibitor-Naive Advanced ALK+ NSCLC from ALTA-1L
Yang J, Kim H, Ahn M, Han J, Hochmair M, Lee K, Delmonte A, Campelo M, Kim D, Felip E, Califano R, Spira A, Gettinger S, Tiseo M, Haney J, Kerstein D, Popat S, Camidge D. O1-4-2 [Encore] Brigatinib (BRG) vs Crizotinib (CRZ) in Patients (Pts) With ALK Inhibitor-Naive Advanced ALK+ NSCLC from ALTA-1L. Annals Of Oncology 2019, 30: vi83. DOI: 10.1093/annonc/mdz339.006.Peer-Reviewed Original ResearchIntracranial ORRInterim analysisPFS eventsBlinded independent review committeeAsymptomatic CNS metastasesBaseline brain metastasesMost common gradeSecondary efficacy endpointsFirst interim analysisIndependent review committeeCNS metastasisMedian iPFSMedian PFSPrior chemotherapyAdvanced diseaseEfficacy endpointPrimary endpointBrain metastasesData cutoffSystemic therapyALK-TKIMedian ageMulticenter studyCommon gradeCrizotinib
2018
Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials.
Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, Huber RM, Hochmair MJ, Lee DH, Bazhenova LA, Gold KA, Ou SI, West HL, Reichmann W, Haney J, Clackson T, Kerstein D, Gettinger SN. Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials. Journal Of Clinical Oncology 2018, 36: 2693-2701. PMID: 29768119, DOI: 10.1200/jco.2017.77.5841.Peer-Reviewed Original ResearchConceptsIntracranial progression-free survivalBaseline brain metastasesALK-positive NSCLCBrain metastasesIntracranial ORRArm ALung cancerAnaplastic Lymphoma Kinase-Positive NonMedian intracranial progression-free survivalPhase I/II trialNext-generation ALK inhibitorsSmall cell lung cancerMeasurable brain metastasesPrior brain radiotherapyResults Most patientsPrimary end pointProgression-free survivalCell lung cancerIndependent review committeeInitial disease progressionAnaplastic lymphoma kinase (ALK) geneIntracranial efficacyII trialPrior radiationBrain radiotherapy
2017
Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial.
Ou S, Tiseo M, Camidge D, Ahn M, Huber R, Hochmair M, Kim S, West H, Reckamp K, Molina J, Liu G, Delmonte A, Viteri Ramirez S, Bearz A, Summers Y, Reichmann W, Kerstein D, Gettinger S, Kim D. Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial. Journal Of Clinical Oncology 2017, 35: e20502-e20502. DOI: 10.1200/jco.2017.35.15_suppl.e20502.Peer-Reviewed Original ResearchNon-small cell lung cancerBaseline brain metastasesBrain metastasesIndependent review committeeIntracranial efficacyCommon treatment-emergent adverse eventsNext-generation ALK inhibitorsTreatment-emergent adverse eventsFirst disease progressionCell lung cancerBlood CPKNSCLC ptsAdverse eventsAcceptable safetyLung cancerDisease progressionIntracranial responseALK inhibitorsBrigatinibMetastasisReview CommitteeGood responseEfficacyTrialsHypertensionDesign of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
Tiseo M, Popat S, Gettinger S, Peters S, Haney J, Kerstein D, Camidge D. Design of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2017, 35: tps9098-tps9098. DOI: 10.1200/jco.2017.35.15_suppl.tps9098.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalObjective response rateRandomized phase 3 trialPhase 3 trialPrimary endpointTKI therapyPositive non-small cell lung cancerAdvanced anaplastic lymphoma kinaseNext-generation ALK inhibitorsRandomized phase 2 trialPrior TKI therapySafety/tolerabilityPhase 1/2 trialPhase 2 trialKaplan-Meier methodCell lung cancerDuration of responseIndependent review committeeLog-rank testPotent preclinical activityTyrosine kinase inhibitorsAnaplastic lymphoma kinaseNaive patientsNSCLC pts