2022
Results from the phase 1/2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC).
Krop I, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Iwata H, Toyama T, Yamamoto Y, Hansra D, Takahashi M, Osaki A, Koyama K, Inoue T, Yonekura T, Mostillo J, Ohwada S, Tanaka Y, Sternberg D, Yonemori K. Results from the phase 1/2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC). Journal Of Clinical Oncology 2022, 40: 1002-1002. DOI: 10.1200/jco.2022.40.16_suppl.1002.Peer-Reviewed Original ResearchMetastatic breast cancerAntibody-drug conjugatesAnti-HER3 monoclonal antibodyInvestigational antibody-drug conjugateTopoisomerase I inhibitor payloadWhite blood cell countDose-finding portionGrade 5 eventsMedian treatment durationPhase 1/2 studyInterstitial lung diseaseBlood cell countMedian study durationECOG PSData cutoffDose expansionCentral adjudicationMetastatic diseaseNeutrophil countPrior linesMedian agePhase 1/2Platelet countSafety profileLung disease
2020
Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer
Tolaney SM, Barroso-Sousa R, Keenan T, Li T, Trippa L, Vaz-Luis I, Wulf G, Spring L, Sinclair NF, Andrews C, Pittenger J, Richardson ET, Dillon D, Lin NU, Overmoyer B, Partridge AH, Van Allen E, Mittendorf EA, Winer EP, Krop IE. Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer. JAMA Oncology 2020, 6: 1598-1605. PMID: 32880602, PMCID: PMC7489368, DOI: 10.1001/jamaoncol.2020.3524.Peer-Reviewed Original ResearchConceptsProgression-free survivalObjective response rateTumor-infiltrating lymphocytesTumor mutational burdenPD-L1 statusOverall survivalHormonal therapyPrior linesPD-L1Clinical trialsMedian numberDay 1Cell death ligand 1 (PD-L1) inhibitorsERBB2-negative metastatic breast cancerMedian progression-free survivalDeath ligand 1 (PD-L1) inhibitorsEnd pointCause adverse eventsEfficacy of eribulinHormone receptor positiveMulticenter phase 2PD-L1 22C3Treatment-related deathsLines of chemotherapyPrimary end pointTumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer
Barroso-Sousa R, Keenan TE, Pernas S, Exman P, Jain E, Garrido-Castro AC, Hughes M, Bychkovsky B, Umeton R, Files JL, Lindeman NI, MacConaill LE, Hodi FS, Krop IE, Dillon D, Winer EP, Wagle N, Lin NU, Mittendorf EA, Van Allen EM, Tolaney SM. Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2020, 26: 2565-2572. PMID: 32019858, PMCID: PMC7269810, DOI: 10.1158/1078-0432.ccr-19-3507.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerHigh tumor mutational burdenProgression-free survivalTumor mutational burdenObjective response rateImmune checkpoint inhibitorsAnti-PD-1/L1 therapyTriple-negative breast cancerOverall survivalL1 therapyPD-L1Breast cancerMutational burdenLow objective response rateLonger progression-free survivalShorter progression-free survivalDana-Farber Cancer InstituteTumor genomic featuresShorter overall survivalMutations/megabaseCheckpoint inhibitorsVisceral metastasesL1 blockadePerformance statusPrior linesA phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC).
Waks A, Keenan T, Li T, Tayob N, Wulf G, Richardson E, Mittendorf E, Overmoyer B, Krop I, Winer E, Van Allen E, Agudo J, Tolaney S. A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC). Journal Of Clinical Oncology 2020, 38: 1046-1046. DOI: 10.1200/jco.2020.38.15_suppl.1046.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalAdverse eventsT-DM1PD-L1 combined positive scoreTumor-infiltrating lymphocyte (TIL) statusClinical benefit rateDose-finding cohortMedian age 54Phase 2 dosePhase Ib studyCombined positive scoreAnti-PD1 antibodyPhase 1 trialDe-escalation designEligible patientsLymphocyte statusMetastatic HER2Expansion cohortOral mucositisPrimary endpointSecondary endpointsAntitumor immunityImmune signaturesPrior linesSGNLVA-001: A phase I open-label dose escalation and expansion study of SGN-LIV1A administered weekly in breast cancer.
Beckwith H, Medgyesy D, Abraham J, Nanda R, Tkaczuk K, Krop I, Pusztai L, Modi S, Mita M, Specht J, Hurvitz S, Han H, Kalinsky K, Wilks S, O'Shaughnessy J, Hart L, Rugo H, Mitri Z, Garfin P, Burris III H. SGNLVA-001: A phase I open-label dose escalation and expansion study of SGN-LIV1A administered weekly in breast cancer. Journal Of Clinical Oncology 2020, 38: tps1104-tps1104. DOI: 10.1200/jco.2020.38.15_suppl.tps1104.Peer-Reviewed Original ResearchMetastatic breast cancerMonomethyl auristatin EDose-expansion cohortsAntibody-drug conjugatesDose escalationBreast cancerRECIST v1.1Expansion cohortPrior linesCytotoxic chemotherapyMetastatic triple-negative breast cancerGrade 2 peripheral neuropathyInvestigational antibody-drug conjugateNegative metastatic breast cancerLIV-1Triple-negative breast cancerAdequate organ functionHumanized IgG1 monoclonal antibodyKey efficacy endpointsPrimary safety endpointProgression-free survivalDose-limiting toxicityDuration of responseOverall response rateMonths of completion
2019
Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Tolaney S, Barroso-Sousa R, Keenan T, Trippa L, Hu J, Luis I, Wulf G, Spring L, Sinclair N, Andrews C, Pittenger J, Richardson E, Dillon D, Lin N, Overmoyer B, Partridge A, VanAllen E, Mittendorf E, Winer E, Krop I. Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2019, 37: 1004-1004. DOI: 10.1200/jco.2019.37.15_suppl.1004.Peer-Reviewed Original ResearchProgression-free survivalObjective response rateNeutrophil-lymphocyte ratioTumor-infiltrating lymphocytesTumor mutation burdenOverall survivalPrior linesMedian progression-free survivalCheckpoint inhibitor monotherapyMedian prior linesKey secondary endpointLines of chemotherapyPD-L1 statusTime of progressionChemotherapy 1Eligible patientsHormonal therapyPrimary endpointProtocol therapySecondary endpointsInhibitor monotherapyArm BMedian ageArm ATherapy 2
2015
Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer
Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, Brock J, Larrabee K, Paweletz C, Ivanova E, Janne P, Overmoyer B, Wright JJ, Shapiro GI, Winer EP, Krop IE. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Investigational New Drugs 2015, 33: 1108-1114. PMID: 26123926, PMCID: PMC4608248, DOI: 10.1007/s10637-015-0269-8.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPhase 2 studyProgression-free survivalBreast cancerPartial responseSingle-arm phase 2 studyResults 22 patientsPhase II studyDaily oral dosingOverall response rateRecent preclinical dataMechanism of actionTivantinib monotherapyMetastatic settingAdverse eventsII studyMethods PatientsPrior linesPreclinical dataOral dosingTivantinibPatientsMET expressionResponse rate
2013
A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer
Lin NU, Seah DS, Gelman R, Desantis S, Mayer EL, Isakoff S, DiPiro P, Krop IE, Come SE, Weckstein D, Winer EP, Burstein HJ. A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2013, 139: 403-410. PMID: 23645007, DOI: 10.1007/s10549-013-2551-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerGrade 3/4 non-hematologic toxicitiesHER2-positive metastatic breast cancerNon-hematologic toxicitiesTreatment-related toxicityBreast cancerCommon treatment-related toxicitiesFirst-line patientsProtocol-based therapySecond-line cohortSecond-line patientsSecond-line settingPhase II studyProportion of patientsCombination of vinorelbineCo-primary endpointsEligible patientsFebrile neutropeniaMedian PFSII studyMedian durationObjective responsePrior linesUnacceptable toxicityMedian age