2022
Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer
Waks AG, Keenan TE, Li T, Tayob N, Wulf GM, Richardson ET, Attaya V, Anderson L, Mittendorf EA, Overmoyer B, Winer EP, Krop IE, Agudo J, Van Allen EM, Tolaney SM. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005119. PMID: 36252998, PMCID: PMC9577940, DOI: 10.1136/jitc-2022-005119.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMetastatic breast cancerAdverse eventsBreast cancerT-DM1Immune biomarkersTrastuzumab emtansineHER2-positive metastatic breast cancerMetastatic HER2-positive breast cancerGrade 3 adverse eventsMedian progression-free survivalTreatment-related adverse eventsHuman epidermal growth factor receptor 2Cell death ligand 1HER2-positive breast cancerEpidermal growth factor receptor 2Dose-finding cohortPhase 2 dosePhase Ib studyPhase Ib trialAnti-HER2 therapyDose-limiting toxicityGrowth factor receptor 2Immune checkpoint blockade
2020
A 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 lines
2019
First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors
Garrido‐Laguna I, Krop I, Burris HA, Hamilton E, Braiteh F, Weise AM, Abu‐Khalaf M, Werner TL, Pirie‐Shepherd S, Zopf CJ, Lakshminarayanan M, Holland JS, Baffa R, Hong DS. First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors. International Journal Of Cancer 2019, 145: 1798-1808. PMID: 30680712, PMCID: PMC6875752, DOI: 10.1002/ijc.32154.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerAdvanced solid tumorsTumor responseSolid tumorsMetastatic triple-negative breast cancerPhase IPhase 2 doseAntitumor activityHuman xenograft tumor modelsAvailable standard therapiesDose-related mannerLimited antitumor activityXenograft tumor modelCommon AEsStable diseaseManageable safetyPartial responsePotent antitumor activityStandard therapyToxicity probability interval methodOvarian cancerBreast cancerPatientsRP2DTumor model
2017
Trastuzumab emtansine (T-DM1) and ribociclib, an oral inhibitor of cyclin dependent kinase 4 and 6 (CDK 4/6), for patients with metastatic HER2-positive breast cancer: Phase 1b clinical trial.
Spring L, Goel S, Juric D, Isakoff S, Haddad S, Habin K, Krop I, Moy B, Tolaney S, Bardia A. Trastuzumab emtansine (T-DM1) and ribociclib, an oral inhibitor of cyclin dependent kinase 4 and 6 (CDK 4/6), for patients with metastatic HER2-positive breast cancer: Phase 1b clinical trial. Journal Of Clinical Oncology 2017, 35: tps1106-tps1106. DOI: 10.1200/jco.2017.35.15_suppl.tps1106.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerMetastatic HER2-positive breast cancerHER2-positive breast cancerObjective response rateProgression-free survivalMetastatic breast cancerT-DM1Breast cancerTrastuzumab emtansinePhase 1b clinical trialDose-expansion cohortsMTD/RP2DPhase 2 doseDose-escalation designPre-clinical modelsInhibition of CDK4/6Cyclin-dependent kinase 4Multiple effective therapiesHER receptor familyEligible patientsRECIST 1.1Most patientsPatient ageDependent kinase 4Escalation design