2024
Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer.
Jhaveri K, Accordino M, Bedard P, Cervantes A, Gambardella V, Hamilton E, Italiano A, Kalinsky K, Krop I, Oliveira M, Schmid P, Saura C, Turner N, Varga A, Cheeti S, Hilz S, Hutchinson K, Jin Y, Royer-Joo S, Peters U, Shankar N, Schutzman J, Juric D. Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer. Journal Of Clinical Oncology 2024, 42: 3947-3956. PMID: 39236276, DOI: 10.1200/jco.24.00110.Peer-Reviewed Original ResearchTreatment-related adverse eventsDrug-drug interactionsPreliminary antitumor activityEndocrine therapyStudy treatmentHuman epidermal growth factor receptor 2-negativeBreast cancerTreatment-related adverse event ratesLack of drug-drug interactionsConfirmed objective response rateLocally advanced/metastatic breast cancerCirculating tumor DNA analysisEffect of study treatmentPK drug-drug interactionsAntitumor activityObjective response ratePhase I/Ib studyHormone receptor-positiveProgression-free survivalAdvanced/metastatic breast cancerTumor DNA analysisBiomarkers of responseMetastatic breast cancerYears of ageReceptor-positive
2022
Long-term safety of inavolisib (GDC-0077) in an ongoing phase 1/1b study evaluating monotherapy and in combination (combo) with palbociclib and/or endocrine therapy in patients (pts) with PIK3CA-mutated, hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (BC).
Bedard P, Accordino M, Cervantes A, Gambardella V, Hamilton E, Italiano A, Juric D, Kalinsky K, Krop I, Oliveira M, Saura C, Schmid P, Turner N, Varga A, Shankar N, Schutzman J, Royer-Joo S, Martin M, Jhaveri K. Long-term safety of inavolisib (GDC-0077) in an ongoing phase 1/1b study evaluating monotherapy and in combination (combo) with palbociclib and/or endocrine therapy in patients (pts) with PIK3CA-mutated, hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (BC). Journal Of Clinical Oncology 2022, 40: 1052-1052. DOI: 10.1200/jco.2022.40.16_suppl.1052.Peer-Reviewed Original ResearchBreast cancerPO QDHormone receptor-positive/HER2-negative metastatic breast cancerFrequent treatment-related adverse eventsFrequent treatment-related grade 3HER2-negative metastatic breast cancerTreatment-related adverse eventsTreatment-related grade 3G3-4 neutropeniaPhase 1/1b studyPhase 3 doseLong-term tolerabilityNew safety signalsOverall study populationPhase 3 studyMetastatic breast cancerPreliminary antitumor activityLong-term safetyFemale ptsEndocrine therapyPrior therapyDose intensityAdverse eventsArm BMedian age
2020
Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study
Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study. Journal Of Clinical Oncology 2020, 38: 1887-1896. PMID: 32058843, PMCID: PMC7280051, DOI: 10.1200/jco.19.02318.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseHER2-low breast cancerT-DXdBreast cancerTrastuzumab deruxtecanAntitumor activityConfirmed objective response rateTopoisomerase I inhibitor payloadTreatment-emergent adverse eventsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Breast cancer refractoryIndependent adjudication committeeObjective response ratePhase Ib studyAdvanced breast cancerGrowth factor receptor 2Preliminary antitumor activityIndependent central reviewWithdrawal of consentFactor receptor 2Cancer refractoryEligible patientsMetastatic HER2Unacceptable toxicity
2018
Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial
Borges VF, Ferrario C, Aucoin N, Falkson C, Khan Q, Krop I, Welch S, Conlin A, Chaves J, Bedard PL, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. JAMA Oncology 2018, 4: 1214-1220. PMID: 29955792, PMCID: PMC6143009, DOI: 10.1001/jamaoncol.2018.1812.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveBreast NeoplasmsDiarrheaDrug Administration ScheduleFatigueFemaleHumansKaplan-Meier EstimateMaytansineMiddle AgedNauseaNeoplasm MetastasisProtein Kinase InhibitorsReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsTrastuzumabConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdo-trastuzumab emtansineT-DM1Breast cancerTyrosine kinase inhibitorsBrain metastasesAdverse eventsClinical trialsToxic reactionsDose-limiting toxic reactionHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Phase 1b clinical trialGrowth factor receptor 2ERBB2/HER2-positive breast cancerPreliminary antitumor activityTreatment of patientsSpecific tyrosine kinase inhibitorYears of ageDrug-drug interactionsFactor receptor 2Hepatic transaminitisHER2 therapy
2015
SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer
Gonzalez-Angulo AM, Krop I, Akcakanat A, Chen H, Liu S, Li Y, Culotta KS, Tarco E, Piha-Paul S, Moulder-Thompson S, Velez-Bravo V, Sahin AA, Doyle LA, Do KA, Winer EP, Mills GB, Kurzrock R, Meric-Bernstam F. SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer. Journal Of The National Cancer Institute 2015, 107: dju493. PMID: 25688104, PMCID: PMC4342675, DOI: 10.1093/jnci/dju493.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug Administration ScheduleDrug EruptionsFatigueFemaleHeterocyclic Compounds, 3-RingHumansHyperglycemiaMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNeutropeniaPaclitaxelSeverity of Illness IndexTreatment OutcomeConceptsDose escalationDay 1Day 2Higher adverse eventsPhase Ib studyWeeks of therapyAdvanced solid tumorsCTCAE grade 3Metastatic breast cancerPrevious phase IPreliminary antitumor activityDose expansionStable diseaseObjective responseUnacceptable toxicityAdverse eventsMedian ageWeekly dosesClinical benefitPharmacodynamic markersSystemic exposureExcessive toxicityTumor responseGrade 3Median number
2012
Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors
Markman B, Tabernero J, Krop I, Shapiro G, Siu L, Chen L, Mita M, Cuero M, Stutvoet S, Birle D, Anak Ö, Hackl W, Baselga J. Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors. Annals Of Oncology 2012, 23: 2399-2408. PMID: 22357447, DOI: 10.1093/annonc/mds011.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsBreast NeoplasmsColonic NeoplasmsDiarrheaFemaleFluorodeoxyglucose F18HumansImidazolesMaleMaximum Tolerated DoseMiddle AgedNauseaPhosphoinositide-3 Kinase InhibitorsProstatic NeoplasmsQuinolinesRadionuclide ImagingRadiopharmaceuticalsTOR Serine-Threonine KinasesTreatment OutcomeYoung AdultConceptsAdvanced solid tumorsPreliminary antitumor activityStable diseaseSystemic exposureAdaptive Bayesian logistic regression modelSolid tumorsPhase I dose-escalation studyI dose-escalation studyFluorodeoxyglucose positron emission tomographyStable metabolic diseaseVariable systemic exposureAntitumor activityDose-escalation studyLow systemic exposurePI3K pathway inhibitionDay three timesLogistic regression modelsAdverse eventsDose escalationFluorodeoxyglucose uptakeRapamycin inhibitorsTumor shrinkagePharmacodynamic studiesComputed tomographyMTOR inhibitors