2021
Ceralasertib-Mediated ATR Inhibition Combined With Olaparib in Advanced Cancers Harboring DNA Damage Response and Repair Alterations (Olaparib Combinations)
Mahdi H, Hafez N, Doroshow D, Sohal D, Keedy V, T. K, LoRusso P, Jürgensmeier J, Avedissian M, Sklar J, Glover C, Felicetti B, Dean E, Mortimer P, Shapiro GI, Eder JP. Ceralasertib-Mediated ATR Inhibition Combined With Olaparib in Advanced Cancers Harboring DNA Damage Response and Repair Alterations (Olaparib Combinations). JCO Precision Oncology 2021, 5: 1432-1442. PMID: 34527850, PMCID: PMC8437220, DOI: 10.1200/po.20.00439.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian cancerComplete responseResponse rateClinical benefit ratePartial response ratePrimary end pointOverall response rateHomologous recombination repair deficiencySerous ovarian cancerPoly (ADP-ribose) polymerase (PARP) inhibitorsPrior therapyUnacceptable toxicityEntire cohortRefractory cancerBenefit rateOvarian cancerPromising therapyPatientsBasket trialsDay 1End pointOlaparibPolymerase inhibitorsTherapyAdditional studiesIdentifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial
LoRusso PM, Sekulic A, Sosman JA, Liang WS, Carpten J, Craig DW, Solit DB, Bryce AH, Kiefer JA, Aldrich J, Nasser S, Halperin R, Byron SA, Pilat MJ, Boerner SA, Durecki D, Hendricks WPD, Enriquez D, Izatt T, Keats J, Legendre C, Markovic SN, Weise A, Naveed F, Schmidt J, Basu GD, Sekar S, Adkins J, Tassone E, Sivaprakasam K, Zismann V, Calvert VS, Petricoin EF, Fecher LA, Lao C, Eder JP, Vogelzang NJ, Perlmutter J, Gorman M, Manica B, Fox L, Schork N, Zelterman D, DeVeaux M, Joseph RW, Cowey CL, Trent JM. Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial. PLOS ONE 2021, 16: e0248097. PMID: 33826614, PMCID: PMC8026051, DOI: 10.1371/journal.pone.0248097.Peer-Reviewed Original ResearchConceptsMetastatic melanomaAlternate treatment armResponse-evaluable patientsMetastatic melanoma patientsComprehensive genomic profilingAdditional drug classesCutaneous metastatic melanomaLack of responseCombination BRAFStable diseaseTwo-stage optimal designPartial responseProgressive diseaseCare therapyMelanoma patientsMelanoma TrialTreatment armsTreatment optionsBRAFV600 mutationsClinical trialsDrug classesResponse ratePatientsDrug selectionMelanomaClinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas
Eder JP, Doroshow DB, T. K, Keedy VL, Sklar JS, Glazer P, Bindra R, Shapiro GI. Clinical Efficacy of Olaparib in IDH1/IDH2-Mutant Mesenchymal Sarcomas. JCO Precision Oncology 2021, 5: 466-472. PMID: 34994649, PMCID: PMC9848565, DOI: 10.1200/po.20.00247.Peer-Reviewed Original ResearchConceptsPulmonary epithelioid hemangioendotheliomaStable diseaseEpithelioid hemangioendotheliomaClinical benefitClinical benefit rateOpen-label studyPrimary end pointPoly (ADP-ribose) polymerase inhibitionDefective homologous recombination (HR) repairMesenchymal sarcomaObjective responsePartial responseClinical efficacyPatient populationBenefit rateCombination trialsPatientsSolid tumorsIDH1/2-mutant tumorsIDH1/2 mutationsPARP inhibitorsEnd pointPARP inhibitionTumorsOlaparib
2020
A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma
Shapiro GI, LoRusso P, Dowlati A, T. Do K, Jacobson CA, Vaishampayan U, Weise A, Caimi PF, Eder JP, French CA, Labriola-Tompkins E, Boisserie F, Pierceall WE, Zhi J, Passe S, DeMario M, Kornacker M, Armand P. A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma. British Journal Of Cancer 2020, 124: 744-753. PMID: 33311588, PMCID: PMC7884382, DOI: 10.1038/s41416-020-01180-1.Peer-Reviewed Original ResearchConceptsLarge B-cell lymphomaPhase 1 studyB-cell lymphomaSolid tumorsCommon treatment-related adverse eventsTreatment-related adverse eventsPeripheral blood mononuclear cellsInjection site erythemaObjective response rateSingle-agent activityBlood mononuclear cellsExtra-terminal (BET) protein inhibitorsSmall-molecule BET inhibitorsConclusionsThis trialAdverse eventsPharmacodynamic assessmentMononuclear cellsNUT carcinomaCD11b levelsExtra-terminal (BET) proteinsClinical trialsTestis carcinomaSustained decreaseFavorable pharmacokineticsPharmacokinetic parameters
2005
Proteasome Inhibition With Bortezomib (PS-341): A Phase I Study With Pharmacodynamic End Points Using a Day 1 and Day 4 Schedule in a 14-Day Cycle
Hamilton AL, Eder JP, Pavlick AC, Clark JW, Liebes L, Garcia-Carbonero R, Chachoua A, Ryan DP, Soma V, Farrell K, Kinchla N, Boyden J, Yee H, Zeleniuch-Jacquotte A, Wright J, Elliott P, Adams J, Muggia FM. Proteasome Inhibition With Bortezomib (PS-341): A Phase I Study With Pharmacodynamic End Points Using a Day 1 and Day 4 Schedule in a 14-Day Cycle. Journal Of Clinical Oncology 2005, 23: 6107-6116. PMID: 16135477, DOI: 10.1200/jco.2005.01.136.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityDay 1Main dose-limiting toxicityPhase IGrade 3 thrombocytopeniaPhase II doseCell lung cancerPharmacodynamic end pointsRenal cell carcinomaProteasome activityNovel antineoplastic agentPartial responseCell carcinomaLung cancerToxicity profileWeek scheduleAntitumor effectsDose levelsPatientsSolid tumorsTotal doseHigh dosesTotal dosesNeurotoxic agentsBaseline activity