2022
BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair
Jimenez-Sainz J, Mathew J, Moore G, Lahiri S, Garbarino J, Eder JP, Rothenberg E, Jensen RB. BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair. ELife 2022, 11: e79183. PMID: 36098506, PMCID: PMC9545528, DOI: 10.7554/elife.79183.Peer-Reviewed Original ResearchConceptsHomology-directed repairDNA double-strand breaksFork protectionReplication fork protectionRad51 nucleoprotein filamentsMissense mutationsSingle amino acid substitutionRad51-ssDNA complexesDouble-strand breaksUnknown functional consequencesBRCA2 VUSAmino acid substitutionsGenome stabilityNucleoprotein filamentDNA repairRepeat regionSpacer regionBRCA2 proteinBenign allelesCellular responsesAcid substitutionsFunctional consequencesFrameshift mutationGene predisposeBRC2Correction: A Phase I Study of an MPS1 Inhibitor (BAY 1217389) in Combination with Paclitaxel Using a Novel Randomized Continual Reassessment Method for Dose Escalation
Atrafi F, Boix O, Subbiah V, Diamond JR, Chawla SP, Tolcher AW, LoRusso PM, Eder JP, Gutierrez M, Sankhala K, Rajagopalan P, Genvresse I, Langer S, Mathijssen RHJ, Verweij J, Bruns I, Lolkema MP. Correction: A Phase I Study of an MPS1 Inhibitor (BAY 1217389) in Combination with Paclitaxel Using a Novel Randomized Continual Reassessment Method for Dose Escalation. Clinical Cancer Research 2022, 28: 2969-2969. PMID: 35775194, DOI: 10.1158/1078-0432.ccr-22-1792.Peer-Reviewed Original ResearchReply to E. Rosenbaum et al
Eder JP. Reply to E. Rosenbaum et al. JCO Precision Oncology 2022, 6: e2200136. PMID: 35675573, PMCID: PMC9200392, DOI: 10.1200/po.22.00136.Peer-Reviewed Original ResearchAnti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade
Gomez-Roca C, Cassier P, Zamarin D, Machiels JP, Gracia J, Hodi F, Taus A, Garcia M, Boni V, Eder JP, Hafez N, Sullivan R, Mcdermott D, Champiat S, Aspeslagh S, Terret C, Jegg AM, Jacob W, Cannarile MA, Ries C, Korski K, Michielin F, Christen R, Babitzki G, Watson C, Meneses-Lorente G, Weisser M, Rüttinger D, Delord JP, Marabelle A. Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade. Journal For ImmunoTherapy Of Cancer 2022, 10: e004076. PMID: 35577503, PMCID: PMC9114963, DOI: 10.1136/jitc-2021-004076.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerUrothelial bladder cancerObjective response rateOptimal biological doseImmune checkpoint blockersUBC patientsConfirmed objective response rateTreatment-related adverse eventsCell death 1 ligandPhase 1b studyManageable safety profileImmune checkpoint blockadeCell lung cancerDeath 1 ligandAtezolizumab monotherapyPatients naïveAdverse eventsCheckpoint blockadeCheckpoint blockersNSCLC patientsSkin rashDose escalationClinical benefitSafety profileLung cancerYale Precision Medicine Tumor Board: reawakening the guardian of the genome
Grant MJ, Finberg KE, Walther Z, Stein SM, Lacy J, Eder JP, Goldberg SB. Yale Precision Medicine Tumor Board: reawakening the guardian of the genome. The Lancet Oncology 2022, 23: 337-338. PMID: 35240081, DOI: 10.1016/s1470-2045(22)00037-7.Peer-Reviewed Case Reports and Technical NotesInfluence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma
Haddad RI, Seiwert TY, Chow LQM, Gupta S, Weiss J, Gluck I, Eder JP, Burtness B, Tahara M, Keam B, Kang H, Muro K, Albright A, Mogg R, Ayers M, Huang L, Lunceford J, Cristescu R, Cheng J, Mehra R. Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma. Journal For ImmunoTherapy Of Cancer 2022, 10: e003026. PMID: 35217573, PMCID: PMC8883256, DOI: 10.1136/jitc-2021-003026.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaSquamous cell carcinomaPD-L1P16 immunohistochemistryCell carcinomaAnti-programmed death-1 therapyRecurrent/metastatic headInflammatory gene expression profileTumor human papillomavirus (HPV) statusPD-L1 CPSHuman papillomavirus (HPV) statusPD-L1 expressionRandomized clinical trialsTumor mutational burdenPretreatment tumor samplesWhole-exome sequencingM HNSCCMetastatic headClinical responseHPV resultsHPV statusInflammatory biomarkersObjective responseClinical outcomesClinical trials
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 studiesPhase 1 Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844)
Roussos Torres ET, Rafie C, Wang C, Lim D, Brufsky A, LoRusso P, Eder JP, Chung V, Downs M, Geare M, Piekarz R, Streicher H, Anforth L, Rudek MA, Zhu Q, Besharati S, Cimino-Mathews A, Anders RA, Stearns V, Jaffee EM, Connolly RM. Phase 1 Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844). Clinical Cancer Research 2021, 27: clincanres.5017.2021. PMID: 34135021, PMCID: PMC8563383, DOI: 10.1158/1078-0432.ccr-20-5017.Peer-Reviewed Original ResearchConceptsCD8/FOXP3 ratioAdvanced solid tumorsAdverse eventsAddition of ICIFOXP3 ratioSolid tumorsGrade 3/4 adverse eventsRegulatory T cell ratioTreatment-related adverse eventsImmune checkpoint inhibitor efficacyTriple-negative breast cancerMulticenter phase I clinical trialPhase I clinical trialObjective response ratePhase II doseT cell ratioCheckpoint inhibitor efficacyPhase 1 studyCombination of entinostatHistone deacetylase inhibitor entinostatRECIST 1.1Primary endpointSecondary endpointsComplete responseDose escalationIdentifying 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 selectionMelanomaYale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan
Gibson JA, Finberg KE, Nalbantoglu I, Cecchini M, Ganzak A, Walther Z, Sklar JL, Eder JP, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan. The Lancet Oncology 2021, 22: 306-307. PMID: 33662283, DOI: 10.1016/s1470-2045(20)30683-5.Peer-Reviewed Case Reports and Technical NotesClinical 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 parametersSkin puckering and edema during durvalumab therapy
Olamiju B, Odell I, Panse G, Eder JP, Leventhal JS. Skin puckering and edema during durvalumab therapy. JAAD Case Reports 2020, 7: 110-112. PMID: 33364282, PMCID: PMC7750709, DOI: 10.1016/j.jdcr.2020.11.019.Peer-Reviewed Original Research
2019
Tissue/Site-Agnostic Study of Ribociclib for Tumors With Cyclin D-CDK4/6 Pathway Genomic Alterations: A Phase II, Open-Label, Single-Arm Basket Study.
Peguero J, Sohal DPS, O'Neil BH, Safran H, Kelly K, Grilley-Olson JE, Subbiah V, Nadauld L, Purkayastha D, Stealey E, Ricart AD, Kang BP, Eder JP. Tissue/Site-Agnostic Study of Ribociclib for Tumors With Cyclin D-CDK4/6 Pathway Genomic Alterations: A Phase II, Open-Label, Single-Arm Basket Study. JCO Precision Oncology 2019, 3: 1-10. PMID: 35100715, DOI: 10.1200/PO.18.00383.Peer-Reviewed Original Research
2014
New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs
Jürgensmeier JM, Eder JP, Herbst RS. New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs. Clinical Cancer Research 2014, 20: 4425-4435. PMID: 25183480, PMCID: PMC5369358, DOI: 10.1158/1078-0432.ccr-13-0753.Peer-Reviewed Original ResearchConceptsClinical trialsTumor biologyFuture patient selectionTherapy of patientsOngoing clinical evaluationBroad molecular profilingPromising tumor targetPersonalized medicinePatient selectionPatient populationTreatment recommendationsClinical evaluationTumor boardClinical studiesImmune parametersNovel agentsTumor targetsTreatment approachesSolid tumorsClinical researchPatientsMolecular profilingSpecific markersTumorsTrials
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 activityA phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours.
Penson RT, Seiden MV, Matulonis UA, Appleman LJ, Fuller AF, Goodman A, Campos SM, Clark JW, Roche M, Eder JP. A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours. British Journal Of Cancer 2005, 93: 54-9. PMID: 15986034, PMCID: PMC2361482, DOI: 10.1038/sj.bjc.6602671.Peer-Reviewed Original Research
2001
Phase I clinical trial of 7-cyanoquinocarcinol (DX-52-1) in adult patients with refractory solid malignancies.
Bunnell CA, Supko JG, Eder JP, Clark JW, Lynch TJ, Kufe DW, Shulman LN. Phase I clinical trial of 7-cyanoquinocarcinol (DX-52-1) in adult patients with refractory solid malignancies. Cancer Chemotherapy And Pharmacology 2001, 48: 347-55. PMID: 11761451, DOI: 10.1007/s002800100319.Peer-Reviewed Original ResearchPhase I and pharmacokinetic study of LU79553, a DNA intercalating bisnaphthalimide, in patients with solid malignancies.
Villalona-Calero MA, Eder JP, Toppmeyer DL, Allen LF, Fram R, Velagapudi R, Myers M, Amato A, Kagen-Hallet K, Razvillas B, Kufe DW, Von Hoff DD, Rowinsky EK. Phase I and pharmacokinetic study of LU79553, a DNA intercalating bisnaphthalimide, in patients with solid malignancies. Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology 2001, 19: 857-69. PMID: 11157040, DOI: 10.1200/JCO.2001.19.3.857.Peer-Reviewed Original ResearchPhase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies.
Ryan DP, Supko JG, Eder JP, Seiden MV, Demetri G, Lynch TJ, Fischman AJ, Davis J, Jimeno J, Clark JW. Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies. Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research 2001, 7: 231-42. PMID: 11234874.Peer-Reviewed Original Research