2024
A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170)
Maldonado E, Rathmell W, Shapiro G, Takebe N, Rodon J, Mahalingam D, Trikalinos N, Kalebasty A, Parikh M, Boerner S, Balido C, Krings G, Burns T, Bergsland E, Munster P, Ashworth A, LoRusso P, Aggarwal R. A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170). Cancer Research Communications 2024, 4: 1793-1801. PMID: 38920407, PMCID: PMC11264598, DOI: 10.1158/2767-9764.crc-24-0213.Peer-Reviewed Original ResearchSolid tumor malignanciesStable diseaseTumor malignancyAdverse eventsDepth of tumor responseLoss of H3K36me3Median duration of treatmentAdvanced solid tumor malignanciesClear cell renal cell carcinomaMinor tumor regressionsProlonged stable diseaseArchival tumor tissuePhase II studyCell renal cell carcinomaPhase II trialRenal cell carcinomaDuration of treatmentArchival tissue samplesSimon's two-stageTumor responseTumor regressionII trialMedian durationII studySETD2 mutationsEntinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial
Roussos Torres E, Ho W, Danilova L, Tandurella J, Leatherman J, Rafie C, Wang C, Brufsky A, LoRusso P, Chung V, Yuan Y, Downs M, O’Connor A, Shin S, Hernandez A, Engle E, Piekarz R, Streicher H, Talebi Z, Rudek M, Zhu Q, Anders R, Cimino-Mathews A, Fertig E, Jaffee E, Stearns V, Connolly R. Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial. Nature Cancer 2024, 5: 866-879. PMID: 38355777, DOI: 10.1038/s43018-024-00729-w.Peer-Reviewed Original ResearchHormone receptor-positive breast cancerReceptor-positive breast cancerTriple-negative breast cancerClinical benefit rateProgression-free survivalBreast cancerBenefit rateAdvanced HER2-negative breast cancerAdvanced triple-negative breast cancerHER2-negative breast cancerResponse rateNivolumab + ipilimumabPD-L1 statusDose-limiting toxicityPhase Ib trialTumor mutational burdenPhase II trialDose escalationExpansion cohortPD-L1II trialMutational burdenPrimary endpointSecondary endpointsMyeloid cells
2023
Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma
Fanucci K, Pilat M, Shyr D, Shyr Y, Boerner S, Li J, Durecki D, Drappatz J, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma. Cancer Research Communications 2023, 3: 192-201. PMID: 36968138, PMCID: PMC10035510, DOI: 10.1158/2767-9764.crc-22-0436.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalProlonged stable diseaseStable diseasePhase II trialGrade 4 tumorsII trialOlaparib monotherapyGrade 2Multicenter phase 2 trialSingle-arm phase II trialWorld Health Organization classificationMedian overall survivalNeuro-Oncology criteriaPhase 2 trialOverall response rateFuture patient stratificationMutant gliomasPARP inhibitor olaparibEvaluable patientsPrimary endpointOverall survivalProgressive diseaseSelect patientsClinical benefit
2022
Praluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial
Boni V, Fidler MJ, Arkenau HT, Spira A, Meric-Bernstam F, Uboha N, Sanborn RE, Sweis RF, LoRusso P, Nagasaka M, Garcia-Corbacho J, Jalal S, Harding JJ, Kim SK, Miedema IHC, Vugts DJ, Huisman MC, Zwezerijnen GJC, van Dongen GAMS, van Oordt C, Wang S, Dang T, Zein IA, Vasiljeva O, Lyman SK, Paton V, Hannah A, Liu JF. Praluzatamab Ravtansine, a CD166-Targeting Antibody–Drug Conjugate, in Patients with Advanced Solid Tumors: An Open-Label Phase I/II Trial. Clinical Cancer Research 2022, 28: 2020-2029. PMID: 35165101, PMCID: PMC9365353, DOI: 10.1158/1078-0432.ccr-21-3656.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsOpen-label phase I/II trialSolid tumorsPhase I/II trialPhase I/II clinical trialsBasis of tolerabilityPhase II doseBreast cancer subsetsAntibody-drug conjugatesProtease-cleavable linkerEligible patientsPosttreatment biopsiesPrior therapyStable diseaseII trialPartial responseSafety profileTumor regressionClinical trialsPrevalent subtypeCancer subsetsClinical activityMetastatic cancerBreast cancerMedian number
2013
A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC).
Goncalves P, Kummar S, Siu L, Hansen A, Savvides P, Sukari A, Chao J, Heilbrun L, Pilat M, Smith D, Casetta L, Boerner S, LoRusso P. A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC). Journal Of Clinical Oncology 2013, 31: 6045-6045. DOI: 10.1200/jco.2013.31.15_suppl.6045.Peer-Reviewed Original ResearchProgression-free survivalAdenoid cystic carcinomaSuberoylanilide hydroxamic acidMetastatic adenoid cystic carcinomaOverall survivalAdverse eventsResponse durationResponse rateEvaluable patientsOnly grade 3 adverse eventGrade 3 adverse eventsMedian progression-free survivalTreatment of ACCAdequate organ functionMedian overall survivalPhase II studyPhase II trialHistone deacetylasesDrug combination studiesChemo-naïveChemotherapy regimensII trialOral painSecondary endpointsThromboembolic events
2009
Population Pharmacokinetics of Trastuzumab-DM1, a First-in-Class HER2 Antibody-Drug Conjugate Given Every 3 Weeks (q3w) and Weekly (qw) to Patients with HER2-Positive Metastatic Breast Cancer (MBC).
LoRusso P, Girish S, Burris H, Beeram M, Vukelja S, Modi S, Yi J, Wang B, Saad O, Gupta M. Population Pharmacokinetics of Trastuzumab-DM1, a First-in-Class HER2 Antibody-Drug Conjugate Given Every 3 Weeks (q3w) and Weekly (qw) to Patients with HER2-Positive Metastatic Breast Cancer (MBC). Cancer Research 2009, 69: 5099-5099. DOI: 10.1158/0008-5472.sabcs-09-5099.Peer-Reviewed Original ResearchMetastatic breast cancerHER2-positive metastatic breast cancerHER2 antibody-drug conjugatesPhase II trialT-DM1Antibody-drug conjugatesII trialClinical factorsInter-individual variabilityTumor burdenIndividual patientsCovariate analysisPK parametersPK dataPK modelOngoing phase II trialSubsequent phase II trialTwo-compartment linear modelPhase I trialPopulation PK modelPopulation pharmacokinetic modelMultiple dose levelsConcentration-time dataAvailable PK dataPK parameter valuesCediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC)
Gadgeel S, Wozniak A, Edelman M, Valdivieso M, Heilbrun L, Venkatramanamoorthy R, Shields A, LoRusso P, Hackstock D, Ruckdeschel J. Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2009, 27: e19007-e19007. DOI: 10.1200/jco.2009.27.15_suppl.e19007.Peer-Reviewed Original ResearchNon-small cell lung cancerRecurrent non-small cell lung cancerFLT-PET scansNSCLC ptsDose reductionPET scansMeasurable non-small cell lung cancerConfirmed response rateDisease control ratePhase II trialMedian age 60Cell lung cancerStandard uptake valueVEGF receptor 1Males 56Pemetrexed combinationsPrior regimensBrain metastasesGrade 3/4II trialVEGF therapyMajor hemorrhageOral inhibitorControl rateLung cancer
2007
Phase I experience with c-MET inhibitor XL880 administered orally to patients (pts) with solid tumors
Eder J, Heath E, Appleman L, Shapiro G, Wang D, Malburg L, Zhu A, Leader T, Wolanski A, LoRusso P. Phase I experience with c-MET inhibitor XL880 administered orally to patients (pts) with solid tumors. Journal Of Clinical Oncology 2007, 25: 3526-3526. DOI: 10.1200/jco.2007.25.18_suppl.3526.Peer-Reviewed Original ResearchStable diseaseTumor biopsiesPhase ITreatment tumor biopsiesCommon adverse eventsECOG performance statusPhase II trialPhase 1 studyCorrelative studiesHepatocyte growth factor receptorInhibition of PDGFRβAdequate liverEvaluable ptsGrowth factor receptorII trialRECIST criteriaAdverse eventsBrain metastasesHepatic transaminasesPartial responsePerformance statusRenal functionDaily dosePlasma markersNeck cancer
2001
Multicenter, Phase II study of capecitabine in taxane‐pretreated metastatic breast carcinoma patients
Blum J, Dieras V, Russo P, Horton J, Rutman O, Buzdar A, Osterwalder B. Multicenter, Phase II study of capecitabine in taxane‐pretreated metastatic breast carcinoma patients. Cancer 2001, 92: 1759-1768. PMID: 11745247, DOI: 10.1002/1097-0142(20011001)92:7<1759::aid-cncr1691>3.0.co;2-a.Peer-Reviewed Original ResearchConceptsMetastatic breast carcinomaTreatment-related adverse eventsHand-foot syndromeBreast carcinomaAdverse eventsGrade 3 treatment-related adverse eventsCommon treatment-related adverse eventsResponse rateGrade 4 adverse eventsMetastatic breast carcinoma patientsPrevious chemotherapy regimensPrior anthracycline chemotherapyTreatment-related deathsPhase II studyPhase II trialBreast carcinoma patientsSubgroup of patientsOverall response rateCurrent multicenterFluoropyrimidine carbamateOral capecitabineAnthracycline chemotherapyChemotherapy regimensII trialTaxane therapy
1999
Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer.
Blum J, Jones S, Buzdar A, LoRusso P, Kuter I, Vogel C, Osterwalder B, Burger H, Brown C, Griffin T. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. Journal Of Clinical Oncology 1999, 17: 485-93. PMID: 10080589, DOI: 10.1200/jco.1999.17.2.485.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerTreatment-related adverse eventsHand-foot syndromeBreast cancerAdverse eventsCommon treatment-related adverse eventsLarge multicenter phase II trialOnly treatment-related adverse eventMulticenter phase II studyMulticenter phase II trialComplete response durationPrior chemotherapeutic regimensPhase II studyPhase II trialMedian survival timeFavorable toxicity profileOverall response rateFluoropyrimidine carbamateMeasurable diseaseOral capecitabineAssessable diseaseII trialII studyMedian durationMetastatic diseasePhase II study of CI-958 in colorectal cancer
Shields A, Philip P, LoRusso P, Ferris A, Zalupski M. Phase II study of CI-958 in colorectal cancer. Cancer Chemotherapy And Pharmacology 1999, 43: 162-164. PMID: 9923823, DOI: 10.1007/s002800050878.Peer-Reviewed Original ResearchConceptsAdvanced colorectal cancerColorectal cancerCI-958Patient experienced febrile neutropeniaAcute febrile reactionExperienced febrile neutropeniaPhase II studyPhase II trialStart of treatmentFebrile neutropeniaII trialMetastatic settingII studyMajor toxicityMedian survivalMetastatic diseaseObjective responseFebrile reactionsPatientsCancerDoseTreatmentLeukopeniaNeutropeniaRegimen
1998
Evaluation of pyrazoloacridine in patients with advanced pancreatic carcinoma
Zalupski M, Shields A, Philip P, Kraut M, LoRusso P, Heilbrun L, Vaitkevicius V. Evaluation of pyrazoloacridine in patients with advanced pancreatic carcinoma. Investigational New Drugs 1998, 16: 93-96. PMID: 9740550, DOI: 10.1023/a:1006087114621.Peer-Reviewed Original ResearchConceptsPancreatic carcinomaBroad preclinical antitumor activityUntreated advanced pancreatic cancerAdvanced pancreatic cancerAdvanced pancreatic carcinomaPhase II trialSchedule of administrationPreclinical antitumor activityModerate neutropeniaPredictable toxicityII trialMajor toxicityClinical efficacyMild neurotoxicityPancreatic cancerClinical developmentPatientsPyrazoloacridinePhase IAntitumor activitySolid tumor selectivityTumor selectivityCarcinomaDoseToxicity
1997
Phase II study of pyrazoloacridine in patients with advanced colorectal carcinoma
Zalupski M, Philip P, LoRusso P, Shields A. Phase II study of pyrazoloacridine in patients with advanced colorectal carcinoma. Cancer Chemotherapy And Pharmacology 1997, 40: 225-227. PMID: 9219505, DOI: 10.1007/s002800050650.Peer-Reviewed Original ResearchConceptsColorectal cancerBroad preclinical antitumor activityUntreated advanced colorectal cancerPhase II studyAdvanced colorectal cancerPhase II trialSchedule of administrationAdvanced colorectal carcinomaPreclinical antitumor activityPredictable toxicityII trialII studyClinical efficacyColorectal carcinomaClinical developmentPatientsPyrazoloacridinePhase IAntitumor activitySolid tumor selectivityTumor selectivityCancerDoseToxicityMyelosuppression
1995
Phase I clinical trial of pyrazoloacridine NSC366140 (PD115934).
LoRusso P, Foster B, Poplin E, McCormick J, Kraut M, Flaherty L, Heilbrun L, Valdivieso M, Baker L. Phase I clinical trial of pyrazoloacridine NSC366140 (PD115934). Clinical Cancer Research 1995, 1: 1487-93. PMID: 9815948.Peer-Reviewed Original ResearchConceptsGrade IV toxicityStarting doseDose escalationClinical trialsPhase I clinical trialNext dose escalationAcceptable toxicity profilePhase II trialDose-limiting toxicityPeak plasma levelsPre-clinical efficacyMultidrug-resistant tumor cellsMurine solid tumorsII trialTreatment coursePlasma levelsGrade IInterpatient variationIntermediate dosePreclinical characteristicsToxicity profilePharmacokinetic parametersDose levelsSolid tumorsTotal doseComparative efficacy of DMP 840 against mouse and human solid tumor models
LoRusso P, Demchik L, Dan M, Polin L, Gross J, Corbett T. Comparative efficacy of DMP 840 against mouse and human solid tumor models. Investigational New Drugs 1995, 13: 195-203. PMID: 8729946, DOI: 10.1007/bf00873800.Peer-Reviewed Original ResearchConceptsMouse tumorsLarger body weight lossTumor cell linesTumor modelHighest non-toxic dosePhase I clinical trialHuman tumor xenograft modelsPhase II trialDMP 840Body weight lossHuman xenograft tumorsMouse solid tumorsNorth American centersHuman solid tumor modelsPhase II testingNon-toxic doseTumor xenograft modelCell linesP388/ADRSoft agar colony formationMouse tumor modelsSolid tumor modelsAgar colony formationII trialMouse tumor cell lines