2023
Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Cecchini M, Zhang J, Wei W, Sklar J, Lacy J, Zhong M, Kong Y, Zhao H, DiPalermo J, Devine L, Stein S, Kortmansky J, Johung K, Bindra R, LoRusso P, Schalper K. Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer. Cancer Research Communications 2023, 3: 1132-1139. PMID: 37387791, PMCID: PMC10305782, DOI: 10.1158/2767-9764.crc-23-0045.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMGMT protein expressionColorectal cancerStable diseaseQuantitative immunofluorescenceT cellsProtein expressionPromoter hypermethylationLow MGMT protein expressionPARP inhibitorsRadiographic tumor regressionMetastatic colorectal cancerAdvanced colorectal cancerPretreatment tumor biopsiesEffector T cellsTumor-infiltrating lymphocytesMGMT proteinDNA repair biomarkersBaseline CD8Eligible patientsIncreased CD8Methylguanine-DNA methyltransferaseObjective responseProgressive diseaseImmune markersFirst-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors
Bendell J, LoRusso P, Overman M, Noonan A, Kim D, Strickler J, Kim S, Clarke S, George T, Grimison P, Barve M, Amin M, Desai J, Wise-Draper T, Eck S, Jiang Y, Khan A, Wu Y, Martin P, Cooper Z, Elgeioushi N, Mueller N, Kumar R, Patel S. First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. Cancer Immunology, Immunotherapy 2023, 72: 2443-2458. PMID: 37016126, PMCID: PMC10264501, DOI: 10.1007/s00262-023-03430-6.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsPancreatic ductal adenocarcinomaColorectal cancerExpansion cohortHuman studiesResponse rateAnti-CD73 monoclonal antibodyProgression-free survival ratesTumor cellsMonoclonal antibodiesCommon being fatigueManageable safety profileObjective response rateAdvanced colorectal cancerAdvanced solid tumorsCell lung cancerPeripheral T cellsDate of registrationCD73 enzymatic activityAdverse eventsEscalation cohortsLocal immunosuppressionCD73 expressionSafety profileLung cancer
2021
Safety and efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab ± durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC).
Bendell J, LoRusso P, Overman M, Noonan A, Kim D, Strickler J, Kim S, Clarke S, George T, Grimison P, Barve M, Amin M, Desai J, Wise-Draper T, Cooper Z, Elgeioushi N, Mueller N, Kumar R, Wu K, Patel S. Safety and efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab ± durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC). Journal Of Clinical Oncology 2021, 39: 9047-9047. DOI: 10.1200/jco.2021.39.15_suppl.9047.Peer-Reviewed Original ResearchTreatment-related adverse eventsPancreatic ductal adenocarcinomaCommon treatment-related adverse eventsAdvanced colorectal cancerObjective responseCombination therapyColorectal cancerEGFRm NSCLCEscalation phaseNSCLC ptsEGFR-mutant non-small cell lung cancerNon-small cell lung cancerMicrosatellite stable colorectal cancerTolerable safety profileUpregulation of CD73Cell lung cancerDuration of responseStable colorectal cancerRECIST v1.1Expansion cohortPrevious interim analysisClinical responseData cutoffLocal immunosuppressionManageable safety
2018
Safety, efficacy and pharmacodynamics (PD) of MEDI9447 (oleclumab) alone or in combination with durvalumab in advanced colorectal cancer (CRC) or pancreatic cancer (panc).
Overman M, LoRusso P, Strickler J, Patel S, Clarke S, Noonan A, Prasanna T, Amin M, Nemunaitis J, Desai J, O'Byrne K, George T, Englert J, She D, Cooper Z, Wu Y, Khan A, Kumar R, Bendell J. Safety, efficacy and pharmacodynamics (PD) of MEDI9447 (oleclumab) alone or in combination with durvalumab in advanced colorectal cancer (CRC) or pancreatic cancer (panc). Journal Of Clinical Oncology 2018, 36: 4123-4123. DOI: 10.1200/jco.2018.36.15_suppl.4123.Peer-Reviewed Original Research
2017
Dose escalation results from a first-in-human, phase 1 study of the glucocorticoid-induced TNF receptor-related protein (GITR) agonist AMG 228 in patients (Pts) with advanced solid tumors.
Tran B, Carvajal R, Marabelle A, Patel S, LoRusso P, Rasmussen E, Juan G, Upreti V, Ngarmchamnanrith G, Schöffski P. Dose escalation results from a first-in-human, phase 1 study of the glucocorticoid-induced TNF receptor-related protein (GITR) agonist AMG 228 in patients (Pts) with advanced solid tumors. Journal Of Clinical Oncology 2017, 35: 2521-2521. DOI: 10.1200/jco.2017.35.15_suppl.2521.Peer-Reviewed Original ResearchGlucocorticoid-induced TNF receptor-related proteinAdvanced solid tumorsDose-limiting toxicityPhase 1 studyAdverse eventsSolid tumorsObjective responseDose escalationCell carcinomaNon-small cell lung cancerRefractory advanced colorectal cancerTreatment-emergent adverse eventsHuman IgG1 monoclonal antibodyPhase 2 doseUrothelial transitional cell carcinomaAdvanced colorectal cancerRegulatory T cellsCell lung cancerSquamous cell carcinomaTransitional cell carcinomaDose-escalation resultsT cell activationReceptor-related proteinPopulation of ptsIgG1 monoclonal antibody
1999
Phase 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
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
1994
Randomized clinical trial of mitomycin-C with or without pretreatment with WR-2721 in patients with advanced colorectal cancer
Poplin E, LoRusso P, Lokich J, Gullo J, Leming P, Schulz J, Veach S, McCulloch W, Baker L, Schein P. Randomized clinical trial of mitomycin-C with or without pretreatment with WR-2721 in patients with advanced colorectal cancer. Cancer Chemotherapy And Pharmacology 1994, 33: 415-419. PMID: 8306416, DOI: 10.1007/bf00686271.Peer-Reviewed Original ResearchConceptsColorectal cancerMyelosuppressive potentialRefractory colorectal cancerMetastatic colorectal cancerAdvanced colorectal cancerRandomized clinical trialsUse of mitomycinRefractory colorectal carcinomaMitomycin therapyPlatelet nadirsHematologic toxicityPrincipal toxicityPartial responseClinical trialsColorectal carcinomaSame dosePatientsMitomycinCancerThrombocytopeniaTherapyToxicityGroupPretreatmentFluorouracil