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 markers
2022
First in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response
Yap TA, Gainor JF, Callahan MK, Falchook GS, Pachynski RK, LoRusso P, Kummar S, Gibney GT, Burris HA, Tykodi SS, Rahma OE, Seiwert TY, Papadopoulos KP, Murphy M, Park H, Hanson A, Hashambhoy-Ramsay Y, McGrath L, Hooper E, Xiao X, Cohen H, Fan M, Felitsky D, Hart C, McComb R, Brown K, Sepahi A, Jimenez J, Zhang W, Baeck J, Laken H, Murray R, Trehu E, Harvey CJ. First in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response. Clinical Cancer Research 2022, 28: 3695-3708. PMID: 35511938, PMCID: PMC9433959, DOI: 10.1158/1078-0432.ccr-21-4256.Peer-Reviewed Original ResearchConceptsSubset of patientsPredictive biomarkersPharmacodynamic biomarkersModest objective response rateNon-small cell lung cancer trialsCD4 T cell populationCell lung cancer trialsPhase IObjective response ratePhase II doseAdvanced solid tumorsCD4 T cellsFavorable safety profilePotential predictive biomarkersLung cancer trialsPredictors of responseT cell populationsGreater clinical benefitClinical outcomesClinical benefitSafety profileCancer trialsNivolumabT cellsPatients
2021
503 Clinical activity of ICT01, an anti-BTN3A-targeted, γ9δ2-activating mAb, alone and in combination with pembrolizumab in patients with advanced/refractory solid tumors: EVICTION trial
Wermke M, Marabelle A, Jungels C, Bono J, Vey N, Vicier C, Garralda E, Gouill S, LoRusso P, Champiat S, List C, Aguiar V, Wetzko K, Rhunke L, Gassart A, Brune P, Valentin E, Iche M, Olive D, Frohna P. 503 Clinical activity of ICT01, an anti-BTN3A-targeted, γ9δ2-activating mAb, alone and in combination with pembrolizumab in patients with advanced/refractory solid tumors: EVICTION trial. 2021, a535-a535. DOI: 10.1136/jitc-2021-sitc2021.503.Peer-Reviewed Original ResearchΓ9δ2 T cellsCD8 T cellsRefractory solid tumorsSolid tumor patientsT cellsSolid tumorsTumor patientsBroad antitumor immune responseHospital Universitari Vall d’HebronEthics CommitteeT-cell countsAntitumor immune responseTumor-infiltrating lymphocytesNK cell activationPreliminary efficacy dataInstitut Jules BordetDose-dependent increaseSubsequent clinical benefitCytokine level analysisCommon AEsDose cohortsEudraCT numberLow TILsPhase 1/2aSerum cytokines958O Coordinated activation of antitumor responses of g9d2 and CD8 T-cells by targeting BTN3A with ICT01 in patients with solid tumors: EVICTION trial
Marabelle A, Wermke M, Jungels C, de Bono J, Vey N, Garralda E, Lorusso P, Olive D, Frohna P. 958O Coordinated activation of antitumor responses of g9d2 and CD8 T-cells by targeting BTN3A with ICT01 in patients with solid tumors: EVICTION trial. Annals Of Oncology 2021, 32: s829-s830. DOI: 10.1016/j.annonc.2021.08.1343.Peer-Reviewed Original Research
2020
412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors
Garralda E, Geva R, Ben-Ami E, Maurice-Dror C, Calvo E, LoRusso P, Türeci Ö, Niewood M, Şahin U, Jure-Kunkel M, Forssmann U, Ahmadi T, Melero I. 412 First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors. Journal For ImmunoTherapy Of Cancer 2020, 8: a250-a251. DOI: 10.1136/jitc-2020-sitc2020.0412.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-limiting toxicityPhase I/IIa trialTransaminase elevationAdverse eventsSolid tumorsIIa trialClinical activityT cellsDose levelsGrade 3 transaminase elevationTreatment-related adverse eventsEffector memory T cellsSerum interferon-gamma levelTriple-negative breast cancerInitial clinical activityAntitumor activityImmune checkpoint inhibitorsManageable safety profilePD-L1 axisInterferon-gamma levelsMemory T cellsEarly clinical activityEnd of infusionNarrow therapeutic windowPhase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer.
Powderly J, Chmielowski B, Brahmer J, Piha-Paul S, Bowyer S, LoRusso P, Catenacci D, Wu C, Barve M, Chisamore M, Nasrah N, Johnson D, Ho W. Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer. Journal Of Clinical Oncology 2020, 38: tps3163-tps3163. DOI: 10.1200/jco.2020.38.15_suppl.tps3163.Peer-Reviewed Original ResearchCheckpoint inhibitorsExpansion cohortT cellsPhase 1 dose escalationAnti-tumor immune responseTumor microenvironmentPhase I/IIPreliminary anti-tumor activityCohort expansion phaseCohort expansion studyPhase 2 dosePredominant chemokine receptorPhase 1/2 studyDose-escalation phaseEffector T cellsRegulatory T cellsAnti-tumor responseTumor-associated macrophagesAnti-tumor efficacyAnti-tumor activityEligible subjectsDendritic cellsDose escalationPhase 1/2Advanced cancerAssociation of an RNA signature (RS) with emergence of ICOS hi CD4 T cells and efficacy outcomes for the ICOS agonist vopratelimab (vopra) and nivolumab (nivo) in patients (pts) on the ICONIC trial.
Yap T, Gainor J, Burris H, Kummar S, Pachynski R, Callahan M, LoRusso P, Tykodi S, Gibney G, Falchook G, Rahma O, Seiwert T, Papadopoulos K, Mier J, Hashambhoy-Ramsay Y, Felitsky D, Lee D, McGrath L, Harvey C, Hooper E. Association of an RNA signature (RS) with emergence of ICOS hi CD4 T cells and efficacy outcomes for the ICOS agonist vopratelimab (vopra) and nivolumab (nivo) in patients (pts) on the ICONIC trial. Journal Of Clinical Oncology 2020, 38: 14-14. DOI: 10.1200/jco.2020.38.5_suppl.14.Peer-Reviewed Original ResearchCD4 T cellsCD4 T effector cellsT effector cellsT cellsRNA signatureRECIST responseClinical outcomesEffector cellsTumor biopsiesPre-treatment tumor biopsiesCD4 T cell populationBaseline tumor biopsiesPD-L1 TPSPD-1 inhibitorsAdvanced solid tumorsRetrospective subset analysisImmune cell infiltrationPotential predictive biomarkersT cell populationsPD-L1 IHCActivated T cellsBaseline tumorEfficacy outcomesPD-L1Combo therapy
2019
Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors
Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clinical Cancer Research 2019, 25: 3220-3228. PMID: 30770348, PMCID: PMC7980952, DOI: 10.1158/1078-0432.ccr-18-2740.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorHumansImidazolesIndoleamine-Pyrrole 2,3,-DioxygenaseIndolesMagnetic Resonance ImagingMiddle AgedNeoplasm MetastasisNeoplasm StagingNeoplasmsTomography, X-Ray ComputedTreatment OutcomeConceptsPD-L1 inhibitorsT cellsPartial responseAdvanced cancerDay 1Dose levelsCommon treatment-related AEsDose-escalation stageTreatment-related AEsAdvanced solid tumorsEffector T cellsRegulatory T cellsLinear pharmacokinetic profileLocal tumor microenvironmentInvestigational small-molecule inhibitorExpansion patientsKynurenine accumulationComplete responseImmune suppressionIntravenous infusionAcceptable safetyTryptophan depletionNavoximodAtezolizumabPlasma Kyn
2013
Clinical and pharmacodynamic (PD) results of a phase I trial with AMP-224 (B7-DC Fc) that binds to the PD-1 receptor.
Infante J, Powderly J, Burris H, Kittaneh M, Grice J, Smothers J, Brett S, Fleming M, May R, Marshall S, Devenport M, Pillemer S, Pardoll D, Chen L, Langermann S, LoRusso P. Clinical and pharmacodynamic (PD) results of a phase I trial with AMP-224 (B7-DC Fc) that binds to the PD-1 receptor. Journal Of Clinical Oncology 2013, 31: 3044-3044. DOI: 10.1200/jco.2013.31.15_suppl.3044.Peer-Reviewed Original ResearchPD-1B7-H1T cellsFunctional T cell responsesT cell effector functionPK/PD relationshipInflammatory adverse eventsPD-1 axisAdvanced solid tumorsPre-treatment biopsiesTumor immune evasionPhase I trialT cell poolT cell responsesInitial disease progressionPD-1 receptorCell effector functionsFunctional T cellsMultiple tumor typesBaseline tumorPD-1highStable diseaseB7-DCLymphocyte subsetsAdverse events