2024
Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series
Yamamoto N, Tolcher A, Hafez N, Lugowska I, Ramlau R, Macarulla T, Geng J, Li J, Teufel M, Märten A, LoRusso P. Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced Biliary Tract Cancer: A Case Series. OncoTargets And Therapy 2024, 17: 267-280. PMID: 38567193, PMCID: PMC10986405, DOI: 10.2147/ott.s440979.Peer-Reviewed Original ResearchBiliary tract cancerAdvanced biliary tract cancerAdverse eventsDose reduction due to adverse eventsBiliary tract cancer casesChemotherapy plus immunotherapyPhase Ia/Ib trialPD-1 inhibitorsSecond-line optionAnti-tumor activityStable diseasePartial responsePD-1Treatment discontinuationCase seriesSafety profilePatientsImprove outcomesMolecular heterogeneityCancerMDM2-p53DiseaseImmunotherapyDoseEfficacyPharmacokinetics (PK) of Tiragolumab in First‐in‐Human Study in Patients with Mixed Solid Tumors (GO30103)
Garralda E, Oh Y, Italiano A, Bedard P, Delord J, Calvo E, LoRusso P, Wainberg Z, Cervantes A, Rodriguez‐Vida A, Shemesh C, Sane R, Mendus D, Ding H, Hendricks R, Meng R, Cho B, Kim T, Wu B. Pharmacokinetics (PK) of Tiragolumab in First‐in‐Human Study in Patients with Mixed Solid Tumors (GO30103). The Journal Of Clinical Pharmacology 2024, 64: 544-554. PMID: 38105505, DOI: 10.1002/jcph.2397.Peer-Reviewed Original ResearchSolid tumorsMixed solid tumorsDose-proportional mannerDrug-drug interactionsSlower elimination phaseSequential dosingInter-individual variabilityIntravenous infusionSystemic exposureImmunogenicity assessmentAtezolizumabHuman studiesElimination phasePK dataPK profilesPK propertiesPatientsMonoclonal antibodiesSerum samplesPharmacokineticsDays/Multiple timepointsSingle timepointGeometric meanQ4W
2023
161TiP A phase I/II, open-label study of an anti-ILT2 (LILRB1) antibody, SAR444881, administered alone and in combination with pembrolizumab, with or without chemotherapy, or cetuximab in patients with advanced solid tumors
Perets R, Stemmer S, Geva R, Golan T, Fakih M, Cohen J, Lieu C, Jin Z, Lorusso P, Ashtamker N, Friedman I, Hakim M, Crawford N, Perez R, Agarwal M, Abbadessa G, Wu M, Lin J, Deantonio C, Borad M. 161TiP A phase I/II, open-label study of an anti-ILT2 (LILRB1) antibody, SAR444881, administered alone and in combination with pembrolizumab, with or without chemotherapy, or cetuximab in patients with advanced solid tumors. Immuno-Oncology Technology 2023, 20: 100672. DOI: 10.1016/j.iotech.2023.100672.Peer-Reviewed Original Research1101P The effect of LNS8801 in combination with pembrolizumab in patients with treatment-refractory cutaneous melanoma
Rodon J, Chaney M, Cohen J, Garyantes T, Ishizuka J, Lin J, Lorusso P, Mita A, Mita M, Muller C, Natale C, Orloff M, Papadopoulos K, Patel S, Shoushtari A. 1101P The effect of LNS8801 in combination with pembrolizumab in patients with treatment-refractory cutaneous melanoma. Annals Of Oncology 2023, 34: s663. DOI: 10.1016/j.annonc.2023.09.2235.Peer-Reviewed Original Research673P A phase I dose-escalation and expansion study evaluating the safety and efficacy of the MDM2–p53 antagonist brigimadlin (BI 907828) in patients (pts) with solid tumours
Schoeffski P, Lorusso P, Yamamoto N, Lugowska I, Garcia V, Lauer U, Hu C, Jayadeva G, Lahmar M, Gounder M. 673P A phase I dose-escalation and expansion study evaluating the safety and efficacy of the MDM2–p53 antagonist brigimadlin (BI 907828) in patients (pts) with solid tumours. Annals Of Oncology 2023, 34: s472-s473. DOI: 10.1016/j.annonc.2023.09.1859.Peer-Reviewed Original Research1029P Dazostinag (TAK-676) alone and in combination with pembrolizumab (pembro) in patients (pts) with advanced or metastatic solid tumors: Preliminary safety, PK/PD, and anti-tumor activity in a phase I dose escalation study supporting a recommended dose for expansion (RDE)
Olszanski A, Luke J, LoRusso P, Falchook G, Bedard P, Sanborn R, Patel S, Orr D, Gibbs J, Li C, Huang Y, Gregory R, Perera S, Xu R, Joshi A, Lee M, Raizer J, Gao X. 1029P Dazostinag (TAK-676) alone and in combination with pembrolizumab (pembro) in patients (pts) with advanced or metastatic solid tumors: Preliminary safety, PK/PD, and anti-tumor activity in a phase I dose escalation study supporting a recommended dose for expansion (RDE). Annals Of Oncology 2023, 34: s625-s626. DOI: 10.1016/j.annonc.2023.09.2168.Peer-Reviewed Original ResearchSingle-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Sacher A, LoRusso P, Patel M, Miller W, Garralda E, Forster M, Santoro A, Falcon A, Kim T, Paz-Ares L, Bowyer S, de Miguel M, Han S, Krebs M, Lee J, Cheng M, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Dharia N, Schutzman J, Desai J. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. New England Journal Of Medicine 2023, 389: 710-721. PMID: 37611121, DOI: 10.1056/nejmoa2303810.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalTreatment-related adverse eventsProgression-free survivalAdverse eventsSolid tumorsG12C mutationLow-grade adverse eventsGrade 3 eventsGrade 4 eventsTreatment-related deathsDiscontinuation of treatmentMetastatic solid tumorsPhase 1 studyDurable clinical responsesBiomarkers of responseKRAS G12C mutationAssessment of safetyVariant allele frequencyClinical responseColorectal cancerSerial assessmentDose reductionG12C inhibitorsPatientsTumor DNAPlatinum Sensitivity in IDH1/2 Mutated Intrahepatic Cholangiocarcinoma: Not All “BRCAness” Is Created Equal
Doroshow D, Wei W, Mehrotra M, Sia D, Eder J, Bindra R, Houldsworth J, LoRusso P, Walther Z. Platinum Sensitivity in IDH1/2 Mutated Intrahepatic Cholangiocarcinoma: Not All “BRCAness” Is Created Equal. Cancer Investigation 2023, 41: 646-655. PMID: 37505929, DOI: 10.1080/07357907.2023.2242957.Peer-Reviewed Original ResearchConceptsClinical benefit rateIntrahepatic cholangiocarcinomaPlatinum sensitivityUnresectable intrahepatic cholangiocarcinomaObjective response rateMulticenter retrospective studyHomologous recombination repairDefective homologous recombination (HR) repairPrimary endpointPlatinum chemotherapyRetrospective studyPreclinical dataBenefit rateWildtype tumorsResponse rateMT tumorsWT diseasePatientsGene defectsCholangiocarcinomaTumorsA pilot study of volumetric and density tumor analysis of ACC patients treated with vorinostat in a phase II clinical trial
Malarkey M, Toscano A, Bagheri M, Solomon J, Machado L, LoRusso P, Chen A, Folio L, Goncalves P. A pilot study of volumetric and density tumor analysis of ACC patients treated with vorinostat in a phase II clinical trial. Heliyon 2023, 9: e18680. PMID: 37593628, PMCID: PMC10428039, DOI: 10.1016/j.heliyon.2023.e18680.Peer-Reviewed Original ResearchACC patientsClinical trialsTarget lesionsSolid tumorsPhase II clinical trialPilot studyPhase 2 trialResponse Evaluation CriteriaSalivary gland cancerRare salivary gland cancerSystemic therapy efficacyStable diseaseGland cancerLung lesionsComputed tomography (CT) examsCystic carcinomaTherapy responseBlinded observersTomography examsTherapy efficacyLesionsInter-observer variationPatientsAppropriate evaluationTrialsThe MDM2–p53 antagonist BI 907828 in patients with advanced or metastatic solid tumors: results of a phase Ia, first-in-human, dose-escalation study
LoRusso P, Yamamoto N, Patel M, Laurie S, Bauer T, Geng J, Davenport T, Teufel M, Li J, Lahmar M, Gounder M. The MDM2–p53 antagonist BI 907828 in patients with advanced or metastatic solid tumors: results of a phase Ia, first-in-human, dose-escalation study. Cancer Discovery 2023, 13: 1802-1813. PMID: 37269344, PMCID: PMC10401071, DOI: 10.1158/2159-8290.cd-23-0153.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsSolid tumorsDay 1Common treatment-related adverse eventsGrowth differentiation factor-15 levelsMDM2-p53 antagonistsManageable safety profileAdvanced solid tumorsDose-escalation studyDose-limiting toxicityMetastatic solid tumorsDose-dependent increaseIA/IBAdverse eventsSafety profilePreliminary efficacyDedifferentiated liposarcomaClinical investigationCommon gradePatientsRelated commentaryIssue featureTarget engagementAntitumor activityTumors42O A phase Ia/b, dose-escalation and expansion study evaluating the MDM2–p53 antagonist BI 907828 in patients with solid tumours: Safety and efficacy in patients with dedifferentiated liposarcoma (DDLPS)
Schoeffski P, Yamamoto N, Bauer T, Patel M, Lorusso P, Lahmar M, Durland-Busbice S, Geng J, Gounder M. 42O A phase Ia/b, dose-escalation and expansion study evaluating the MDM2–p53 antagonist BI 907828 in patients with solid tumours: Safety and efficacy in patients with dedifferentiated liposarcoma (DDLPS). ESMO Open 2023, 8: 101079. DOI: 10.1016/j.esmoop.2023.101079.Peer-Reviewed Original Research
2022
759 Phase 1b study of LNS8801 in combination with pembrolizumab in patients with secondary resistance to immune checkpoint inhibitors
Rodon J, Chaney M, Cohen J, Garyantes T, Lin J, Lorusso P, Mita A, Mita M, Muller C, Natale C, Orloff M, Papadopoulos K, Patel S. 759 Phase 1b study of LNS8801 in combination with pembrolizumab in patients with secondary resistance to immune checkpoint inhibitors. 2022, a791-a791. DOI: 10.1136/jitc-2022-sitc2022.0759.Peer-Reviewed Original Research770 Safety, efficacy, and pharmacokinetic results from a phase I first-in-human study of ABBV-151 with or without anti-PD1 mAb (budigalimab) in patients with locally advanced or metastatic solid tumors
Tolcher A, Roda-Perez D, He K, Moreno V, Gomez-Roca C, Machiels J, Razak A, Sahtout M, Guan X, Jaryno-Daly S, Leibman R, Blaney M, O’Brien J, Lorusso P, Powderly J, Golan T, Miller K, Bruix J. 770 Safety, efficacy, and pharmacokinetic results from a phase I first-in-human study of ABBV-151 with or without anti-PD1 mAb (budigalimab) in patients with locally advanced or metastatic solid tumors. 2022, a801-a801. DOI: 10.1136/jitc-2022-sitc2022.0770.Peer-Reviewed Original ResearchOA03.04 Phase I A Study to Evaluate GDC-6036 Monotherapy in Patients with Non-small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation
Sacher A, Patel M, Miller W, Desai J, Garralda E, Bowyer S, Kim T, De Miguel M, Falcon A, Krebs M, Lee J, Cheng M, Han S, Shacham-Shmueli E, Forster M, Jerusalem G, Massarelli E, Rodriguez L, Prenen H, Walpole I, Arbour K, Choi Y, Dharia N, Lin M, Mandlekar S, Joo S, Shi Z, Schutzman J, LoRusso P. OA03.04 Phase I A Study to Evaluate GDC-6036 Monotherapy in Patients with Non-small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation. Journal Of Thoracic Oncology 2022, 17: s8-s9. DOI: 10.1016/j.jtho.2022.07.023.Peer-Reviewed Original Research362P Phase Ia study to evaluate GDC-6036 monotherapy in patients with colorectal cancer (CRC) with KRAS G12C mutation
Desai J, Han S, Forster M, Kim T, Casal G, Shmueli E, Bowyer S, De Miguel M, Gonzalez A, Jones R, Krebs M, Miller W, Paz-Ares L, Lorusso P, Sacher A, Dharia N, Lin M, Schutzman J, Shi Z, Patel M. 362P Phase Ia study to evaluate GDC-6036 monotherapy in patients with colorectal cancer (CRC) with KRAS G12C mutation. Annals Of Oncology 2022, 33: s701-s702. DOI: 10.1016/j.annonc.2022.07.500.Peer-Reviewed Original Research452O A phase I dose-escalation and expansion study evaluating the safety and efficacy of the MDM2–p53 antagonist BI 907828 in patients (pts) with solid tumours
Schoeffski P, Yamamoto N, Bauer T, Patel M, Gounder M, Geng J, Sailer R, Jayadeva G, Lorusso P. 452O A phase I dose-escalation and expansion study evaluating the safety and efficacy of the MDM2–p53 antagonist BI 907828 in patients (pts) with solid tumours. Annals Of Oncology 2022, 33: s743. DOI: 10.1016/j.annonc.2022.07.581.Peer-Reviewed Original Research732MO The combination of ICT01, a γ9δ2 T cell-activating mAb, plus pembrolizumab induces a broad antitumor immune response and disease control in patients with CPI-failure melanoma, NSCLC and bladder cancer: EVICTION trial
Champiat S, Wermke M, Vicier C, de Bono J, Jungels C, Vey N, Kotecki N, Wetzko K, Ruhnke L, Garralda E, de Aguiar V, Lorusso P, de Gassart A, Valentin E, Brune P, Iche M, Leparquier C, Olive D, Marabelle A, Frohna P. 732MO The combination of ICT01, a γ9δ2 T cell-activating mAb, plus pembrolizumab induces a broad antitumor immune response and disease control in patients with CPI-failure melanoma, NSCLC and bladder cancer: EVICTION trial. Annals Of Oncology 2022, 33: s877-s878. DOI: 10.1016/j.annonc.2022.07.858.Peer-Reviewed Original ResearchFirst 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
1033TiP A first-in-human phase I study of FS120, an OX40/CD137 tetravalent bispecific antibody, in patients with advanced malignancies
Papadopoulos K, Yap T, Piha-Paul S, Lorusso P, Hu-Lieskovan S, Shepherd C, Marshall S, Holz J, Poon E, Grabowska U, Kayitalire L. 1033TiP A first-in-human phase I study of FS120, an OX40/CD137 tetravalent bispecific antibody, in patients with advanced malignancies. Annals Of Oncology 2021, 32: s864-s865. DOI: 10.1016/j.annonc.2021.08.1417.Peer-Reviewed Original Research958O 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