2023
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)
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 DNAThe 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 activityTumorsCBX-12-101: A first-in-human study of CBX-12, an alphalex peptide drug conjugate (PDC) in patients (pts) with advanced or metastatic solid tumors.
Rodriguez Rivera I, Hafez N, Tolcher A, LoRusso P, Wilks S, Tripathy D, Gara M, Pearson P, DeCillis A, Meric-Bernstam F. CBX-12-101: A first-in-human study of CBX-12, an alphalex peptide drug conjugate (PDC) in patients (pts) with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2023, 41: 3087-3087. DOI: 10.1200/jco.2023.41.16_suppl.3087.Peer-Reviewed Original ResearchTreatment-related AEsOvarian cancerBreast cancerFrequent treatment-related AEsHER2-negative breast cancerPlatinum-resistant ovarian cancerDaily x 3Daily x 5Hormone receptor positiveSingle-agent antitumor activityMetastatic solid tumorsPhase 1 trialAnti-drug antibodiesNegative breast cancerAnti-tumor activityAntibody-drug conjugatesFebrile neutropeniaRECIST v1.1WBC decreaseExpansion cohortFIH studiesPlasma PKTumor cell membranesHuman studiesSolid tumors
2022
748 A phase 1/2, open-label, dose-escalation, safety and tolerability study of NC762 in subjects with advanced or metastatic solid tumors
Myint H, Shah S, Gutierrez M, Zsiros E, Nelson M, Zeidan S, Myrthil N, Morawski A, Barbu A, Shaik J, Zhou C, Kanellopoulou C, Copeland R, Cusumano Z, Flies D, Langermann S, Lorusso P, Odunsi K. 748 A phase 1/2, open-label, dose-escalation, safety and tolerability study of NC762 in subjects with advanced or metastatic solid tumors. 2022, a781-a781. DOI: 10.1136/jitc-2022-sitc2022.0748.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 ResearchPhase 1b study of the novel first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-relapsed and refractory solid malignancies and dose escalation update.
Muller C, Chaney M, Cohen J, Garyantes T, Lin J, LoRusso P, Mita A, Mita M, Natale C, Orloff M, Papadopoulos K, Patel S, Rodon Ahnert J. Phase 1b study of the novel first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-relapsed and refractory solid malignancies and dose escalation update. Journal Of Clinical Oncology 2022, 40: 2574-2574. DOI: 10.1200/jco.2022.40.16_suppl.2574.Peer-Reviewed Original ResearchG protein-coupled estrogen receptorFavorable safety profileStable diseaseLong-term benefitsHuman dose-escalation studyProtein-coupled estrogen receptorMetastatic uveal melanoma patientsEncouraging anti-tumor activityClinical benefit rateDose-escalation portionPhase 1b studyRefractory solid malignanciesImmune checkpoint inhibitorsObjective response rateDose-escalation studyMetastatic solid tumorsUveal melanoma patientsDuration of treatmentAnti-tumor activityEstrogen receptor agonistsSmall molecule agonistsCTCAE v5.0Evaluable patientsMeasurable diseaseRECIST v1.1
2021
484 Preliminary efficacy of the IL-15 superagonist SO-C101 in combination with pembrolizumab in patients with advanced/metastatic solid tumors
Garralda E, Galvao V, Champiat S, LoRusso P, Grell P, Naing A, Janku F, Sachse R, Bechard D, Kiemle-Kallee J, Marabelle A, Garralda E. 484 Preliminary efficacy of the IL-15 superagonist SO-C101 in combination with pembrolizumab in patients with advanced/metastatic solid tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a514-a514. DOI: 10.1136/jitc-2021-sitc2021.484.Peer-Reviewed Original ResearchStudy drug-related adverse eventsDrug-related adverse eventsCytokine release syndromeDose-limiting toxicityAdverse eventsCommon study drug-related adverse eventsAnti-programmed cell death protein 1 antibodyGrade 3 cytokine release syndromeSolid tumorsCell death protein 1 antibodyAnti-PD-1 therapyLong-term stable diseaseLocal injection site reactionsSkin squamous cell carcinomaPhase 2 dosePrevious systemic therapyTreatment-related deathsInjection site reactionsMetastatic solid tumorsAdditional clinical benefitDose-escalation designProtective memory responsesProtein 1 antibodySquamous cell carcinomaAvailable safety data502 Recommended phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the IL-15 superagonist SO-C101 as monotherapy in patients with advanced/metastatic solid tumors
Marabelle A, Champiat S, Galvao V, Naing A, Janku F, LoRusso P, Grell P, Sachse R, Bechard D, Kiemle-Kallee J, Garralda E. 502 Recommended phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the IL-15 superagonist SO-C101 as monotherapy in patients with advanced/metastatic solid tumors. 2021, a534-a534. DOI: 10.1136/jitc-2021-sitc2021.502.Peer-Reviewed Original ResearchPhase 2 doseDose-limiting toxicityAdverse eventsPartial responseStable diseaseTransaminase increaseSolid tumorsDrug-related adverse eventsIL-15 receptor αCutaneous squamous cell carcinomaLocal injection site reactionsPrevious systemic therapyResults Thirty patientsSignificant partial responseTreatment-related deathsCommon adverse eventsFlu-like syndromeRelated adverse eventsInjection site reactionsMetastatic solid tumorsAdditional clinical benefitDose-escalation designSquamous cell carcinomaDose-dependent increaseT cell activationA phase 1 dose-escalation study of intravenously (IV) administered TAK-676, a novel STING agonist, alone and in combination with pembrolizumab in patients (pts) with advanced or metastatic solid tumors.
Falchook G, Luke J, Strauss J, Gao X, LoRusso P, VOON P, Li C, Shaw M, Gregory R, Horn K, Gibbs J, Lineberry N, Stumpo K, Malek K, Olszanski A. A phase 1 dose-escalation study of intravenously (IV) administered TAK-676, a novel STING agonist, alone and in combination with pembrolizumab in patients (pts) with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2021, 39: tps2670-tps2670. DOI: 10.1200/jco.2021.39.15_suppl.tps2670.Peer-Reviewed Original ResearchMetastatic solid tumorsCombination armCheckpoint inhibitorsSTING agonistsNovel STING agonistSolid tumorsDose escalationEastern Cooperative Oncology Group performance status 0Anti-programmed death ligand 1 therapyDay 1Phase 1 dose-escalation studyAnti-programmed death-1Death ligand 1 therapyPerformance status 0Phase 2 doseProinflammatory tumor environmentSolid Tumors (RECIST) v.Immune checkpoint inhibitorsDose-escalation studyResponse Evaluation CriteriaInnate immune cellsPreliminary antitumor activityStandard therapeutic optionAntitumor immune mechanismsImmuno-oncology therapiesSafety and preliminary efficacy from the phase 1 portion of MasterKey-01: A First-in-human dose-escalation study to determine the recommended phase 2 dose (RP2D), pharmacokinetics (PK) and preliminary antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients (pts) with advanced solid malignancies.
Schram A, Ahnert J, Patel M, Jauhari S, Sachdev J, Zhu V, LoRusso P, Nguyen D, Le X, O'Connor M, Waters N, Cook C, Witt K, Humphrey R, Janne P, Hamilton E. Safety and preliminary efficacy from the phase 1 portion of MasterKey-01: A First-in-human dose-escalation study to determine the recommended phase 2 dose (RP2D), pharmacokinetics (PK) and preliminary antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients (pts) with advanced solid malignancies. Journal Of Clinical Oncology 2021, 39: 3086-3086. DOI: 10.1200/jco.2021.39.15_suppl.3086.Peer-Reviewed Original ResearchFE cohortHER2 amplificationSolid tumorsHuman dose-escalation studyDose-escalation cohortsManageable safety profilePhase 2 doseAdvanced solid malignanciesAdvanced solid tumorsDose-escalation studyMetastatic solid tumorsPreliminary antitumor activityPhase 1 portionAnti-tumor activityTumor growth inhibitionBID cohortQD scheduleEGFR/HER2Adverse eventsEscalation cohortsPartial responseProgressive diseaseStandard therapySafety profilePreliminary efficacy
2020
807 A multicenter open-label phase I/lb study of SO-C101 as monotherapy and in combination with pembrolizumab in patients with selected advanced/metastatic solid tumors
Marabelle A, Champiat S, Garralda E, Hernando A, Janku F, Raina A, Sachse R, Bechard D, Krasnopolskaya I, Ferrara S, LoRusso P. 807 A multicenter open-label phase I/lb study of SO-C101 as monotherapy and in combination with pembrolizumab in patients with selected advanced/metastatic solid tumors. 2020, a483.1-a483. DOI: 10.1136/jitc-2020-sitc2020.0807.Peer-Reviewed Original ResearchPhase I first-in-human study of ABBV-151 as monotherapy or in combination with budigalimab in patients with locally advanced or metastatic solid tumours
Powderly J, Shimizu T, Lorusso P, Razak A, Miller K, Balar A, Bruix J, Michel L, Blaney M, Guan X, Lacy S, Lally S, Lambert S, Leibman R, Vosganian G, Golan T, Tolcher A. Phase I first-in-human study of ABBV-151 as monotherapy or in combination with budigalimab in patients with locally advanced or metastatic solid tumours. Annals Of Oncology 2020, 31: s499. DOI: 10.1016/j.annonc.2020.08.710.Peer-Reviewed Original ResearchMasterkey-01: Phase I/II, open-label multicenter study to assess safety, tolerability, pharmacokinetics, and antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies.
Hamilton E, Patel M, Rodon J, Hong D, Schram A, Janne P, LoRusso P, Sachdev J, Ou S, Buck E, O'Connor M, Waters N, Witt K, Cook C. Masterkey-01: Phase I/II, open-label multicenter study to assess safety, tolerability, pharmacokinetics, and antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies. Journal Of Clinical Oncology 2020, 38: tps3665-tps3665. DOI: 10.1200/jco.2020.38.15_suppl.tps3665.Peer-Reviewed Original ResearchAntitumor activityStandard therapyPreliminary efficacyERBB mutationsOpen-label multicenter studySignificant unmet need existsPhase I/IIHER2 tyrosine kinase inhibitorPhase 2 doseAdvanced solid malignanciesAdequate drug exposureMetastatic solid tumorsPreliminary antitumor activityExon 20 insertionsOncogenic driver mutationsTyrosine kinase inhibitorsUnmet need existsAssessment of safetyCurrent eGFRExpansion cohortMulticenter studyPharmacodynamic effectsSolid malignanciesDrug exposureCohort 1Trial in progress: A phase I/II, open-label, dose-escalation, safety and tolerability study of NC318 in subjects with advanced or metastatic solid tumors.
Gutierrez M, Hamid O, Shum E, Wise D, Balar A, Weber J, LoRusso P, Shafi S, Rimm D, Tolcher A, Basudhar D, Dujka M, Heller K. Trial in progress: A phase I/II, open-label, dose-escalation, safety and tolerability study of NC318 in subjects with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2020, 38: tps3166-tps3166. DOI: 10.1200/jco.2020.38.15_suppl.tps3166.Peer-Reviewed Original ResearchMetastatic solid tumorsT cell functionSolid tumorsPD-L1 tumor proportion scoreAnti-tumor immune responseNon-small cell lungPhase I/IIPhase 2 doseTumor proportion scoreAnti-tumor immunityKey eligibility criteriaCell functionDose-escalation designBreast cancer subjectsNon-randomized studiesT cell proliferationPrevents tumor growthClass monoclonal antibodyCollection of biopsiesMeasurable diseaseRECIST v1.1Phase 1/2Escalation designTolerability studyImmune suppressionA First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors
Varga A, Soria JC, Hollebecque A, LoRusso P, Bendell J, Huang SA, Wagle MC, Okrah K, Liu L, Murray E, Sanabria-Bohorquez SM, Tagen M, Dokainish H, Mueller L, Burris H. A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors. Clinical Cancer Research 2020, 26: 1229-1236. PMID: 31848189, DOI: 10.1158/1078-0432.ccr-19-2574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDose-Response Relationship, DrugFatigueFemaleHumansMaleMAP Kinase Signaling SystemMaximum Tolerated DoseMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NauseaNeoplasmsPatient SafetyProtein Kinase InhibitorsPyridonesPyrimidinesTissue DistributionVomitingConceptsBRAF-mutant colorectal cancerColorectal cancerAdverse eventsFDG-PETCommon drug-related adverse eventsSolid tumorsDrug-related adverse eventsPhase IPartial metabolic responseAcceptable safety profileAdvanced solid tumorsDose-proportional increaseGrade 3 rashMetastatic solid tumorsSerial tumor biopsiesSingle-agent activityBest overall responseHuman phase IMAPK pathway inhibitionMultiple tumor typesStable diseaseEscalation studyPartial responseOral inhibitorPharmacodynamic effects
2019
466P Interim results from trial of SL-801, a novel XPO-1 inhibitor, in patients with advanced solid tumours
Wang J, Barve M, Chiorean E, LoRusso P, Courtney K, Qi D, Bullington J, Sardone M, Chen J, Brooks C, Shemesh S, Bauer T. 466P Interim results from trial of SL-801, a novel XPO-1 inhibitor, in patients with advanced solid tumours. Annals Of Oncology 2019, 30: v175. DOI: 10.1093/annonc/mdz244.028.Peer-Reviewed Original ResearchSchedule ADay 1Optimal dose/schedulePreliminary anti-tumor activityDose-escalation stageStudy dose levelsMetastatic solid tumorsDose/scheduleAggressive tumor behaviorAnti-tumor activityAssess pharmacokineticsStarting doseDose intensityStandard therapyPoor prognosisHematologic malignanciesTumor behaviorDose levelsSolid tumorsPatientsNuclear export proteinVivo activityDoseLonger recovery timeDaysA phase Ia/Ib, open label, multicenter, dose-escalation study of BI 907828 (MDM2-p53 antagonist) in adult patients with advanced or metastatic solid tumors.
Chong C, Bauer T, Laurie S, Patel M, Yamamoto N, Davenport T, Geng J, Gibson N, Vallaster M, LoRusso P. A phase Ia/Ib, open label, multicenter, dose-escalation study of BI 907828 (MDM2-p53 antagonist) in adult patients with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2019, 37: tps3166-tps3166. DOI: 10.1200/jco.2019.37.15_suppl.tps3166.Peer-Reviewed Original ResearchDose-limiting toxicityMetastatic solid tumorsFirst treatment cycleSolid tumorsEvaluable patientsPrimary endpointTreatment cyclesPhase 1bPreliminary anti-tumor activityMDM2-p53 antagonistsNon-squamous NSCLCDose-escalation studyDose-escalation trialSoft tissue sarcomasNumber of patientsTP53 wild-type statusWild-type statusAnti-tumor activityMDM2 amplification statusTumor protein 53New anti-cancer drugsIA/IBOpen labelRECIST v1.1Brain metastases
2018
A phase I study of AL101, a pan-NOTCH inhibitor, in patients (pts) with locally advanced or metastatic solid tumors.
El-Khoueiry A, Desai J, Iyer S, Gadgeel S, Ramalingam S, Horn L, LoRusso P, Bajaj G, Kollia G, Qi Z, Basak S, Fischer B, Davis M, Bedard P. A phase I study of AL101, a pan-NOTCH inhibitor, in patients (pts) with locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2018, 36: 2515-2515. DOI: 10.1200/jco.2018.36.15_suppl.2515.Peer-Reviewed Original Research
2017
90TiP A phase Ib trial of xentuzumab and abemaciclib in patients with locally advanced or metastatic solid tumors, hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer (BC; +/- endocrine therapy), or non-small-cell lung cancer (NSCLC)
Yee D, Prat A, Sablin M, Iwata H, Johnston E, Bogenrieder T, Serra J, Hua H, LoRusso P. 90TiP A phase Ib trial of xentuzumab and abemaciclib in patients with locally advanced or metastatic solid tumors, hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer (BC; +/- endocrine therapy), or non-small-cell lung cancer (NSCLC). Annals Of Oncology 2017, 28: x25. DOI: 10.1093/annonc/mdx656.001.Peer-Reviewed Original Research