2024
First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors
Shimizu T, Powderly J, Razak A, LoRusso P, Miller K, Kao S, Kongpachith S, Tribouley C, Graham M, Stoll B, Patel M, Sahtout M, Blaney M, Leibman R, Golan T, Tolcher A. First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors. Frontiers In Oncology 2024, 14: 1376551. PMID: 39534099, PMCID: PMC11555770, DOI: 10.3389/fonc.2024.1376551.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-escalation phaseDose escalationSolid tumorsSurface of regulatory T cellsRecommended phase 2 doseSuppress antitumor immune responsesCombination therapy cohortsDose-proportional PKMonotherapy-treated patientsPhase 2 doseMedian response durationAntitumor immune responseDose-limiting toxicityTherapy-treated patientsRegulatory T cellsMaximum administered doseFirst-in-humanDose escalation resultsGlycoprotein A repetitionsPromote tumor growthBlood biomarker dataDose expansionPretreated patientsEscalating doses1 Oral: First Clinical Results from A Phase 1 Trial of PRT3789, a First-in-Class Intravenous SMARCA2 Degrader, in Patients with Advanced Solid Tumors with a SMARCA4 Mutation
Yap T, Dowlati A, Dagogo-Jack I, Vibert J, Spira A, Garcia V, Punekar S, Calvo E, Sonpavde G, Awad M, Riess J, Hernández-Guerrero T, Herzberg B, Italiano A, Swalduz A, LoRusso P, Smit E, Garon E, Novotny W, Guo R. 1 Oral: First Clinical Results from A Phase 1 Trial of PRT3789, a First-in-Class Intravenous SMARCA2 Degrader, in Patients with Advanced Solid Tumors with a SMARCA4 Mutation. European Journal Of Cancer 2024, 211: 114530. DOI: 10.1016/j.ejca.2024.114530.Peer-Reviewed Original Research603O First clinical results from a phase I trial of PRT3789: A first-in-class intravenous SMARCA2 degrader, in patients with advanced solid tumors with a SMARCA4 mutation
Guo R, Dowlati A, Dagogo-Jack I, Vibert J, Spira A, Garcia V, Punekar S, Calvo E, Sonpavde G, Awad M, Riess J, Guerrero T, Herzberg B, Italiano A, Swalduz A, Lorusso P, Smit E, Garon E, Novotny W, Yap T. 603O First clinical results from a phase I trial of PRT3789: A first-in-class intravenous SMARCA2 degrader, in patients with advanced solid tumors with a SMARCA4 mutation. Annals Of Oncology 2024, 35: s483-s484. DOI: 10.1016/j.annonc.2024.08.670.Peer-Reviewed Original Research616MO Long-term follow-up of single-agent divarasib in patients with KRAS G12C-positive solid tumors
Garralda E, Patel M, Kim T, Sacher A, Forster M, Santoro A, Desai J, Paz-Ares L, Gonzalez A, De Miguel M, Bowyer S, Dziadziuszko R, Kim S, Han S, Krebs M, Lorusso P, Cosman R, Chang J, Jun T, Miller W. 616MO Long-term follow-up of single-agent divarasib in patients with KRAS G12C-positive solid tumors. Annals Of Oncology 2024, 35: s494. DOI: 10.1016/j.annonc.2024.08.683.Peer-Reviewed Original ResearchLong-term follow-upSolid tumors1000MO A phase I/II, open-label study of the novel checkpoint IGSF8 inhibitor GV20-0251 in patients with advanced solid tumors
Wentzel K, Peguero J, Kummar S, Lorusso P, Mehnert J, Spira A, Naing A, Hamid O, Mehmi I, Benhadji K, Alland L, Hu X, Xiao H, Bao X, Chen J, Gong Y, Liu X. 1000MO A phase I/II, open-label study of the novel checkpoint IGSF8 inhibitor GV20-0251 in patients with advanced solid tumors. Annals Of Oncology 2024, 35: s680-s681. DOI: 10.1016/j.annonc.2024.08.1059.Peer-Reviewed Original Research669P CBX-12-101: Final results of a phase I study of CBX-12, a peptide drug conjugate (PDC) in patients (pts) with metastatic solid tumors
Lorusso P, Meric-Bernstam F, Hafez N, Rivera I, Tripathy D, Wilks S, Pearson P, Needle M, Tolcher A. 669P CBX-12-101: Final results of a phase I study of CBX-12, a peptide drug conjugate (PDC) in patients (pts) with metastatic solid tumors. Annals Of Oncology 2024, 35: s525. DOI: 10.1016/j.annonc.2024.08.735.Peer-Reviewed Original Research990O Final results from phase I, first-in-human, dose escalation study of a first-in-class anti-ILT2 antibody, SAR444881, alone and with pembrolizumab 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, Friedman I, Hakim M, Ziv D, Hashmueli S, Mandel I, Moshe T, Crawford N, Abbadessa G, Perez R, Wu M, Borad M. 990O Final results from phase I, first-in-human, dose escalation study of a first-in-class anti-ILT2 antibody, SAR444881, alone and with pembrolizumab or cetuximab, in patients with advanced solid tumors. Annals Of Oncology 2024, 35: s675. DOI: 10.1016/j.annonc.2024.08.1049.Peer-Reviewed Original Research996MO Dazostinag (TAK-676) alone and in combination with pembrolizumab (pembro) in patients (pts) with advanced/metastatic solid tumors: Data from phase I dose escalation
Luke J, Gao X, Olszanski A, Sanborn R, Falchook G, Patel S, Bedard P, Orr D, Gibbs J, Li C, Huang Y, Gregory R, Ramesh R, Xu R, Wu B, Ding K, Raizer J, Lorusso P. 996MO Dazostinag (TAK-676) alone and in combination with pembrolizumab (pembro) in patients (pts) with advanced/metastatic solid tumors: Data from phase I dose escalation. Annals Of Oncology 2024, 35: s678-s679. DOI: 10.1016/j.annonc.2024.08.1055.Peer-Reviewed Original Research439TiP AVZO-021-1001: A first-in-human open-label, multicenter phase I/II dose-escalation and expansion study evaluating AVZO-021 in adult patients with advanced solid tumors
Dowlati A, Richardson D, Lorusso P, Spira A, Bashir B, Hirmand M, Mehta M, Patel M. 439TiP AVZO-021-1001: A first-in-human open-label, multicenter phase I/II dose-escalation and expansion study evaluating AVZO-021 in adult patients with advanced solid tumors. Annals Of Oncology 2024, 35: s405. DOI: 10.1016/j.annonc.2024.08.386.Peer-Reviewed Original ResearchCirculating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors
Choi Y, Dharia N, Jun T, Chang J, Royer-Joo S, Yau K, Assaf Z, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman J, Shi Z, group A. Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors. Clinical Cancer Research 2024, 30: of1-of10. PMID: 38995268, PMCID: PMC11369623, DOI: 10.1158/1078-0432.ccr-24-0255.Peer-Reviewed Original ResearchConceptsKRAS G12C mutationTumor fractionSolid tumorsTumor typesG12C mutationOn-treatment time pointsNon-small cell lung cancerMutational heterogeneityAssociated with tumor typeProgression-free survivalPlasma samplesPhase 1 studyCell lung cancerCycle 1 dayAssociated with patient outcomesVariant allele frequencyAssociated with responseCtDNA levelsCtDNA profilingMetastatic sitesTruncal mutationsTumor DNATreatment responseLung cancerTumor tissuesPhase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors.
Falchook G, LoRusso P, Goldman J, El-Khoueiry A, Tolcher A, Xing Y, Henry J, Keam B, Kim D, Kim T, Kim H, Hong M, Kim M, Lee D, Lee S, Jeon J, Hayslip J, Xu C, Garon E. Phase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors. Journal Of Clinical Oncology 2024, 42: 2529-2529. DOI: 10.1200/jco.2024.42.16_suppl.2529.Peer-Reviewed Original ResearchTreatment related adverse eventsClinical benefit rateOverall response ratePD-L1Dose levelsPD-(L)1Complete responsePartial responseSolid tumorsHead and neck squamous cellAntibody targeting PD-L1Treated with checkpoint inhibitorsActivation of T cellsDose-limiting toxicityPre-treated patientsPD-(L)1 inhibitorsDose-expansion cohortRelapsed/refractory solid tumorsWeight-based dosingLines of treatmentPD-L1 antagonistsRelated adverse eventsAnti-tumor effectsDose-dependent increaseMultiple tumor typesA phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation.
Heumann T, Stockton S, Cecchini M, Aljumaily R, Shyr C, Whisenant J, Starr J, Dayyani F, Baranda J, Trikalinos N, Ivy S, LoRusso P, Das S, Gore S, Beumer J, Berlin J. A phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation. Journal Of Clinical Oncology 2024, 42: 3077-3077. DOI: 10.1200/jco.2024.42.16_suppl.3077.Peer-Reviewed Original ResearchAdvanced solid tumorsMaximum tolerated doseDose escalationSolid tumorsPhase I study of irinotecanRecommended phase 2 doseRefractory advanced solid tumorsPhase 2 dosePhase I studyAnti-tumor activityBiweekly irinotecanInhibitor irinotecanIrinotecan exposureWeekly irinotecanTolerated doseDosing scheduleCancer xenograftsAdult patientsIrinotecanAssess safetyATR inhibitorsElimusertibSecondary objectivesDoseStandard careResults from phase 1a/1b analyses of TTX-080, a first in class HLA-G antagonist, in combination with cetuximab in patients (pts) with metastatic colorectal cancer and head and neck squamous cell carcinoma.
Ulahannan S, Marron T, Park H, Kaczmar J, Stephenson R, Lakhani N, Durm G, Grewal J, El-Khoueiry A, Luke J, Beers C, Murugappan S, LoRusso P, Adkins D, Hecht J. Results from phase 1a/1b analyses of TTX-080, a first in class HLA-G antagonist, in combination with cetuximab in patients (pts) with metastatic colorectal cancer and head and neck squamous cell carcinoma. Journal Of Clinical Oncology 2024, 42: 2524-2524. DOI: 10.1200/jco.2024.42.16_suppl.2524.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaMetastatic colorectal cancerNeck squamous cell carcinomaSquamous cell carcinomaPreliminary efficacy dataCell carcinomaColorectal cancerEfficacy dataSolid tumor cohortTreatment-related AEsImmune cell changesAnti-tumor activityStandard of careRandomized controlled studyDose escalationEscalating dosesHLA-G.Peripheral bloodTumor cohortsSolid tumorsDecreased appetiteAST increaseBlood samplesCell changesQ3W61MO Phase Ia/Ib study of the MDM2-p53 antagonist brigimadlin (BI 907828) in advanced solid tumours: Overall safety, and efficacy in patients (pts) with well-differentiated liposarcoma (WDLPS)
Reichardt P, Schöffski P, Lorusso P, Yamamoto N, Garcia V, Lugowska I, Lauer U, Somaiah N, Hu C, Landsteiner H, Jayadeva G, Gounder M. 61MO Phase Ia/Ib study of the MDM2-p53 antagonist brigimadlin (BI 907828) in advanced solid tumours: Overall safety, and efficacy in patients (pts) with well-differentiated liposarcoma (WDLPS). ESMO Open 2024, 9: 102451. DOI: 10.1016/j.esmoop.2024.102451.Peer-Reviewed Original ResearchCirculating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors
Hu Y, Narayan A, Xu Y, Wolfe J, Vu D, Trinh T, Kantak C, Ivy S, Eder J, Deng Y, LoRusso P, Kim J, Patel A. Circulating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors. JCO Precision Oncology 2024, 8: e2300289. PMID: 38412387, PMCID: PMC10914240, DOI: 10.1200/po.23.00289.Peer-Reviewed Original ResearchConceptsCell-free circulating tumor DNANon-small-cell lung cancerSmall-cell lung cancerTriple-negative breast cancerPancreatic ductal adenocarcinomaAdvanced solid tumorsVariant allele fractionRadiographic responseOverall survivalCombination therapySolid tumorsCtDNA levelsLung cancerPretreated advanced solid tumorsDays of combination therapyMetastatic pancreatic ductal adenocarcinomaResponse to anticancer therapyAssociated with disease progressionProgression-free survivalPlasma samplesLead-inPoly(ADP-riboseInferior OSTumor DNASurvival outcomesEfficacy and safety of brigimadlin (BI 907828), an MDM2–p53 antagonist, in patients (pts) with advanced biliary tract cancer: Data from two phase Ia/Ib dose-escalation/expansion trials.
Macarulla T, Yamamoto N, Tolcher A, Hafez N, Lugowska I, Ramlau R, Geng J, Li J, Teufel M, Maerten A, LoRusso P. Efficacy and safety of brigimadlin (BI 907828), an MDM2–p53 antagonist, in patients (pts) with advanced biliary tract cancer: Data from two phase Ia/Ib dose-escalation/expansion trials. Journal Of Clinical Oncology 2024, 42: 487-487. DOI: 10.1200/jco.2024.42.3_suppl.487.Peer-Reviewed Original ResearchBiliary tract cancerTreatment-related AEsAdvanced biliary tract cancerMonotherapy trialsStable diseasePartial responseCombination trialsMouse double minute 2MDM2-p53 antagonistsEscalating dosesSolid tumorsCases of biliary tract cancerTP53 wild-type tumorsAnti-PD-1 antibodyStandard-of-care chemotherapyData cut-offWild-type tumorsAdvanced/metastatic solid tumorsResponding ptsMDM2-p53MDM2 amplified tumorsDouble minute 2MDM2-amplifiedAmpullary adenocarcinomaCell cycle arrestPharmacokinetics (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 Research608 Results of a phase 1 study investigating camidanlumab tesirine as monotherapy and in combination with pembrolizumab in patients with selected advanced solid tumors
Chen C, Hamilton E, LoRusso P, Rottey S, Papadopoulos K, Kummar S, Kotecki N, Thistlethwaite F, LeBruchec Y, Dyczkowski J, Rüschoff J, Samari S, Toukam M, Boni J, Havenith K, Pantano S, Puzanov I. 608 Results of a phase 1 study investigating camidanlumab tesirine as monotherapy and in combination with pembrolizumab in patients with selected advanced solid tumors. 2023, a692-a692. DOI: 10.1136/jitc-2023-sitc2023.0608.Peer-Reviewed Original ResearchAnti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors
Kim T, Bedard P, LoRusso P, Gordon M, Bendell J, Oh D, Ahn M, Garralda E, D’Angelo S, Desai J, Hodi F, Wainberg Z, Delord J, Cassier P, Cervantes A, Gil-Martin M, Wu B, Patil N, Jin Y, Hoang T, Mendus D, Wen X, Meng R, Cho B. Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors. JAMA Oncology 2023, 9: 1574-1582. PMID: 37768658, PMCID: PMC10540058, DOI: 10.1001/jamaoncol.2023.3867.Peer-Reviewed Original ResearchConceptsObjective response rateAdvanced solid tumorsAdverse eventsPhase 1bAntitumor activityCancer cohortNon-small cell lung cancer (NSCLC) cohortFrequent treatment-related adverse eventsInvestigator-assessed objective response rateSolid tumorsCell lung cancer cohortTreatment-related adverse eventsMajority of AEsEnd pointClinical cutoff dateDose-escalation cohortsDose-expansion cohortsEsophageal cancer cohortPhase 2 dosePrior cancer therapyPrimary end pointSecondary end pointsHalf of patientsNew safety signalsAntitumor immune response