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. 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 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 Research608O Preliminary safety and clinical activity of ASP3082, a first-in-class, KRAS G12D selective protein degrader in adults with advanced pancreatic (PC), colorectal (CRC), and non-small cell lung cancer (NSCLC)
Park W, Kasi A, Spira A, Berlin J, Wang J, Herzberg B, Kuboki Y, Kitano S, Pelster M, Goldman J, Morgensztern D, Kondo S, Jänne P, Fujii H, Lee H, Gill S, Saci A, Lorusso P, Tolcher A. 608O Preliminary safety and clinical activity of ASP3082, a first-in-class, KRAS G12D selective protein degrader in adults with advanced pancreatic (PC), colorectal (CRC), and non-small cell lung cancer (NSCLC). Annals Of Oncology 2024, 35: s486-s487. DOI: 10.1016/j.annonc.2024.08.675.Peer-Reviewed Original Research1000MO 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 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 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 Research691TiP PYNNACLE phase II trial of rezatapopt (PC14586) in solid tumors with a TP53 Y220C mutation
Schram A, Lopes G, El-Khoueiry A, Fontana E, Karasic T, Kummar S, Lorusso P, Gregorc V, Millward M, Aix S, Richardson D, Perez D, Spira A, Tan D, Thompson J, Uprety D, Fellous M, Qin Y, Dumbrava E. 691TiP PYNNACLE phase II trial of rezatapopt (PC14586) in solid tumors with a TP53 Y220C mutation. Annals Of Oncology 2024, 35: s535-s536. DOI: 10.1016/j.annonc.2024.08.2162.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 tissuesA Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170)
Maldonado E, Rathmell W, Shapiro G, Takebe N, Rodon J, Mahalingam D, Trikalinos N, Kalebasty A, Parikh M, Boerner S, Balido C, Krings G, Burns T, Bergsland E, Munster P, Ashworth A, LoRusso P, Aggarwal R. A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170). Cancer Research Communications 2024, 4: 1793-1801. PMID: 38920407, PMCID: PMC11264598, DOI: 10.1158/2767-9764.crc-24-0213.Peer-Reviewed Original ResearchSolid tumor malignanciesStable diseaseTumor malignancyAdverse eventsDepth of tumor responseLoss of H3K36me3Median duration of treatmentAdvanced solid tumor malignanciesClear cell renal cell carcinomaMinor tumor regressionsProlonged stable diseaseArchival tumor tissuePhase II studyCell renal cell carcinomaPhase II trialRenal cell carcinomaDuration of treatmentArchival tissue samplesSimon's two-stageTumor responseTumor regressionII trialMedian durationII studySETD2 mutationsAuthor Correction: Inhibition of lysine acetyltransferase KAT6 in ER+HER2− metastatic breast cancer: a phase 1 trial
Mukohara T, Park Y, Sommerhalder D, Yonemori K, Hamilton E, Kim S, Kim J, Iwata H, Yamashita T, Layman R, Mita M, Clay T, Chae Y, Oakman C, Yan F, Kim G, Im S, Lindeman G, Rugo H, Liyanage M, Saul M, Le Corre C, Skoura A, Liu L, Li M, LoRusso P. Author Correction: Inhibition of lysine acetyltransferase KAT6 in ER+HER2− metastatic breast cancer: a phase 1 trial. Nature Medicine 2024, 30: 2371-2371. PMID: 38914862, PMCID: PMC11333270, DOI: 10.1038/s41591-024-03129-w.Peer-Reviewed Original ResearchUnlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates.
Ascione L, Guidi L, Prakash A, Trapani D, LoRusso P, Lou E, Curigliano G. Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates. American Society Of Clinical Oncology Educational Book 2024, 44: e431766. PMID: 38828973, DOI: 10.1200/edbk_431766.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesTumor sitePredictive biomarkersAntigen expressionLack of robust predictive biomarkersSelection of targeted therapiesRobust predictive biomarkersTarget antigen expressionTumor antigen expressionCancer treatment landscapeBiomarkers of responseImprove patient selectionTumor intrinsic featuresBiomarkers of safetyUnique adverse eventsIdentification of patientsPopulation of patientsClinically actionable biomarkersSmall-molecule agentsPatient-centred outcomesTreatment landscapeBiomarker-drivenTreatment resistanceClinical benefitPatient selectionPhase 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 careFirst-in-human phase I trial of the oral first-in-class ubiquitin specific peptidase 1 (USP1) inhibitor KSQ-4279 (KSQi), given as single agent (SA) and in combination with olaparib (OLA) or carboplatin (CARBO) in patients (pts) with advanced solid tumors, enriched for deleterious homologous recombination repair (HRR) mutations.
Yap T, Lakhani N, Patnaik A, Lee E, Gutierrez M, Moore K, Carneiro B, Hays J, Huang M, LoRusso P, Wylie A, Cadzow L, Goulet M, Tobin E, Krieter O, Schmid D, Blake S, Dieterich M, Jamois C, Harris P. First-in-human phase I trial of the oral first-in-class ubiquitin specific peptidase 1 (USP1) inhibitor KSQ-4279 (KSQi), given as single agent (SA) and in combination with olaparib (OLA) or carboplatin (CARBO) in patients (pts) with advanced solid tumors, enriched for deleterious homologous recombination repair (HRR) mutations. Journal Of Clinical Oncology 2024, 42: 3005-3005. DOI: 10.1200/jco.2024.42.16_suppl.3005.Peer-Reviewed Original ResearchUbiquitin specific peptidase 1Treatment-emergent adverse eventsHomologous recombination repair mutationsSingle agentPARP inhibitorsHomologous recombination repairFirst-in-human phase I trialPreliminary anti-tumor activityPaired tumor biopsiesTNBC PDX modelsDisease control ratePhase I trialAUC 4Olaparib concentrationsRECIST PRDose escalationExpansion cohortCancer ptsDose proportionalityTumor biopsiesI trialMaculopapular rashPDX modelsDiscontinued treatmentDNA damage response pathwayA phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation.
Stockton S, Shyr C, Cecchini M, Aljumaily R, Halfdanarson T, Sonbol M, Whisenant J, Ivy S, LoRusso P, Das S, Gore S, Berlin J, Beumer J, Heumann T. A phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation. Journal Of Clinical Oncology 2024, 42: 3076-3076. DOI: 10.1200/jco.2024.42.16_suppl.3076.Peer-Reviewed Original ResearchMaximum tolerated doseDose escalationDose levelsMedian progression-free survivalRecommended phase 2 doseRefractory advanced solid tumorsResults of dose escalationTreatment-related adverse eventsSmall cell lung cancerDisease control ratePhase 2 dosePhase Ia studyDose-limiting toxicityProgression-free survivalAdvanced solid tumorsPhase I studyCell lung cancerAnti-tumor activityExpansion cohortPartial responseTolerated doseTopotecan exposureStudy drugCancer xenograftsRespiratory failureA phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer.
Mukohara T, Park Y, Sommerhalder D, Yonemori K, Kim S, Kim J, Iwata H, Yamashita T, Layman R, Kim G, Im S, Lindeman G, Rugo H, Liyanage M, Homji Mishra N, Maity A, Bogg O, Liu L, Li M, LoRusso P. A phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer. Journal Of Clinical Oncology 2024, 42: 3006-3006. DOI: 10.1200/jco.2024.42.16_suppl.3006.Peer-Reviewed Original ResearchHER2- metastatic breast cancerTreatment-related adverse eventsMetastatic breast cancerCirculating tumor DNABreast cancerGene mutationsFrequent treatment-related adverse eventsMedian duration of follow-upAntitumor activityDuration of follow-upClinical benefit rateProgression-free survivalHER2 breast cancerMutant allele frequencyExpansion doseFulvestrant combinationMedian DoRESR1 mutationsMetastatic settingDose modificationEndocrine therapySystemic therapyMedian durationTumor DNACDK4/6 inhibitors