2024
OA10.05 Phase I Trial of DLL3/CD3 IgG-Like T-Cell Engager BI 764532 in Patients with DLL3-Positive Tumors: Patients with LCNEC
Wermke M, Gambardella V, Kuboki Y, Alese O, Morgensztern D, Sayehli C, Sanmamed M, Arriola E, Wolf J, Villaruz L, Studeny M, Bouzaggou M, Fang X, Felip E. OA10.05 Phase I Trial of DLL3/CD3 IgG-Like T-Cell Engager BI 764532 in Patients with DLL3-Positive Tumors: Patients with LCNEC. Journal Of Thoracic Oncology 2024, 19: s32. DOI: 10.1016/j.jtho.2024.09.059.Peer-Reviewed Original ResearchA phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer
Planchard D, Wolf J, Solomon B, Sebastian M, Wermke M, Heist R, Sun J, Min Kim T, Reguart N, Sanmamed M, Felip E, Garrido P, Santoro A, Bootle D, Couillebault X, Gaur A, Mueller C, Poggio T, Yang J, Moschetta M, Dooms C. A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. Lung Cancer 2024, 197: 107964. PMID: 39383771, DOI: 10.1016/j.lungcan.2024.107964.Peer-Reviewed Original ResearchNon-small cell lung cancerCell lung cancerBRAF-mutated non-small cell lung cancerLung cancerDose-escalation/dose-expansion studyTreatment-related adverse eventsAntitumor activityDose-limiting toxicityNRAS-mutant melanomaMEK1/2 inhibitor trametinibPartial responseInhibitor trametinibFrequent gradeSafety profileAdverse eventsPharmacodynamic effectsTrametinibGenetic alterationsMedian reductionPan-RAFIncreased lipasePatientsSecondary objectivesMRNA levelsEvaluate toleranceSequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma.
Ascierto P, Mandalà M, Ferrucci P, Guidoboni M, Rutkowski P, Ferraresi V, Arance A, Guida M, Maiello E, Gogas H, Richtig E, Quaglino P, Lebbé C, Helgadottir H, Queirolo P, Spagnolo F, Tucci M, Del Vecchio M, Gonzalez-Cao M, Minisini A, De Placido S, Sanmamed M, Casula M, Bulgarelli J, Pisano M, Piccinini C, Piccin L, Cossu A, Mallardo D, Paone M, Vitale M, Melero I, Grimaldi A, Giannarelli D, Palmieri G, Dummer R, Sileni V. Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma. NEJM Evidence 2024, 3: evidoa2400087. PMID: 39315864, DOI: 10.1056/evidoa2400087.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionBrain metastasesBRAF/MEK inhibitorsArm BArm AProgressive diseaseCheckpoint inhibitionBrain metastases-free survivalImmune checkpoint inhibitor ipilimumabMetastases-free survival ratesDevelopment of brain metastasesCheckpoint inhibitor ipilimumabMetastases-free survivalUnresectable metastatic melanomaV600-mutant melanomaCheckpoint inhibitorsInhibitor ipilimumabMetastatic melanomaBRAF/MEK inhibitionArm CReviewed patientsBRAF/MEKThree-arm trialEncorafenibFollow-upMHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers
Eguren-Santamaria I, de Piérola E, Camps G, Martín-Muñoz P, Campos M, Cuculescu D, Aguilera-Buenosvinos I, López I, Salido-Vallejo R, Alexandru R, De Andrea C, Álvarez-Gigli L, Berraondo P, Melero I, Sanmamed M. MHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers. Journal For ImmunoTherapy Of Cancer 2024, 12: e008516. PMID: 39244214, PMCID: PMC11381650, DOI: 10.1136/jitc-2023-008516.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsT-cell engagersNSG miceMajor histocompatibility complexSevere XGVHDImmunodeficient miceAntitumor effectTumor rejectionImmunotherapy agentsAntitumor activityAntitumor efficacy of immune checkpoint inhibitorsEfficacy of immune checkpoint inhibitorsHT29 human colon carcinoma cellsLong-term antitumor efficacyDevelopment of cancer immunotherapyAdministration of nivolumabImmune checkpoint inhibitorsCancer immunotherapy agentsT cell clonesHuman colon carcinoma cellsAlanine aminotransferase levelsMajor histocompatibility complex class IBlood mononuclear cellsHuman immune cells670P Phase I trial of the delta-like ligand-3 (DLL3)/CD3 IgG-Like T cell engager BI 764532 in patients (pts) with DLL3-positive tumors: Updated data
Wermke M, Gambardella V, Kuboki Y, Felip E, Sanmamed M, Alese O, Sayehli C, Aperribay E, Wolf J, Villaruz L, Studeny M, Bouzaggou M, Fang X, Morgensztern D. 670P Phase I trial of the delta-like ligand-3 (DLL3)/CD3 IgG-Like T cell engager BI 764532 in patients (pts) with DLL3-positive tumors: Updated data. Annals Of Oncology 2024, 35: s525-s526. DOI: 10.1016/j.annonc.2024.08.736.Peer-Reviewed Original ResearchCN59 Activity and outcomes of a Translational Research Unit coordinated by nursing
Andueza M, Zabalza E, Barberena Y, Burgui M, Ilundain I, Andueza I, Perea A, Andueza M, Sanmamed M, RodrÍguez-Ruiz M, Pio R, Hernandez A, Fortuño M, de Torres J, Maceiras L, Lozano M, Melero I, Montuenga L, Gracia J, Ocon M. CN59 Activity and outcomes of a Translational Research Unit coordinated by nursing. Annals Of Oncology 2024, 35: s1186. DOI: 10.1016/j.annonc.2024.08.463.Peer-Reviewed Original ResearchThyroid dysfunction caused by immune checkpoint inhibitors improves cancer outcomes.
García-Goñi M, Vázquez Gutiérrez B, Sanmamed M, Martín-Algarra S, Luis Pérez-Gracia J, Olmedo M, Chumbiauca E, Martín-Calvo N, Galofré J. Thyroid dysfunction caused by immune checkpoint inhibitors improves cancer outcomes. Endocrine Related Cancer 2024, 31 PMID: 39013402, DOI: 10.1530/erc-24-0064.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsImmune-related adverse eventsRisk of progressionOverall survivalPrimary tumorThyroid dysfunctionPatients treated with immune checkpoint inhibitorsCancer patients treated with immune checkpoint inhibitorsAssociated with higher ORRImmune checkpoint inhibitor regimenTreated with atezolizumabLonger overall survivalCox proportional hazards modelsResponse to treatmentProbability of recurrenceMultivariable-adjusted regressionRisk of mortalityProportional hazards modelIndependent of ageCheckpoint inhibitorsRECIST v1.1Higher ORRCombination therapyUrothelial cancerClinical presentationProtein Biomarkers in Lung Cancer Screening: Technical Considerations and Feasibility Assessment
Orive D, Echepare M, Bernasconi-Bisio F, Sanmamed M, Pineda-Lucena A, de la Calle-Arroyo C, Detterbeck F, Hung R, Johansson M, Robbins H, Seijo L, Montuenga L, Valencia K. Protein Biomarkers in Lung Cancer Screening: Technical Considerations and Feasibility Assessment. Archivos De Bronconeumología 2024, 60: s67-s76. PMID: 39079848, DOI: 10.1016/j.arbres.2024.07.007.Peer-Reviewed Original ResearchLung cancer screeningLung cancerCancer screeningManagement of lung cancerLDCT-based lung cancer screeningSurgically resected tumorsPresence of metastasesEarly lung cancerCancer-related deathsLung cancer patientsContext of lung cancer screeningDiagnosis to earlier stagesProtein biomarkersResected tumorProtein-based biomarkersTherapeutic optionsAdjuvant strategiesLate diagnosisCancer patientsRecommended management strategiesEarly managementLung cancer detectionRobust biomarkersBenefit patientsCancerShort-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism
Eguren-Santamaría I, Rodríguez I, Herrero-Martin C, de Piérola E, Azpilikueta A, Sánchez-Gregorio S, Bolaños E, Gomis G, Molero-Glez P, Chacón E, Mínguez J, Chiva S, Diez-Caballero F, de Andrea C, Teijeira Á, Sanmamed M, Melero I. Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism. OncoImmunology 2024, 13: 2373519. PMID: 38988823, PMCID: PMC11236292, DOI: 10.1080/2162402x.2024.2373519.Peer-Reviewed Original ResearchConceptsTumor fragmentsImmunotherapy combinationsIFNg productionActivation markersClinical response to PD-1 blockadeResponse to PD-1 blockadeAgonistic anti-CD137 mAbAnti-PD-1 treatmentAnti-CD137 mAbAnti-PD-1PD-1 blockadeSyngeneic immunocompetent miceInfiltrating T cellsShort-term cultureUnmet medical needAnti-CD137Contralateral tumorsBilateral tumorsCancer immunotherapyTissue culture supernatantsImmunocompetent miceSolid malignanciesT cellsMAb combinationsMouse tumorsKROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC.
Gregorc V, González-Cao M, Salvagni S, Koumarianou A, Gil-Bazo I, Maio M, Viteri S, Majem M, Gutiérrez V, Bernabe Caro R, Sanmamed M, Zhu H, Shen H, Wang Y, Rosell R. KROCUS: A phase II study investigating the efficacy and safety of fulzerasib (GFH925) in combination with cetuximab in patients with previously untreated advanced KRAS G12C mutated NSCLC. Journal Of Clinical Oncology 2024, 42: lba8511-lba8511. DOI: 10.1200/jco.2024.42.17_suppl.lba8511.Peer-Reviewed Original ResearchTreatment-related adverse eventsDisease control ratePhase II studyEpidermal growth factor receptorKRAS G12C inhibitorsDose reduction/interruptionBrain metastasesII studySafety profileG12C inhibitorsBaseline PD-L1 expressionBaseline brain metastasesActivation of epidermal growth factor receptorPD-L1 expressionTreating NSCLC patientsAnti-EGFR antibodiesFront-line treatmentKRAS G12C mutationGrowth factor receptorNSCLC ptsNSCLC modelsTumor shrinkageFrontline therapyNSCLC patientsOpen-labelUp-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulatedPhase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure
Spreafico A, Couselo E, Irmisch A, Bessa J, Au-Yeung G, Bechter O, Svane I, Sanmamed M, Gambardella V, McKean M, Callahan M, Dummer R, Klein C, Umaña P, Justies N, Heil F, Fahrni L, Opolka-Hoffmann E, Waldhauer I, Bleul C, Staack R, Karanikas V, Fowler S. Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure. Frontiers In Oncology 2024, 14: 1346502. PMID: 38577337, PMCID: PMC10991832, DOI: 10.3389/fonc.2024.1346502.Peer-Reviewed Original ResearchTreatment-related adverse eventsAnti-drug antibodiesCytokine release syndromeFirst-in-humanT-cell engagersCheckpoint inhibitorsMetastatic melanomaT cellsDrug exposureDevelopment of anti-drug antibodiesActive drugImmune responseFirst-in-human studyDrug activity in vitroDose-escalation studyDose-escalation trialTumor necrosis factor-alphaB cell interactionsImpact of immune responsesActive drug exposureNecrosis factor-alphaAnti-tumor activityLoss of efficacyAssociated with developmentDose escalationWhole exome sequencing and machine learning germline analysis of individuals presenting with extreme phenotypes of high and low risk of developing tobacco-associated lung adenocarcinoma
Patiño-García A, Guruceaga E, Andueza M, Ocón M, Sokoudjou J, de Villalonga Zornoza N, Alkorta-Aranburu G, Uria I, Gurpide A, Camps C, Jantus-Lewintre E, Navamuel-Andueza M, Sanmamed M, Melero I, Elgendy M, Fusco J, Zulueta J, de-Torres J, Bastarrika G, Seijo L, Pio R, Montuenga L, Hernáez M, Ochoa I, Perez-Gracia J. Whole exome sequencing and machine learning germline analysis of individuals presenting with extreme phenotypes of high and low risk of developing tobacco-associated lung adenocarcinoma. EBioMedicine 2024, 102: 105048. PMID: 38484556, PMCID: PMC10955643, DOI: 10.1016/j.ebiom.2024.105048.Peer-Reviewed Original ResearchHeavy smokersWhole-exome sequencingGermline profilingLung cancerLow riskLung adenocarcinomaCoding genetic variantsIdentification of high-risk subjectsIndividual variantsHigh-risk subjectsSequencing germline DNATobacco consumptionDiscovery cohortAdvanced agePack-yearsExome sequencingProfile of subjectsRisk factorsGenetic variantsYounger ageSmokersFunding bodiesTobaccoCohortAnalysis of individualsPD-1H/VISTA mediates immune evasion in acute myeloid leukemia
Kim T, Han X, Hu Q, Vandsemb E, Fielder C, Hong J, Kim K, Mason E, Plowman R, Wang J, Wang Q, Zhang J, Badri T, Sanmamed M, Zheng L, Zhang T, Alawa J, Lee S, Zeidan A, Halene S, Pillai M, Chandhok N, Lu J, Xu M, Gore S, Chen L. PD-1H/VISTA mediates immune evasion in acute myeloid leukemia. Journal Of Clinical Investigation 2024, 134 PMID: 38060328, PMCID: PMC10836799, DOI: 10.1172/jci164325.Peer-Reviewed Original ResearchSequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial
Ascierto P, Casula M, Bulgarelli J, Pisano M, Piccinini C, Piccin L, Cossu A, Mandalà M, Ferrucci P, Guidoboni M, Rutkowski P, Ferraresi V, Arance A, Guida M, Maiello E, Gogas H, Richtig E, Fierro M, Lebbe C, Helgadottir H, Queirolo P, Spagnolo F, Tucci M, Del Vecchio M, Cao M, Minisini A, De Placido S, Sanmamed M, Mallardo D, Paone M, Vitale M, Melero I, Grimaldi A, Giannarelli D, Dummer R, Sileni V, Palmieri G. Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial. Nature Communications 2024, 15: 146. PMID: 38167503, PMCID: PMC10761671, DOI: 10.1038/s41467-023-44475-6.Peer-Reviewed Original ResearchConceptsOverall survivalSurvival outcomesNoncomparative phase II trialTotal progression-free survivalLong-term survival outcomesMEK inhibitionBRAF/MEK inhibitionFirst-line treatment approachFirst-line treatment optionBRAF/MEK inhibitorsT-lymphocyte antigen-4Cell death protein 1BRAFV600-mutant melanomaDual checkpoint blockadeFirst-line immunotherapyMetastatic BRAF V600Serum interferon gammaPhase II trialProgression-free survivalDeath protein 1BRAFV600-mutant metastatic melanomaLow baseline levelsBiomarker analysisCombination BRAFSequential immunotherapy
2023
OA01.05 Phase I Dose Escalation Trial Of The DLL3/CD3 Igg-Like T Cell Engager BI 764532 In Patients with DLL3+ Tumors: Focus on SCLC
Wermke M, Kuboki Y, Felip E, Alese O, Morgensztern D, Sayehli C, Arriola E, Sanmamed M, Hamed Z, Song E, Studeny M, Gambardella V. OA01.05 Phase I Dose Escalation Trial Of The DLL3/CD3 Igg-Like T Cell Engager BI 764532 In Patients with DLL3+ Tumors: Focus on SCLC. Journal Of Thoracic Oncology 2023, 18: s45-s46. DOI: 10.1016/j.jtho.2023.09.026.Peer-Reviewed Original Research75MO Phase I trial of the DLL3/CD3 IgG-like T cell engager BI 764532 in patients (pts) with DLL3+ tumors: Focus on Asian pts
Kuboki Y, Gambardella V, Castillon J, Alese O, Morgensztern D, Sayehli C, Sanmamed M, Arriola E, Wolf J, Owonikoko T, Studeny M, Bouzaggou M, Song E, Wermke M. 75MO Phase I trial of the DLL3/CD3 IgG-like T cell engager BI 764532 in patients (pts) with DLL3+ tumors: Focus on Asian pts. Annals Of Oncology 2023, 34: s1495. DOI: 10.1016/j.annonc.2023.10.210.Peer-Reviewed Original Research516MO Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, combined with osimertinib, as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC)
Cappuzzo F, Garcia V, Ou S, Brandão M, Sanmamed M, Helissey C, Wislez M, Call J, Grisanti S, Johnson M, Boni V, Jamme P, Monnet I, Siena S, Yan C, Barasa B, Richard B, Joe A, Laus G, Felip E. 516MO Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, combined with osimertinib, as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC). Annals Of Oncology 2023, 34: s1671. DOI: 10.1016/j.annonc.2023.10.595.Peer-Reviewed Original Research