2025
Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer
Qi C, Shen L, Andre T, Chung H, Cannon T, Garralda E, Italiano A, Rieke D, Liu T, Burcoveanu D, Neu N, Mussi C, Xu R, Hong D, Drilon A, Berlin J. Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer. European Journal Of Cancer 2025, 220: 115338. PMID: 40068370, DOI: 10.1016/j.ejca.2025.115338.Peer-Reviewed Original ResearchTreatment-related adverse eventsSafety of larotrectinibMicrosatellite instability-highGI cancersMedian duration of responseNext-generation sequencing testMedian overall survivalProgression-free survivalDuration of responseNTRK gene fusionsOverall response rateFirst-in-classOverall survivalMedian durationTRK inhibitorsSolid tumorsTumor typesAdverse eventsExtended survivalLarotrectinibGastrointestinal cancerPatientsHepatic cancerResponse rateCancerSafety and Antitumor Activity of a Novel aCD25 Treg Depleter RG6292 as a Single Agent and in Combination with Atezolizumab in Patients with Solid Tumors
Gambardella V, Ong M, Rodriguez-Ruiz M, Machiels J, Sanmamed M, Galvao V, Spreafico A, Renouf D, Luen S, Galot R, de Spéville B, Calvo E, Naing A, Curdt S, Kolben T, Rossmann E, Tanos T, Smart K, Amann M, Xie Y, Xu L, Alcaide E, Städler N, Justies N, Boetsch C, Karanikas V, Schnetzler G, Rohrberg K. Safety and Antitumor Activity of a Novel aCD25 Treg Depleter RG6292 as a Single Agent and in Combination with Atezolizumab in Patients with Solid Tumors. Cancer Research Communications 2025, 5: 422-432. PMID: 39983024, PMCID: PMC11891644, DOI: 10.1158/2767-9764.crc-24-0638.Peer-Reviewed Original ResearchConceptsRecommended phase II dosePhase II doseMaximum tolerated dosePhase I studyTreg depletionSolid tumorsII doseTolerated doseResistance to cancer immunotherapyRegulatory T-cell depletionImmunosuppressive regulatory T cellsEffector T cell functionAdvanced solid tumorsT-cell depletionRegulatory T cellsAnti-CD25 antibodyFrequent adverse eventsT cell functionDose-dependent depletionIL-2 signalingAtezolizumab combinationDeplete TregsTreg reductionDose escalationPeripheral TregsNanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers
Champiat S, Garralda E, Galvao V, Cassier P, Gomez-Roca C, Korakis I, Grell P, Naing A, LoRusso P, Mikyskova R, Podzimkova N, Reinis M, Ouali K, Schoenenberger A, Kiemle-Kallee J, Tillmanns S, Sachse R, Moebius U, Spisek R, Bechard D, Jelinkova L, Adkins I, Marabelle A. Nanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers. Cell Reports Medicine 2025, 6: 101967. PMID: 39933529, PMCID: PMC11866505, DOI: 10.1016/j.xcrm.2025.101967.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsNatural killerT cellsAnti-programmed cell death protein 1Frequent treatment-emergent adverse eventsProportion of CD8<sup>+</sup> T cellsAnti-PD-1 pembrolizumabTreatment-emergent adverse eventsCell death protein 1Anti-PD-1Advanced/metastatic solid tumorsStimulated natural killerInjection site reactionsIL-15 receptorMouse tumor modelsPD-1NK cellsPeripheral bloodIL-15Safety profileSite reactionsSolid tumorsClinical efficacyAdverse eventsTumor modelOlaparib in treatment‐refractory isocitrate dehydrogenase 1 (IDH1)– and IDH2‐mutant cholangiocarcinoma: Safety and antitumor activity from the phase 2 National Cancer Institute 10129 trial
Cecchini M, Pilat M, Uboha N, Azad N, Cho M, Davis E, Ahnert J, Tinoco G, Shapiro G, Khagi S, Powers B, Spencer K, Groisberg R, Drappatz J, Chen L, Das B, Bao X, Li J, Narayan A, Vu D, Patel A, Niger M, Doroshow D, Durecki D, Boerner S, Bindra R, Ivy P, Shyr D, Shyr Y, LoRusso P. Olaparib in treatment‐refractory isocitrate dehydrogenase 1 (IDH1)– and IDH2‐mutant cholangiocarcinoma: Safety and antitumor activity from the phase 2 National Cancer Institute 10129 trial. Cancer 2025, 131: e35755. PMID: 39917990, DOI: 10.1002/cncr.35755.Peer-Reviewed Original ResearchConceptsProgression-free survivalHomologous recombination deficiencyClinical benefitNational Cancer InstituteIDH inhibitorsMedian progression-free survivalAccumulation of 2-hydroxyglutaratePhase 2 clinical trialIsocitrate dehydrogenase inhibitorsMedian overall survivalSingle-agent activityNovel combination therapiesEnhance patient selectionSubgroup of patientsOverall survivalOpen-labelCombination therapyIDH mutationsPatient selectionRecombination deficiencySolid tumorsTumor progressionClinical trialsOlaparibCholangiocarcinomaSelective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500.
Appleman V, Matsuda A, Ganno M, Zhang D, Rosentrater E, Maldonado Lopez A, Porciuncula A, Hatten T, Christensen C, Merrigan S, Lee H, Lee M, Wang C, Dong L, Huang J, Iartchouk N, Wang J, Xu H, Yoneyama T, Piatkov K, Haridas S, Harbison C, Gregory R, Parent A, Lineberry N, Arendt C, Schalper K, Abu-Yousif A. Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody Drug Conjugate TAK-500. Cancer Immunology Research 2025 PMID: 39918395, DOI: 10.1158/2326-6066.cir-24-0103.Peer-Reviewed Original ResearchIntratumoral myeloid cellsMyeloid cellsTumor microenvironmentImmune responseCCR2+ cellsI interferonImmunosuppressive myeloid populationsImmune activation in vitroImmune cell markersLocal immune activationMurine tumor modelsAdaptive immune responsesAntibody drug conjugatesType I interferonAntitumor immunityInnate immune responseMyeloid populationsSTING agonistsSolid tumorsCCR2 proteinImmune activationTumor modelCell markersHuman tumorsAdaptive immunityEVEREST-2: A seamless phase 1/2 study of A2B694, a logic-gated Tmod chimeric antigen receptor T-cell (CAR T) therapy, in patients with pancreatic cancer (PANC) or other mesothelin (MSLN)-expressing solid tumors and human leukocyte antigen (HLA)–A*02 loss of heterozygosity (LOH).
Spencer K, Punekar S, Grierson P, Mitchell J, Lin Y, Biachi de Castria T, Zhen D, Vu P, Morelli M, Kundranda M, Dorigo O, Maloney D, Ward J, Eng C, Maus M, Simeone D, Welch J, Molina J, Go W, Hecht J. EVEREST-2: A seamless phase 1/2 study of A2B694, a logic-gated Tmod chimeric antigen receptor T-cell (CAR T) therapy, in patients with pancreatic cancer (PANC) or other mesothelin (MSLN)-expressing solid tumors and human leukocyte antigen (HLA)–A*02 loss of heterozygosity (LOH). Journal Of Clinical Oncology 2025, 43: tps788-tps788. DOI: 10.1200/jco.2025.43.4_suppl.tps788.Peer-Reviewed Original ResearchOff-tumor toxicityCAR-T therapyPancreatic cancerHLA-A*02T cellsSolid tumorsCAR-TT therapyNormal cellsChimeric antigen receptor T cellsRecommended phase 2 doseT cell receptor therapyNon-small cell lungCryopreserved T cellsPhase 2 doseDose-expansion phaseProgression-free survivalTumor-associated antigensCAR-T activityObjective of Phase 1First-in-humanOverall response rateOn-targetDose escalationMSLN expressionAutogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial
Lopez J, Powles T, Braiteh F, Siu L, LoRusso P, Friedman C, Balmanoukian A, Gordon M, Yachnin J, Rottey S, Karydis I, Fisher G, Schmidt M, Schuler M, Sullivan R, Burris H, Galvao V, Henick B, Dirix L, Jaeger D, Ott P, Wong K, Jerusalem G, Schiza A, Fong L, Steeghs N, Leidner R, Rittmeyer A, Laurie S, Gort E, Aljumaily R, Melero I, Sabado R, Rhee I, Mancuso M, Muller L, Fine G, Yadav M, Kim L, Leveque V, Robert A, Darwish M, Qi T, Zhu J, Zhang J, Twomey P, Rao G, Low D, Petry C, Lo A, Schartner J, Delamarre L, Mellman I, Löwer M, Müller F, Derhovanessian E, Cortini A, Manning L, Maurus D, Brachtendorf S, Lörks V, Omokoko T, Godehardt E, Becker D, Hawner C, Wallrapp C, Albrecht C, Kröner C, Tadmor A, Diekmann J, Vormehr M, Jork A, Paruzynski A, Lang M, Blake J, Hennig O, Kuhn A, Sahin U, Türeci Ö, Camidge D. Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial. Nature Medicine 2025, 31: 152-164. PMID: 39762422, PMCID: PMC11750724, DOI: 10.1038/s41591-024-03334-7.Peer-Reviewed Original ResearchConceptsCD8+ T cellsAdvanced solid tumorsT cellsSolid tumorsCirculating CD8+ T cellsEfficacy of cancer immunotherapyTumor-infiltrating T cellsStimulate T cell responsesResponse to immunotherapyT cell responsesPreliminary antitumor activityPhase 1 studyPhase 1 trialDose escalationPretreated patientsCancer immunotherapyEvaluation of pharmacokineticsCD4+Tumor lesionsTreatment initiationTumor tissuesAtezolizumabClinical activityDisease characteristicsImmunotherapy
2024
A novel pharmacological entity toward integrated multimodal immunotherapy
Sirera R, Beltrán-Visiedo M, Galluzzi L. A novel pharmacological entity toward integrated multimodal immunotherapy. Trends In Pharmacological Sciences 2024, 46: 95-97. PMID: 39721827, DOI: 10.1016/j.tips.2024.12.001.Peer-Reviewed Original ResearchFinancial Toxicity Among Patients With Advanced Solid Tumors Participating in Early-Phase Clinical Trials.
Blanter J, Van Hyfte G, Ahmad M, Xu S, Hapanowicz O, Fazilov G, Lu A, Lucas N, Wu K, Shelton G, DeMerchant M, Lachowicz M, Kier M, Werner M, Eder J, Galsky M, Marron T, Smith C, LoRusso P, Hofstatter E, Doroshow D. Financial Toxicity Among Patients With Advanced Solid Tumors Participating in Early-Phase Clinical Trials. JCO Oncology Practice 2024, op2400293. PMID: 39661920, DOI: 10.1200/op.24.00293.Peer-Reviewed Original ResearchEarly-phase clinical trialsSolid tumorsClinical trialsAssociated with higher FTFinancial toxicityBarriers to clinical trial enrollmentAdvanced solid malignanciesAdvanced solid tumorsInverse association with ageBaseline to 2 monthsYale Cancer CenterCOST scoreClinical trial enrollmentProspective survey studySolid malignanciesNo significant differenceBaseline FTTime of consentNovel therapiesPrimary outcomeCancer CenterSurvey 1Trial enrollmentPatientsEarly-phaseA Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer
Jia J, Moyer A, Lowe M, Bolch E, Kortmansky J, Cho M, Lenz H, Kalyan A, Niedzwiecki D, Strickler J. A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer. Journal Of Gastrointestinal Cancer 2024, 56: 29. PMID: 39652198, DOI: 10.1007/s12029-024-01156-x.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsMetastatic colorectal cancerPhase 2 studyEpidermal growth factor receptorAnti-tumor activityStable diseaseProgressive diseaseChemotherapy refractory metastatic colorectal cancerOral small-molecule tyrosine kinase inhibitorColorectal cancerResistance to epidermal growth factor receptorSmall molecule tyrosine kinase inhibitorsRefractory metastatic colorectal cancerBest overall responseRAS wild-typeAdvanced solid tumorsBiomarker-selected patientsTyrosine kinase inhibitorsWild-typeGrowth factor receptorResultsFive patientsPrimary endpointSecondary endpointsSolid tumorsSavolitinibDeep learning for oncologic treatment outcomes and endpoints evaluation from CT scans in liver cancer
Xia Y, Zhou J, Xun X, Johnston L, Wei T, Gao R, Zhang Y, Reddy B, Liu C, Kim G, Zhang J, Zhao S, Yu Z. Deep learning for oncologic treatment outcomes and endpoints evaluation from CT scans in liver cancer. Npj Precision Oncology 2024, 8: 263. PMID: 39551847, PMCID: PMC11570623, DOI: 10.1038/s41698-024-00754-z.Peer-Reviewed Original ResearchProgression-free survivalCT scanLiver cancerAccurate treatment response assessmentResponse evaluationMetastatic organ sitesOncological treatment outcomesResponse Evaluation CriteriaLow-risk patientsTreatment response assessmentTreatment response evaluationTreatment response classificationAdvanced liver cancerStratify high-riskMultifocal hepatic lesionsTreatment outcome assessmentEvaluation of responseOverall survivalEvaluation CriteriaInternal five-fold cross-validationOncology clinical trialsResponse assessmentSolid tumorsClinical trialsTreatment outcomesTargeting T-Cell Costimulation to the Surface of Tumor Cells.
Eguren-Santamaría I, Sanmamed M, Molero-Glez P, Perez-Gracia J, Melero I. Targeting T-Cell Costimulation to the Surface of Tumor Cells. Clinical Cancer Research 2024, 31: 231-233. PMID: 39531541, DOI: 10.1158/1078-0432.ccr-24-3003.Peer-Reviewed Original ResearchT lymphocytesTumor cellsTargeting T-cell costimulationSurface of tumor cellsT cell costimulationProportion of patientsT cell activationAntitumor responseT cellsSolid tumorsSurface antigensActivator receptorSignal 2CostimulationTumorTarget specificityCellsCD137HER2Novel evidencePatientsAntigenReceptorsLactate fermentation intoxicates TILs
Hunt B, Kessler E, Joshi N. Lactate fermentation intoxicates TILs. Nature Immunology 2024, 25: 2176-2177. PMID: 39516647, DOI: 10.1038/s41590-024-02020-7.Peer-Reviewed Original Research627 EVEREST-2: a seamless phase 1/2 study of A2B694, a logic-gated Tmod CAR T-cell therapy, in patients with mesothelin-expressing solid tumors with human leukocyte antigen-A*02 loss of heterozygosity
Molina J, Hazim A, Dorigo O, Punekar S, Avila M, Simeone D, Kirtane K, Konecny G, Ward J, Block M, Specht J, Boyd L, Lou Y, Park J, Xuan J, Eskander R, Ong G, Davila M, Langeberg W, Maus M, Mardiros A, Locke F, Wise A, Maloney D, Welch J, Randolph Hecht J. 627 EVEREST-2: a seamless phase 1/2 study of A2B694, a logic-gated Tmod CAR T-cell therapy, in patients with mesothelin-expressing solid tumors with human leukocyte antigen-A*02 loss of heterozygosity. 2024, a721-a722. DOI: 10.1136/jitc-2024-sitc2024.0627.Peer-Reviewed Original Research662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors
Mitchell S, Khan B, Payumo F, Gabriela Chiorean E, Gahvari Z, Randolph Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Schoenfeld A, Punekar S, Zhao D, Basu S, Nagorsen D. 662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors. 2024, a759-a759. DOI: 10.1136/jitc-2024-sitc2024.0662.Peer-Reviewed Original Research758 GLIMMER-01: phase 1/2 trial of a first-in-class bi-sialidase (E-602) in combination with cemiplimab in patients with PD-(L)1-resistant solid tumors
Sharma M, Johnson M, Puzanov I, Sznol M, Mckean M, Gainor J, Spira A, Henick B, Tolcher A, Chen C, El-Khoueiry A, Broderick J, Peng L, Che J, Cao L, Wilson D, Lathers D, Horak C, Feltquate D, Luke J. 758 GLIMMER-01: phase 1/2 trial of a first-in-class bi-sialidase (E-602) in combination with cemiplimab in patients with PD-(L)1-resistant solid tumors. 2024, a862-a862. DOI: 10.1136/jitc-2024-sitc2024.0758.Peer-Reviewed Original ResearchPhase 1/2 trialSolid tumorsMetabolic Determinants of Ferroptosis in B-Cell Lymphoma
Leveille E, Bramson E, Robinson M, Bertomeu T, Chatr-Aryamontri A, Kothari S, Müschen M. Metabolic Determinants of Ferroptosis in B-Cell Lymphoma. Blood 2024, 144: 976-976. DOI: 10.1182/blood-2024-209077.Peer-Reviewed Original ResearchB-cell lymphomaB-cell malignanciesB cellsSensitivity to ferroptosisLipid membrane remodelingFerroptosis inducersMyeloid leukemiaSolid tumorsMembrane remodelingCRISPR screensGene dependenciesAssociated with significantly worse survivalTreatment of B-cell lymphomaB-cell lymphoma modelElimination of B cellsPUFA metabolismCysteine-glutamate antiporterCell deathMature splenic B cellsTherapy-resistant tumorsNon-apoptotic form of cell deathAnalysis of clinical dataDominant-negative p53Vulnerability to ferroptosisWhole-genome CRISPR screenFirst-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 dosesKeratin 17 and A2ML1 are negative prognostic biomarkers in non-small cell lung cancer
Babu S, Horowitz M, Delgado-Coka L, Roa-Peña L, Akalin A, Escobar-Hoyos L, Shroyer K. Keratin 17 and A2ML1 are negative prognostic biomarkers in non-small cell lung cancer. Pathology - Research And Practice 2024, 263: 155643. PMID: 39413460, DOI: 10.1016/j.prp.2024.155643.Peer-Reviewed Original ResearchNon-small cell lung cancerLung squamous cell carcinomaNegative prognostic biomarkerCell lung cancerSquamous cell carcinomaPancreatic ductal adenocarcinomaPrognostic biomarkerCell carcinomaMultiplex immunohistochemistryPrognostic accuracyDuctal adenocarcinomaLung cancerPrimary lung squamous cell carcinomaHead and neck squamous cell carcinomaNeck squamous cell carcinomaImpact treatment decisionsClinicopathological factorsClinicopathological variablesOverall prognosisPulmonary adenocarcinomaSolid tumorsNon-smallSurvival differencesPrognostic dataCo-testingModern Photon-Based Craniospinal Irradiation in Leptomeningeal Disease
Keit E, Peterson J, Johnstone P, Robinson T, Figura N. Modern Photon-Based Craniospinal Irradiation in Leptomeningeal Disease. International Journal Of Radiation Oncology • Biology • Physics 2024, 120: e242. DOI: 10.1016/j.ijrobp.2024.07.542.Peer-Reviewed Original ResearchIntensity modulated radiotherapyCraniospinal irradiationLeptomeningeal diseaseHematologic malignanciesSolid tumorsOverall survivalProton therapyLocal failureAssociated with improved OSDelay systemic therapyG3+ toxicitySymptomatic leptomeningeal diseaseSite of spreadKaplan Meier methodPhoton-based treatmentsPrimary cancer typeAcute gradeG3 fatigueMedian OSModulated radiotherapyNeutropenic feverMedian followPalliative radiotherapyDisseminated diseaseSystemic therapy
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