2024
Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial
Ebrahimi H, Dizman N, Meza L, Malhotra J, Li X, Dorff T, Frankel P, Llamas-Quitiquit M, Hsu J, Zengin Z, Alcantara M, Castro D, Mercier B, Chawla N, Chehrazi-Raffle A, Barragan-Carrillo R, Jaime-Casas S, Govindarajan A, Gillece J, Trent J, Lee P, Parks T, Takahashi M, Hayashi A, Kortylewski M, Caporaso J, Lee K, Tripathi A, Pal S. Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nature Medicine 2024, 1-10. PMID: 38942995, DOI: 10.1038/s41591-024-03086-4.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalRenal cell carcinomaCell carcinomaToxicity profileAbundance of Bifidobacterium sppControl armTreatment-naive participantsFirst-line treatmentPhase 1 studyPhase 1 trialSarcomatoid componentOpen-labelHistological confirmationPrimary endpointSecondary endpointsNo significant differenceClear cellNivolumabInvestigator-initiatedClinical outcomesCabozantinibClinical activityStool samplesStudy armsCombination nivolumab and ipilimumab with and without camu camu in first-line treatment of metastatic renal cell carcinoma (mRCC).
Barragan-Carrillo R, Chawla N, Salgia N, Meza L, Zengin Z, Li X, Dizman N, Ebrahimi H, Hsu J, Castro D, Mercier B, Dorff T, Tripathi A, Bergerot C, Bergerot P, Chehrazi-Raffle A, Pal S. Combination nivolumab and ipilimumab with and without camu camu in first-line treatment of metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2024, 42: tps491-tps491. DOI: 10.1200/jco.2024.42.4_suppl.tps491.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitionBaseline to weekFirst-line treatmentClinical responsePoor-risk metastatic renal cell carcinomaFirst-line treatment of metastatic renal cell carcinomaTreatment of metastatic renal cell carcinomaCombination of immune checkpoint inhibitionEfficacy of anti-PD1 therapyCombination immune checkpoint inhibitionDual immune checkpoint inhibitionCD8+ T cellsAnti-PD1 therapyImmune-related toxicitiesProgression-free survivalWeeks of therapyReduced tumor sizeTyrosine kinase inhibitorsSingle-center trialRenal cell carcinomaClear-cell RCCMouse tumor modelsOne-sided type I errorCombination nivolumab
2023
Effect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial.
Ebrahimi H, Meza L, Lee K, Malhotra J, Alcantara M, Zengin Z, Dizman N, Govindarajan A, Hsu J, Llamas-Quitiquit M, Chawla N, Castro D, Mercier B, Liu S, Chehrazi-Raffle A, Dorff T, Frankel P, Li X, Pal S, Tripathi A. Effect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial. Journal Of Clinical Oncology 2023, 41: lba104-lba104. DOI: 10.1200/jco.2023.41.17_suppl.lba104.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalTyrosine kinase inhibitorsPrimary endpointClinical outcomesStool specimensDual immune checkpoint inhibitorsMedian progression-free survivalImproved progression-free survivalOne-sided type I errorBifidobacterium sppGrade 3/4 toxicitiesImmune checkpoint inhibitorsStudy's primary endpointWeeks of treatmentDose/scheduleRandomized clinical trialsRenal cell carcinomaEligible ptsPo bidSystemic immunomodulationCheckpoint inhibitorsSecondary endpointsLine therapyMetastatic diseaseImplications of ethnicity among patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (nivo/ipi).
Leong S, Ali S, Zengin Z, Meza L, Dizman N, Ebrahimi H, Govindarajan A, Castro D, Li X, Kim T, Melamed S, Onyshchenko M, Pal S, Chehrazi-Raffle A. Implications of ethnicity among patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (nivo/ipi). Journal Of Clinical Oncology 2023, 41: 613-613. DOI: 10.1200/jco.2023.41.6_suppl.613.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalSafety-net healthcare systemComprehensive cancer centerShorter progression-free survivalHistory of nephrectomyTertiary care centerOverall survivalLatinx patientsMRCC patientsClinical outcomesCare centerHealthcare systemHope Comprehensive Cancer CenterPoor-risk diseaseTertiary oncology centerImmune checkpoint inhibitorsLos Angeles County DepartmentMedian overall survivalRisk classificationClear cell histologyFirst-line therapyNumber of comorbiditiesKaplan-Meier methodBody mass indexAssociation between time-of-day of the immune checkpoint inhibitor (ICI) infusion and disease outcomes among patients with metastatic renal cell carcinoma (mRCC).
Dizman N, Govindarajan A, Zengin Z, Meza L, Tripathi N, Sayegh N, Castro D, Chan E, Lee K, Prajapati S, Feng M, Loo V, Pace M, O'brien S, Bailey E, Barragan-Carrillo R, Chehrazi-Raffle A, Li X, Agarwal N, Pal S. Association between time-of-day of the immune checkpoint inhibitor (ICI) infusion and disease outcomes among patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2023, 41: 678-678. DOI: 10.1200/jco.2023.41.6_suppl.678.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaMedian overall survivalOverall survivalHazard ratioPotential confoundersMedian TTFDisease outcomeMultivariate analysisCox proportional hazards modelEfficacy of ICIsObjective response ratePoor-risk diseaseProgression-free survivalSecond-line treatmentClear cell histologyRenal cell carcinomaProportional hazards modelBaseline characteristicsFree survivalCell histologyMedian ageRisk diseaseTreatment failureEntire cohortCell carcinoma
2022
Genomic and Clinical Prognostic Factors in Patients With Advanced Urothelial Carcinoma Receiving Immune Checkpoint Inhibitors
Chawla N, Sayegh N, Tripathi N, Govindarajan A, Zengin Z, Phillip E, Dizman N, Meza L, Muddasani R, Chehrazi-Raffle A, Malhotra J, Hsu J, Agarwal N, Pal S, Tripathi A. Genomic and Clinical Prognostic Factors in Patients With Advanced Urothelial Carcinoma Receiving Immune Checkpoint Inhibitors. Clinical Genitourinary Cancer 2022, 21: 69-75. PMID: 36509613, DOI: 10.1016/j.clgc.2022.11.007.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall response rateTumor mutational burdenOverall survivalWorse OSPrimary diseaseMultivariate analysisMedian progression-free survivalImmune checkpoint inhibitor therapyInferior progression-free survivalPromoter mutationsWorse progression-free survivalCheckpoint inhibitor therapyMedian overall survivalImmune checkpoint inhibitorsTertiary cancer centerClinical prognostic factorsPrimary tumor siteTERT promoter mutationsCheckpoint inhibitorsInhibitor therapyLaboratory parametersPrognostic factorsCancer CenterFemale sexTemporal Characteristics of Adverse Events of Tivozanib and Sorafenib in Previously Treated Kidney Cancer
Zengin Z, Pal S, McDermott D, Escudier B, Hutson T, Porta C, Verzoni E, Atkins M, Kasturi V, Rini B. Temporal Characteristics of Adverse Events of Tivozanib and Sorafenib in Previously Treated Kidney Cancer. Clinical Genitourinary Cancer 2022, 20: 553-557. PMID: 36096984, DOI: 10.1016/j.clgc.2022.08.005.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaRenal cell carcinomaDose modificationSorafenib armAdverse eventsCell carcinomaVascular endothelial growth factor receptor inhibitorEndothelial growth factor receptor inhibitorImproved progression-free survivalGrowth factor receptor inhibitorsProgression-free survivalDuration of toxicityMeasurable diseaseOpen labelFree survivalPrimary endpointTreatment discontinuationTreatment armsReceptor inhibitorsDose reductionKidney cancerTRAEsPatientsTivozanibSorafenibA phase I trial to evaluate the biologic effect of CBM588 ( Clostridium butyricum ) in combination with cabozantinib plus nivolumab for patients with metastatic renal cell carcinoma (mRCC).
Meza L, Malhotra J, Zengin Z, Dizman N, Hsu J, Chawla N, Chehrazi-Raffle A, Muddasani R, Govindarajan A, Castro D, Dorff T, Lyou Y, Frankel P, Pal S. A phase I trial to evaluate the biologic effect of CBM588 ( Clostridium butyricum ) in combination with cabozantinib plus nivolumab for patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2022, 40: tps4606-tps4606. DOI: 10.1200/jco.2022.40.16_suppl.tps4606.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaClinical responseClear cell metastatic renal cell carcinomaTyrosine kinase inhibitor cabozantinibBiologic effectsGut microbiomeImmune checkpoint inhibitor nivolumabOne-sided type I errorPhase I clinical trialFirst-line treatmentProgression-free survivalStudy's primary endpointCheckpoint inhibitor nivolumabPhase I trialPhase 1 trialSubgroup of patientsWeeks of treatmentCytokines/chemokinesDose/scheduleOngoing phase IRenal cell carcinomaImproved clinical benefitBifidobacterium sppEligible patientsPo bidDistinct outcomes in Hispanic/Latinx and non-Hispanic/Latinx patients with metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab plus nivolumab (ipi/nivo).
Ali S, Leong S, Meza L, Dizman N, Zengin Z, Kim T, Pak Y, Onyshchenko M, Pal S, Chehrazi-Raffle A. Distinct outcomes in Hispanic/Latinx and non-Hispanic/Latinx patients with metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab plus nivolumab (ipi/nivo). Journal Of Clinical Oncology 2022, 40: 4554-4554. DOI: 10.1200/jco.2022.40.16_suppl.4554.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaIpi/nivoProgression-free survivalTertiary care centerSafety-net healthcare systemCare centerHispanic/LatinxMultivariate Cox proportional hazards regressionShorter progression-free survivalCox proportional hazards regressionSafety-net hospital systemHope Comprehensive Cancer CenterFirst-line ipilimumabFirst-line therapyImmune checkpoint inhibitorsLos Angeles County DepartmentClear cell histologyNumber of comorbiditiesKaplan-Meier methodProportional hazards regressionComprehensive cancer centerHealthcare systemRenal cell carcinomaMultiple social determinantsReal-world analysisNivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial
Dizman N, Meza L, Bergerot P, Alcantara M, Dorff T, Lyou Y, Frankel P, Cui Y, Mira V, Llamas M, Hsu J, Zengin Z, Salgia N, Salgia S, Malhotra J, Chawla N, Chehrazi-Raffle A, Muddasani R, Gillece J, Reining L, Trent J, Takahashi M, Oka K, Higashi S, Kortylewski M, Highlander SK, Pal SK. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nature Medicine 2022, 28: 704-712. PMID: 35228755, PMCID: PMC9018425, DOI: 10.1038/s41591-022-01694-6.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaProgression-free survivalRenal cell carcinomaCell carcinomaCheckpoint inhibitorsResponse rateGut microbiomePoor-risk diseaseTreatment-naive patientsSingle-center studyPhase 1 trialRandomized phase 1 trialSignificant differencesBifidobacterium sppMechanism of actionNivolumab-ipilimumabSarcomatoid histologyPrimary endpointSecondary endpointsImmune compartmentStudy armsClinical outcomesClear cellsClinical observationsPatientsAssociation between TERT promoter mutations and clinical outcome with immune checkpoint inhibitor therapy for advanced urothelial cancer.
Chawla N, Tripathi N, Sayegh N, Govindarajan A, Dizman N, Zengin Z, Meza L, Muddasani R, Chehrazi-Raffle A, Salgia S, Malhotra J, Hsu J, Philip E, Bergerot C, Lyou Y, Swami U, Gupta S, Maughan B, Agarwal N, Pal S. Association between TERT promoter mutations and clinical outcome with immune checkpoint inhibitor therapy for advanced urothelial cancer. Journal Of Clinical Oncology 2022, 40: 561-561. DOI: 10.1200/jco.2022.40.6_suppl.561.Peer-Reviewed Original ResearchProgression-free survivalObjective response rateImmune checkpoint inhibitorsICI therapyOverall survivalTERT promoter mutationsBladder cancerFirst-line ICI therapyImmune checkpoint inhibitor therapyAdvanced urothelial cancerSubsequent-line therapyUpper tract diseaseCheckpoint inhibitor therapySuperior overall survivalMetastatic bladder cancerMuscle-invasive diseaseTertiary cancer centerRoutine clinical careCancer Genome Atlas (TCGA) databaseLarge independent cohortsPromoter mutationsTERT mutation statusCheckpoint inhibitorsMetastatic settingVariant histology
2021
First results of a randomized phase IB study comparing nivolumab/ipilimumab with or without CBM-588 in patients with metastatic renal cell carcinoma.
Meza L, Dizman N, Bergerot P, Dorff T, Lyou Y, Frankel P, Mira V, Llamas M, Hsu J, Zengin Z, Salgia N, Salgia S, Malhotra J, Chawla N, Chehrazi-Raffle A, Gillece J, Reining L, Trent J, Highlander S, Pal S. First results of a randomized phase IB study comparing nivolumab/ipilimumab with or without CBM-588 in patients with metastatic renal cell carcinoma. Journal Of Clinical Oncology 2021, 39: 4513-4513. DOI: 10.1200/jco.2021.39.15_suppl.4513.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalNivolumab/ipilimumabRenal cell carcinomaCBM 588Response rateClinical outcomesWeek 12Cell carcinomaSarcomatoid Metastatic Renal Cell CarcinomaMedian progression-free survivalGut microbiomeGrade 3/4 toxicitiesPhase Ib studyKey eligibility criteriaDiagnosis of sarcomaIMDC criteriaEvaluable patientsPrimary endpointSecondary endpointsICI responseMetastatic diseaseSarcomatoid featuresIntermediate riskMedian age