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, 30: 2576-2585. PMID: 38942995, PMCID: PMC11405272, 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 arms
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 disease
2022
Nivolumab 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 observationsPatients
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 ageEvaluation of cabozantinib (cabo) in combination with direct oral anticoagulants (DOAC) or low molecular weight heparin (LMWH) in renal cell carcinoma (RCC).
Mesleh Shayeb A, Urman D, Dizman N, Meza L, Sivakumar A, Gan C, Dzimitrowicz H, Zhang T, Barata P, Bilen M, Gao X, Heng D, Pal S, Kaymakcalan M, McGregor B, Choueiri T, McKay R. Evaluation of cabozantinib (cabo) in combination with direct oral anticoagulants (DOAC) or low molecular weight heparin (LMWH) in renal cell carcinoma (RCC). Journal Of Clinical Oncology 2021, 39: 291-291. DOI: 10.1200/jco.2021.39.6_suppl.291.Peer-Reviewed Original ResearchLow molecular weight heparinDirect oral anticoagulantsRenal cell carcinomaAdvanced renal cell carcinomaMajor bleeding eventsVenous thromboembolismBleeding eventsMajor bleedingSafety profileDifferent anticoagulantsSimilar bleeding riskRecurrent venous thromboembolismClear cell histologyRetrospective multicenter studyMolecular weight heparinCause of deathFisher's exact testLMWH useRCC outcomeBleeding riskMedian doseOral anticoagulantsPrimary endpointSecondary endpointsVTE events