Harriet Kluger, MD
Harvey and Kate Cushing Professor of Medicine (Oncology) and of DermatologyCards
About
Research
Overview
Medical Research Interests
Medical Oncology; Melanoma
Publications
2025
Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases.
Weiss S, Djureinovic D, Wei W, Tran T, Austin M, Markowitz J, Eroglu Z, Khushalani N, Hegde U, Cohen J, Sznol M, Anderson G, Johnson B, Piteo C, Mahajan A, Adeniran A, Jilaveanu L, Goldberg S, Chiang V, Forsyth P, Kluger H. Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases. Journal Of Clinical Oncology 2025, jco2402219. PMID: 40048689, DOI: 10.1200/jco-24-02219.Peer-Reviewed Original ResearchMelanoma brain metastasesOverall survivalBrain metastasesAnti-vascular endothelial growth factor therapyMedian intracranial progression-free survivalFour-year OS ratesIntracranial progression-free survivalResponse rateCirculating angiopoietin-2Median overall survivalTrial of pembrolizumabYears of pembrolizumabDose of bevacizumabProgression-free survivalPhase II trialGrowth factor therapyAdverse event ratesAssociated with responseOS ratesPD-1Radiation necrosisLocal therapyOn-therapyMetastatic tumorsFactor therapyReal-world outcomes with T-VEC in patients with anti-PD-1 resistant in-transit disease from melanoma and Merkel cell carcinoma
Su D, McNamara M, Kaszycki M, Frey A, Ishizuka J, Costa P, Tran T, Kluger H, Clune J, Weiss S, Olino K. Real-world outcomes with T-VEC in patients with anti-PD-1 resistant in-transit disease from melanoma and Merkel cell carcinoma. Surgical Oncology Insight 2025, 2: 100120. DOI: 10.1016/j.soi.2024.100120.Peer-Reviewed Original ResearchMerkel cell carcinomaMerkel cell carcinoma casesT-VECCell carcinomaMedian numberAnti-PD-1 blockadeStage IIIB-IV melanomaAdvanced Merkel cell carcinomaIn-transit melanomaIn-transit diseaseICI therapyTalimogene laherparepvecAdvanced melanomaCancer immunotherapyMetastatic sitesPartial responseIn-transitRegional metastasesMedian ageGrade 3Adverse eventsTreatment cyclesDisease progressionMelanomaPatientsSurvival of patients with metastatic renal cell carcinoma with or without brain metastases.
Hurwitz M, Considine B, Hasson N, Savion Gaiger N, Nelson M, Chiang V, Kluger H, Braun D, Schoenfeld D, Sznol M, Leapman M. Survival of patients with metastatic renal cell carcinoma with or without brain metastases. Journal Of Clinical Oncology 2025, 43: 476-476. DOI: 10.1200/jco.2025.43.5_suppl.476.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaImmune checkpoint inhibitorsClear cell RCCRenal cell carcinomaImmune checkpoint inhibitor therapyMetastatic clear cell RCCBrain metastasesOverall survivalCell carcinomaImmune checkpoint inhibitor eraPrevalence of brain metastasesMultivariate Cox proportional hazards modelAssociated with poor survivalMedian overall survivalAssociated with poor prognosisCompare overall survivalImproved overall survivalAdverse prognostic indicatorDevelopment of BMSurvival of patientsKaplan-Meier analysisYale Cancer CenterRetrospective cohort studyCox proportional hazards modelsProportional hazards model
2024
Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial
Choueiri T, Kuzel T, Tykodi S, Verzoni E, Kluger H, Nair S, Perets R, George S, Gurney H, Pachynski R, Folefac E, Castonguay V, Lee C, Vaishampayan U, Miller W, Bhagavatheeswaran P, Wang Y, Gupta S, DeSilva H, Lee C, Escudier B, Motzer R. Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial. ESMO Open 2024, 9: 104073. PMID: 39642635, PMCID: PMC11667034, DOI: 10.1016/j.esmoop.2024.104073.Peer-Reviewed Original ResearchConceptsAdvanced renal cell carcinomaNivolumab + ipilimumabProgression-free survivalDuration of responseMedian duration of responseProgression-free survival ratesProgrammed death-ligand 1Renal cell carcinomaImmuno-oncologyOpen-labelCell carcinomaPatients treated with nivolumabTyrosine kinase inhibitor therapyTreatment-related adverse eventsLymphocyte activation gene-3Death-ligand 1Kinase inhibitor therapyAssessment of combination therapyEffective combination regimenImmuno-oncology studiesCombination regimenInhibitor therapyLAG-3Combination therapySecondary endpointsCirculating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma
Lu B, Lucca L, Lewis W, Wang J, Nogueira C, Heer S, Rayon-Estrada V, Axisa P, Reeves S, Buitrago-Pocasangre N, Pham G, Kojima M, Wei W, Aizenbud L, Bacchiocchi A, Zhang L, Walewski J, Chiang V, Olino K, Clune J, Halaban R, Kluger Y, Coyle A, Kisielow J, Obermair F, Kluger H, Hafler D. Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma. Nature Immunology 2024, 26: 82-91. PMID: 39609626, DOI: 10.1038/s41590-024-02023-4.Peer-Reviewed Original ResearchCD8+ T cellsAnti-tumor immunityRegulatory T cellsT cellsSubpopulation of CD8+ T cellsCytotoxic CD8+ T cellsHuman CD8+ T cellsTumor antigen-specific CD8Impaired anti-tumor immunityTumor antigen-specificPoor overall survivalTumor rejectionKIR expressionOverall survivalTumor antigensImmune evasionCellular mediatorsHuman cancersCD8MelanomaTumorTranscriptional programsFunctional heterogeneityImmunityPatientsDecoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma
Schoenfeld D, Djureinovic D, Su D, Zhang L, Lu B, Kamga L, Mann J, Huck J, Hurwitz M, Braun D, Jilaveanu L, Ring A, Kluger H. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma. JCI Insight 2024, 10: e184545. PMID: 39561007, PMCID: PMC11721305, DOI: 10.1172/jci.insight.184545.Peer-Reviewed Original ResearchAnti-CTLA-4Renal cell carcinomaIL-18IL-18BPCell carcinomaTumor microenvironmentTumor typesPatients treated with immune checkpoint inhibitorsRegulatory T cell levelsAnti-PD-1 treatmentCD8+ T cellsAnti-PD-1Immune checkpoint inhibitorsCell renal cell carcinomaNon-responder patientsMyeloid cell populationsT cell levelsCytokine interleukin-18Anti-cancer efficacySecreted binding proteinCheckpoint inhibitorsResponding patientsPreclinical modelsT cellsMurine model16S rRNA target sequencing of human tumors validates findings of Lachnoclostridium abundance in human melanomas that are heavily CD8+ T-cell infiltrated
Lu L, Johnson C, Khan S, Kluger H. 16S rRNA target sequencing of human tumors validates findings of Lachnoclostridium abundance in human melanomas that are heavily CD8+ T-cell infiltrated. European Journal Of Cancer 2024, 213: 115084. PMID: 39477777, DOI: 10.1016/j.ejca.2024.115084.Peer-Reviewed Original Research1102P Immune checkpoint inhibitor rechallenge after treatment with tumor-infiltrating lymphocytes in unresectable melanoma
Warner A, Smithy J, Los C, Kalvin H, Hasson N, Amaria R, Czapla J, Schollenberger M, furness A, Hassel J, Wermke M, Gallegos J, Lutzky J, Lipson E, Sullivan R, Kluger H, Panageas K, Klobuch S, Haanen J, Shoushtari A. 1102P Immune checkpoint inhibitor rechallenge after treatment with tumor-infiltrating lymphocytes in unresectable melanoma. Annals Of Oncology 2024, 35: s730-s731. DOI: 10.1016/j.annonc.2024.08.1170.Peer-Reviewed Original ResearchTIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3
Perales O, Jilaveanu L, Adeniran A, Su D, Hurwitz M, Braun D, Kluger H, Schoenfeld D. TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3. Cancer Immunology, Immunotherapy 2024, 73: 192. PMID: 39105820, PMCID: PMC11303630, DOI: 10.1007/s00262-024-03773-8.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaRenal cell carcinoma tumorsT cellsTIGIT expressionCheckpoint inhibitorsPD-1Likelihood of response to therapyTumor-infiltrating T cellsCD3+ T cellsRenal cell carcinoma metastasisTreatment of renal cell carcinomaImmune checkpoint inhibitorsInfiltrating T cellsPurposeImmune checkpoint inhibitorsResponse to therapyT cell immunoglobulinCD3+ levelsMetastatic RCC specimensAdjacent normal renal tissuesNormal renal tissuesQuantitative immunofluorescence analysisCell carcinomaResistant diseasePotential therapeutic targetTissue microarrayGP100 expression is variable in intensity in melanoma
Mann J, Hasson N, Su D, Adeniran A, Smalley K, Djureinovic D, Jilaveanu L, Schoenfeld D, Kluger H. GP100 expression is variable in intensity in melanoma. Cancer Immunology, Immunotherapy 2024, 73: 191. PMID: 39105816, PMCID: PMC11303354, DOI: 10.1007/s00262-024-03776-5.Peer-Reviewed Original ResearchConceptsGp100 expressionCutaneous melanomaTreatment of cutaneous melanomaAdvanced cutaneous melanomaT-cell engagersImprove patient selectionMetastatic melanomaUveal melanomaMetastatic samplesPatient selectionClinical trialsMelanomaQuantitative immunofluorescence methodGp100Improve outcomesImmunofluorescence methodTherapeutic intentDrugCellular productsExpressionTebentafuspImmunohistochemistry
Clinical Trials
Current Trials
Melanoma Margins Trial-II - A Phase III, Multi-centre Randomised Controlled Trial Investigating 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma (02.18 MelMarT-II)
HIC ID2000033087RoleSub InvestigatorPrimary Completion Date12/31/2029Recruiting ParticipantsImpact of cancer immunotherapy on the kidneys
HIC ID2000033212RoleSub InvestigatorPrimary Completion Date07/31/2032Recruiting ParticipantsA Phase 1a Open-Label, Dose-Escalation, and a Phase 2 Study to Investigate the Safety, PK, PD, and Clinical Activity of ST-067 Administered Subcutaneously as Monotherapy in Patients With Relapsed or Refractory Solid Tumors
HIC ID2000030299RolePrincipal InvestigatorPrimary Completion Date06/30/2025Recruiting ParticipantsA Phase 1/2, First-In-Human, Multi-Part, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF6002 as a Monotherapy and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications
HIC ID2000029137RoleSub InvestigatorPrimary Completion Date07/19/2024Recruiting ParticipantsPhase 2 Trial of Voyager V1 in Combination With Cemiplimab in Patients With Hepatocellular Carcinoma, Non-Small Cell Lung Cancer, Melanoma or Endometrial Carcinoma
HIC ID2000027272RoleSub InvestigatorPrimary Completion Date03/01/2024Recruiting Participants
Clinical Care
Overview
Dr. Kluger is a medical oncologist who sees patients with melanoma and renal cell carcinoma. Her research interests focus on developing new drug regimens and biomarkers predictive of response to therapies in melanoma and renal cell carcinoma. She participates in a number of clinical trials studying new agents for the treatment of these diseases, both targeting the immune system and the cancer cell. She runs an active research laboratory that studies tumor and immune cells from patients treated with novel therapies to determine mechanisms of resistance to therapy and mediators of toxicity from immune checkpoint inhibitors. The laboratory also conducts pre-clinical studies to improve treatment regimens for patients with melanoma, renal cell carcinoma or brain metastasis.
Clinical Specialties
Medical Oncology; Hematology & Oncology; Melanoma and Onco-Dermatology; Genitourinary Oncology
Fact Sheets
Merkel Cell Carcinoma (MCC)
Learn More on Yale MedicineMetastatic Cancer
Learn More on Yale MedicineMelanoma
Learn More on Yale MedicineSkin Cancer
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Yale Medicine News
News & Links
News
- February 26, 2025
Celebrating Yale Cancer Center Faculty, Research Scientists
- January 01, 2025Source: AACR Cancer Progress Report
Jennifer Ficko: Thriving Thanks to a Melanoma Clinical Trial
- December 31, 2024
Accolades, Awards & Honors
- November 28, 2024
Unexpected Findings in Study of T Cells, Considered Front-line Fighters Against Advanced Melanoma
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Apr 202528Monday
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May 202526Monday
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