Sarah Weiss, MD
Assistant Professor AdjunctCards
About
Research
Overview
Dr. Weiss joined the Melanoma and Renal Cell Carcinoma Disease Aligned Research Team at Yale in August 2016 and has a growing clinical practice. Her primary research interests are to develop innovative clinical trials for the management of advanced melanoma, and to identify and integrate prognostic and predictive biomarkers into clinical practice. She is currently the site Principal Investigator on several clinical trials including a study of Apexigen’s CD40 agonist in combination with nivolumab in patients with melanoma who are resistant to PD-1 immune checkpoint inhibitors. This has led to an investigator-initiated clinical trial protocol that Dr. Weiss wrote based off of preclinical work conducted in the Kaech and Bosenberg laboratories here at Yale, aimed at overcoming resistance to PD-1/PD-L1 agents by targeting both the innate and adaptive immune systems with a triple combination of a CD40 agonist, CSF1R inhibitor, and PD-1 inhibitor.
Medical Research Interests
Immunotherapy; Melanoma
Public Health Interests
Cancer
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 progressionMelanomaPatients
2024
Patterns of brain metastases response to immunotherapy with pembrolizumab
Mahajan A, Goldberg S, Weiss S, Tran T, Singh K, Joshi K, Aboian M, Kluger H, Chiang V. Patterns of brain metastases response to immunotherapy with pembrolizumab. Journal Of Neuro-Oncology 2024, 169: 555-561. PMID: 38963658, DOI: 10.1007/s11060-024-04754-8.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metastasesComplete resolutionLung cancerMedian time to CNS progressionLesion progressionNon-small cell lung cancer patientsModified RECIST criteriaPD-1 inhibitorsTrial of pembrolizumabEffective systemic treatmentResponse to immunotherapyPhase II trialCell lung cancerMethodsThis retrospective studyLocal treatment decisionsPurposeCentral nervous systemCNS progressionRECIST criteriaPD-1Local therapySystemic treatmentMRI evaluationResponse assessmentRetrospective study
2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysisUse of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies
Ji S, Liu H, Pachella L, Stephenson R, Groisberg R, Weiss S. Use of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies. Frontiers In Transplantation 2023, 2: 1284740. PMID: 38993910, PMCID: PMC11235332, DOI: 10.3389/frtra.2023.1284740.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsCutaneous squamous cell carcinomaObjective response rateMerkel cell carcinomaSolid organ transplant recipientsOrgan transplant recipientsSOT recipientsGraft rejectionCutaneous malignanciesCheckpoint inhibitorsTransplant recipientsCell carcinomaRetrospective analysisFirst-line immune checkpoint inhibitorsPrior systemic therapyAdvanced skin cancerSquamous cell carcinomaAdvanced cutaneous malignanciesImmunosuppressive therapyAllograft rejectionGraft failureSystemic therapyAdvanced melanomaCare therapyImmunosuppressive agentsSociety for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0
Pavlick A, Ariyan C, Buchbinder E, Davar D, Gibney G, Hamid O, Hieken T, Izar B, Johnson D, Kulkarni R, Luke J, Mitchell T, Mooradian M, Rubin K, Salama A, Shirai K, Taube J, Tawbi H, Tolley J, Valdueza C, Weiss S, Wong M, Sullivan R. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0. Journal For ImmunoTherapy Of Cancer 2023, 11: e006947. PMID: 37852736, PMCID: PMC10603365, DOI: 10.1136/jitc-2023-006947.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsClinical practice guidelinesCutaneous melanomaTreatment of melanomaPractice guidelinesProlongs recurrence-free survivalCancer clinical practice guidelinesCell death protein 1Metastatic cutaneous melanomaBispecific T cell engager (BiTE) therapyChemotherapy-resistant diseaseRecurrence-free survivalDeath protein 1Long-term followManagement of patientsSpecial patient populationsImmunotherapy of cancerConsensus-based recommendationsPossibility of cureUnique toxicity profileQuality of lifeIntratumoral immunotherapyNeoadjuvant strategiesAdvanced diseaseBrain metastasesA Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1
Weiss S, Sznol M, Shaheen M, Berciano-Guerrero M, Couselo E, Rodríguez-Abreu D, Boni V, Schuchter L, Gonzalez-Cao M, Arance A, Wei W, Ganti A, Hauke R, Berrocal A, Iannotti N, Hsu F, Kluger H. A Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1. Clinical Cancer Research 2023, 30: 74-81. PMID: 37535056, PMCID: PMC10767304, DOI: 10.1158/1078-0432.ccr-23-0475.Peer-Reviewed Original ResearchConceptsObjective response ratePhase II trialAdverse eventsPartial responseDisease progressionII trialGrade 3 adverse eventsAnti PD-1CD40 agonist antibodyElevated liver functionTreatment-related SAEsCommon adverse eventsActivation of CD40Subset of patientsFavorable safety profileAntigen presenting cellsStable diseaseMedian durationAdvanced melanomaAdditional patientsLiver functionSafety profileMetastatic melanomaPreclinical dataPresenting cellsCheckMate-915: does adjuvant CTLA-4 blockade play a role in resected melanoma?
Su D, Kluger H, Weiss S. CheckMate-915: does adjuvant CTLA-4 blockade play a role in resected melanoma? Annals Of Translational Medicine 2023, 0: 0-0. PMID: 37675335, PMCID: PMC10477634, DOI: 10.21037/atm-23-754.Peer-Reviewed Original ResearchCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeCase report: Metastatic Merkel cell carcinoma presenting seven years after loco-regional disease resection of primary tumor with interval in-transit and nodal metastases
Rusheen J, Clune J, Ariyan S, Baumann R, Kluger H, Olino K, Weiss S. Case report: Metastatic Merkel cell carcinoma presenting seven years after loco-regional disease resection of primary tumor with interval in-transit and nodal metastases. Frontiers In Oncology 2023, 13: 1217816. PMID: 37476373, PMCID: PMC10354444, DOI: 10.3389/fonc.2023.1217816.Peer-Reviewed Case Reports and Technical NotesMerkel cell carcinomaDuration of surveillanceLate recurrenceCell carcinomaMetastatic Merkel cell carcinomaPrimary Merkel cell carcinomaMetastases 15 monthsSuch late recurrencesPredictors of recurrenceNodal recurrenceDefinitive therapyFirst recurrenceDisease resectionNodal metastasisPhysical examinationRare tumorPrimary diagnosisPrimary tumorRisk factorsHigh riskNational guidelinesRecurrenceOptimal durationPatientsCarcinoma
News
News
- October 23, 2023
Rare Case of Late-recurring Merkel Cell Carcinoma
- January 13, 2021
Discoveries & Impact (January 2021)
- September 27, 2019Source: CT Insider
Perspectives: Stand up to the challenges of cancer to preserve life
- February 03, 2019
Meet Yale Internal Medicine: Q&A with Sarah Weiss, MD, Assistant Professor of Medicine (Medical Oncology)