2022
Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer.
Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Stadler Z, Yaeger R, Smith J, Saltz L, El Dika I, Crane C, Romesser P, Iyer K, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser M, Schalper K, Diaz L. Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer. Journal Of Clinical Oncology 2022, 40: lba5-lba5. DOI: 10.1200/jco.2022.40.17_suppl.lba5.Peer-Reviewed Original ResearchPD-1 blockadeAdvanced rectal cancerSingle-agent PD-1 blockadeClinical complete responseRectal cancerCo-primary endpointsComplete responseAnti-PD-1 monoclonal antibodyProspective phase II studyPD-1 monoclonal antibodyMismatch repair-deficient colorectal cancersCurative-intent treatmentPhase II studySerious adverse eventsCase of progressionEvidence of tumorDigital rectal examDeficient colorectal cancerMetastatic settingNeoadjuvant chemotherapyAdverse eventsCheckpoint blockadeII studySurgical resectionRectal adenocarcinoma
2020
Trial in progress: A phase II open-label, randomized study of PARP inhibition (olaparib) either alone or in combination with anti-PD-L1 therapy (atezolizumab) in homologous DNA repair (HDR) deficient, locally advanced or metastatic non-HER2-positive breast cancer.
LoRusso P, Pilat M, Santa-Maria C, Connolly R, Roesch E, Afghahi A, Han H, Nanda R, Wulf G, Assad H, Park H, Dees E, Force J, Noonan A, Brufsky A, Abramson V, Haley B, Buys S, Sharon E, Schalper K. Trial in progress: A phase II open-label, randomized study of PARP inhibition (olaparib) either alone or in combination with anti-PD-L1 therapy (atezolizumab) in homologous DNA repair (HDR) deficient, locally advanced or metastatic non-HER2-positive breast cancer. Journal Of Clinical Oncology 2020, 38: tps1102-tps1102. DOI: 10.1200/jco.2020.38.15_suppl.tps1102.Peer-Reviewed Original ResearchPositive breast cancerPo bidPARP inhibitionBreast cancerImmune responseOpen-label phase II clinical trialAdaptive anti-tumor immune responsesAnti-tumor immune responsePhase II clinical trialMarked lymphocyte infiltrationPD-1 blockadePD-L1 expressionPre-treatment biopsiesProgression-free survivalAntitumor immune responseImmune checkpoint blockadeMajority of patientsBRCA 1/2 mutationsTumor immune contextureBiopsy time pointsHomologous DNA repairPARP inhibitor olaparibMonotherapy armCombination armImmune contexture
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutations