2024
First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors
Shimizu T, Powderly J, Razak A, LoRusso P, Miller K, Kao S, Kongpachith S, Tribouley C, Graham M, Stoll B, Patel M, Sahtout M, Blaney M, Leibman R, Golan T, Tolcher A. First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors. Frontiers In Oncology 2024, 14: 1376551. DOI: 10.3389/fonc.2024.1376551.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-escalation phaseDose escalationSolid tumorsSurface of regulatory T cellsRecommended phase 2 doseSuppress antitumor immune responsesCombination therapy cohortsDose-proportional PKMonotherapy-treated patientsPhase 2 doseMedian response durationAntitumor immune responseDose-limiting toxicityTherapy-treated patientsRegulatory T cellsMaximum administered doseFirst-in-humanDose escalation resultsGlycoprotein A repetitionsPromote tumor growthBlood biomarker dataDose expansionPretreated patientsEscalating doses
2023
Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors
Kim T, Bedard P, LoRusso P, Gordon M, Bendell J, Oh D, Ahn M, Garralda E, D’Angelo S, Desai J, Hodi F, Wainberg Z, Delord J, Cassier P, Cervantes A, Gil-Martin M, Wu B, Patil N, Jin Y, Hoang T, Mendus D, Wen X, Meng R, Cho B. Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors. JAMA Oncology 2023, 9: 1574-1582. PMID: 37768658, PMCID: PMC10540058, DOI: 10.1001/jamaoncol.2023.3867.Peer-Reviewed Original ResearchConceptsObjective response rateAdvanced solid tumorsAdverse eventsPhase 1bAntitumor activityCancer cohortNon-small cell lung cancer (NSCLC) cohortFrequent treatment-related adverse eventsInvestigator-assessed objective response rateSolid tumorsCell lung cancer cohortTreatment-related adverse eventsMajority of AEsEnd pointClinical cutoff dateDose-escalation cohortsDose-expansion cohortsEsophageal cancer cohortPhase 2 dosePrior cancer therapyPrimary end pointSecondary end pointsHalf of patientsNew safety signalsAntitumor immune response
2022
732MO The combination of ICT01, a γ9δ2 T cell-activating mAb, plus pembrolizumab induces a broad antitumor immune response and disease control in patients with CPI-failure melanoma, NSCLC and bladder cancer: EVICTION trial
Champiat S, Wermke M, Vicier C, de Bono J, Jungels C, Vey N, Kotecki N, Wetzko K, Ruhnke L, Garralda E, de Aguiar V, Lorusso P, de Gassart A, Valentin E, Brune P, Iche M, Leparquier C, Olive D, Marabelle A, Frohna P. 732MO The combination of ICT01, a γ9δ2 T cell-activating mAb, plus pembrolizumab induces a broad antitumor immune response and disease control in patients with CPI-failure melanoma, NSCLC and bladder cancer: EVICTION trial. Annals Of Oncology 2022, 33: s877-s878. DOI: 10.1016/j.annonc.2022.07.858.Peer-Reviewed Original Research
2021
503 Clinical activity of ICT01, an anti-BTN3A-targeted, γ9δ2-activating mAb, alone and in combination with pembrolizumab in patients with advanced/refractory solid tumors: EVICTION trial
Wermke M, Marabelle A, Jungels C, Bono J, Vey N, Vicier C, Garralda E, Gouill S, LoRusso P, Champiat S, List C, Aguiar V, Wetzko K, Rhunke L, Gassart A, Brune P, Valentin E, Iche M, Olive D, Frohna P. 503 Clinical activity of ICT01, an anti-BTN3A-targeted, γ9δ2-activating mAb, alone and in combination with pembrolizumab in patients with advanced/refractory solid tumors: EVICTION trial. 2021, a535-a535. DOI: 10.1136/jitc-2021-sitc2021.503.Peer-Reviewed Original ResearchΓ9δ2 T cellsCD8 T cellsRefractory solid tumorsSolid tumor patientsT cellsSolid tumorsTumor patientsBroad antitumor immune responseHospital Universitari Vall d’HebronEthics CommitteeT-cell countsAntitumor immune responseTumor-infiltrating lymphocytesNK cell activationPreliminary efficacy dataInstitut Jules BordetDose-dependent increaseSubsequent clinical benefitCytokine level analysisCommon AEsDose cohortsEudraCT numberLow TILsPhase 1/2aSerum cytokines516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial
Aix S, Calvo E, Moreno V, Garralda E, Cervantes A, Ramalingam S, Pérez J, LoRusso P, Furqan M, Cho D, Muik A, Lagkadinou E, Türeci Ö, Couto S, Pencheva N, Forssmann U, Şahin U, Ahmadi T, Higgs B, Jure-Kunkel M, Melero I. 516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial. Journal For ImmunoTherapy Of Cancer 2021, 9: a546-a546. DOI: 10.1136/jitc-2021-sitc2021.516.Peer-Reviewed Original ResearchPrior anti-PD-1 therapyAnti-PD-1 therapyPD-L1NK cellsTumor reductionAnti-PD-1 combination therapyEffector memory T cellsPD-L1 blockadePhase 1/2a trialPrior systemic therapySoluble immune mediatorsTumor PD-L1Disease control rateAdvanced solid tumorsAntitumor immune responseSubset of patientsMemory T cellsSerial blood samplesImproved clinical efficacyTumor biopsy specimensCycle 1Tumor biopsy samplesEthics committees/institutional review boardsInstitutional review boardCycle 2
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