2022
A phase 1b, multicenter, dose-escalation study of subasumstat (TAK-981) in combination with pembrolizumab in patients (pts) with advanced solid tumors.
Goel S, Ulahannan S, Olszanski A, LoRusso P, Sanborn R, Sharma S, Emens L, Reilley M, Priego V, Li S, Wang B, Dong L, Sachsenmeier K, Gibbs J, Gharavi R, Martinez A, Proscurshim I, Fram R, Gomez-Pinillos A, Rasco D. A phase 1b, multicenter, dose-escalation study of subasumstat (TAK-981) in combination with pembrolizumab in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 2506-2506. DOI: 10.1200/jco.2022.40.16_suppl.2506.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsCheckpoint inhibitorsDay 1Anti-PD-1 checkpoint inhibitorsMicrosatellite stable colorectal cancerSynergistic tumor growth inhibitionDose-escalation partPhase 1b studyPhase 2 dosePre-treated NSCLCPromising anti-tumor activityRelapsed/refractoryT cell-dependent antitumor responseAdvanced solid tumorsDose-escalation studyActivation of CD8Dose-limiting toxicityNatural killer cellsCell lung cancerFavorable safety profilePhase 2 clinical developmentSyngeneic mouse modelDependent immune responsesType 1 interferonAnti-tumor activityPhase 1b study of the novel first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-relapsed and refractory solid malignancies and dose escalation update.
Muller C, Chaney M, Cohen J, Garyantes T, Lin J, LoRusso P, Mita A, Mita M, Natale C, Orloff M, Papadopoulos K, Patel S, Ahnert J. Phase 1b study of the novel first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in combination with pembrolizumab in patients with immune checkpoint inhibitor (ICI)-relapsed and refractory solid malignancies and dose escalation update. Journal Of Clinical Oncology 2022, 40: 2574-2574. DOI: 10.1200/jco.2022.40.16_suppl.2574.Peer-Reviewed Original ResearchG protein-coupled estrogen receptorFavorable safety profileStable diseaseLong-term benefitsHuman dose-escalation studyProtein-coupled estrogen receptorMetastatic uveal melanoma patientsEncouraging anti-tumor activityClinical benefit rateDose-escalation portionPhase 1b studyRefractory solid malignanciesImmune checkpoint inhibitorsObjective response rateDose-escalation studyMetastatic solid tumorsUveal melanoma patientsDuration of treatmentAnti-tumor activityEstrogen receptor agonistsSmall molecule agonistsCTCAE v5.0Evaluable patientsMeasurable diseaseRECIST v1.1First in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response
Yap TA, Gainor JF, Callahan MK, Falchook GS, Pachynski RK, LoRusso P, Kummar S, Gibney GT, Burris HA, Tykodi SS, Rahma OE, Seiwert TY, Papadopoulos KP, Murphy M, Park H, Hanson A, Hashambhoy-Ramsay Y, McGrath L, Hooper E, Xiao X, Cohen H, Fan M, Felitsky D, Hart C, McComb R, Brown K, Sepahi A, Jimenez J, Zhang W, Baeck J, Laken H, Murray R, Trehu E, Harvey CJ. First in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response. Clinical Cancer Research 2022, 28: 3695-3708. PMID: 35511938, PMCID: PMC9433959, DOI: 10.1158/1078-0432.ccr-21-4256.Peer-Reviewed Original ResearchConceptsSubset of patientsPredictive biomarkersPharmacodynamic biomarkersModest objective response rateNon-small cell lung cancer trialsCD4 T cell populationCell lung cancer trialsPhase IObjective response ratePhase II doseAdvanced solid tumorsCD4 T cellsFavorable safety profilePotential predictive biomarkersLung cancer trialsPredictors of responseT cell populationsGreater clinical benefitClinical outcomesClinical benefitSafety profileCancer trialsNivolumabT cellsPatients
2021
498 Evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) and with gastric/gastroesophageal cancer (GC); ASPEN-01
Lee K, Chung H, Kim T, Lakhani N, Messersmith W, Santana-Davila R, Kim W, LoRusso P, Bang Y, Chow L, Fanning P, Squifflet P, Jin F, Forgie A, Wan H, Pons J, Randolph S, Gainor J. 498 Evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) and with gastric/gastroesophageal cancer (GC); ASPEN-01. Journal For ImmunoTherapy Of Cancer 2021, 9: a530-a530. DOI: 10.1136/jitc-2021-sitc2021.498.Peer-Reviewed Original ResearchTreatment-related AEsGastroesophageal cancerCheckpoint inhibitorsAdvanced HNSCCEvaluable patientsHER2-positive gastroesophageal cancerNeck squamous cell carcinomaCytotoxic chemotherapy regimensLong-term PFSGastroesophageal junction cancerPhase 1 studyFavorable safety profileHER2-positive advanced gastricSquamous cell carcinomaAdaptive antitumor immunityWarrants further evaluationChemotherapy regimensPrimary endpointAdvanced gastricAdvanced malignanciesJunction cancerLine therapyMethods PatientsStandard chemotherapyAntitumor immunity493 First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4–1BB (GEN1042) in patients with advanced solid tumors
Johnson M, Lopez J, LoRusso P, Bauman J, Haggstrom D, Lagkadinou E, Bajaj G, Türeci Ö, Adams H, Şahin U, Fu Y, Ahmadi T, Rohrberg K. 493 First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4–1BB (GEN1042) in patients with advanced solid tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a525-a525. DOI: 10.1136/jitc-2021-sitc2021.493.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-limiting toxicityAdverse eventsSolid tumorsPartial responseLung cancerAntitumor activityNon-CNS solid tumorsTreatment-related adverse eventsEffector memory T cellsDrug-related gradeInitial clinical activityPD-1 inhibitorsPhase 1/2 trialTumor-specific immunityMemory T cellsCell lung cancerFavorable safety profilePreliminary antitumor activityNeuroendocrine lung cancerBest overall responseEnd of infusionCommon cancer typesEthics committees/institutional review boardsInstitutional review board
2019
Phase 1a/1b study of first-in-class B7-H4 antibody, FPA150, as monotherapy in patients with advanced solid tumors.
Sachdev J, Bauer T, Chawla S, Pant S, Patnaik A, Wainberg Z, Inamdar S, Marina N, Sun S, Schmidt M, Xiang H, LoRusso P. Phase 1a/1b study of first-in-class B7-H4 antibody, FPA150, as monotherapy in patients with advanced solid tumors. Journal Of Clinical Oncology 2019, 37: 2529-2529. DOI: 10.1200/jco.2019.37.15_suppl.2529.Peer-Reviewed Original ResearchTreatment-related AEsAdvanced solid tumorsB7-H4Solid tumorsExploration cohortEndometrial cancerDose escalationTreatment-related serious adverse eventsAntibody-dependent cell-mediated cytotoxicityB7-H4 antibodyDose-proportional exposureSerious adverse eventsT cell activityCell-mediated cytotoxicityFavorable safety profileT cell functionAnti-tumor activityPreliminary biomarkerPrior therapyTreatment biopsiesAdverse eventsMost patientsSafety profileB7 familyEfficacy data
2016
Antibody–Drug Conjugates (ADCs) in Clinical Development
McLaughlin J, LoRusso P. Antibody–Drug Conjugates (ADCs) in Clinical Development. 2016, 321-344. DOI: 10.1002/9781119060727.ch13.Peer-Reviewed Original ResearchAntibody-drug conjugatesCytotoxic agentsMonoclonal antibodiesLocal immune responseFavorable safety profileConventional cytotoxic chemotherapyConventional cytotoxic agentsDifferent antibody–drug conjugatesImmune-stimulating agentsAnti-neoplastic agentsCytotoxic chemotherapySafety profileCancer patientsIL-2Clinical trialsImmune responseClinical developmentOncologist's abilityImproved efficacyPhase IDrug conjugatesAntibodiesEfficacyTarget effectsToxicity
2012
Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy.
Alsina M, Tabernero J, Shapiro G, Burris H, Infante J, Weiss G, Cervantes-Ruiperez A, Gounder M, Paz-Ares L, Falzone R, Hill J, Cehelsky J, Vaishnaw A, Gollob J, LoRusso P. Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy. Journal Of Clinical Oncology 2012, 30: 3062-3062. DOI: 10.1200/jco.2012.30.15_suppl.3062.Peer-Reviewed Original ResearchStable diseasePartial responseExtension studyAdverse eventsEndometrial cancerCancer patientsCell carcinomaOpen-label extension studyNeck squamous cell carcinomaMore prior therapiesOngoing partial responseSafety/tolerabilityUnconfirmed partial responseEndometrial cancer patientsPhase II trialMonths of treatmentPhase I trialPhase 1 trialFavorable safety profileSquamous cell carcinomaTime of enrollmentPancreatic neuroendocrine tumorsVascular endothelial growth factorYears of treatmentRenal cell carcinoma