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. PMID: 39534099, PMCID: PMC11555770, 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 dosesA phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation.
Heumann T, Stockton S, Cecchini M, Aljumaily R, Shyr C, Whisenant J, Starr J, Dayyani F, Baranda J, Trikalinos N, Ivy S, LoRusso P, Das S, Gore S, Beumer J, Berlin J. A phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation. Journal Of Clinical Oncology 2024, 42: 3077-3077. DOI: 10.1200/jco.2024.42.16_suppl.3077.Peer-Reviewed Original ResearchAdvanced solid tumorsMaximum tolerated doseDose escalationSolid tumorsPhase I study of irinotecanRecommended phase 2 doseRefractory advanced solid tumorsPhase 2 dosePhase I studyAnti-tumor activityBiweekly irinotecanInhibitor irinotecanIrinotecan exposureWeekly irinotecanTolerated doseDosing scheduleCancer xenograftsAdult patientsIrinotecanAssess safetyATR inhibitorsElimusertibSecondary objectivesDoseStandard careA phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation.
Stockton S, Shyr C, Cecchini M, Aljumaily R, Halfdanarson T, Sonbol M, Whisenant J, Ivy S, LoRusso P, Das S, Gore S, Berlin J, Beumer J, Heumann T. A phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation. Journal Of Clinical Oncology 2024, 42: 3076-3076. DOI: 10.1200/jco.2024.42.16_suppl.3076.Peer-Reviewed Original ResearchMaximum tolerated doseDose escalationDose levelsMedian progression-free survivalRecommended phase 2 doseRefractory advanced solid tumorsResults of dose escalationTreatment-related adverse eventsSmall cell lung cancerDisease control ratePhase 2 dosePhase Ia studyDose-limiting toxicityProgression-free survivalAdvanced solid tumorsPhase I studyCell lung cancerAnti-tumor activityExpansion cohortPartial responseTolerated doseTopotecan exposureStudy drugCancer xenograftsRespiratory failure
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 responseMirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose expansion results.
Carneiro B, Perets R, Dowlati A, LoRusso P, Yonemori K, He L, Munasinghe W, Noorani B, Johnson E, Zugazagoitia J. Mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose expansion results. Journal Of Clinical Oncology 2023, 41: 3027-3027. DOI: 10.1200/jco.2023.41.16_suppl.3027.Peer-Reviewed Original ResearchNon-small cell lung cancerSmall cell lung cancerOverall response rateCommon adverse eventsRefractory solid tumorsCell lung cancerSCLC cohortBest overall responseAdverse eventsMonotherapy cohortTaxane therapyLung cancerSolid tumorsConfirmed overall response rateDose-expansion phaseOngoing phase 1Phase 2 dosePrior taxane therapyTolerable safety profileDisease control rateGrade 3/4 neutropeniaOpen-label studyDose-escalation phasePhase 1 studySingle-agent activityTrial in progress: A phase 1, first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of ASP3082 in patients with previously treated advanced solid tumors and KRAS G12D mutations.
Tolcher A, Park W, Wang J, Spira A, Janne P, Lee H, Gill S, LoRusso P, Herzberg B, Goldman J, Morgensztern D, Berlin J, Kasi A, Fujii H, Pelster M. Trial in progress: A phase 1, first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of ASP3082 in patients with previously treated advanced solid tumors and KRAS G12D mutations. Journal Of Clinical Oncology 2023, 41: tps764-tps764. DOI: 10.1200/jco.2023.41.4_suppl.tps764.Peer-Reviewed Original ResearchKRAS G12DAdverse eventsLung cancerKRAS G12D mutationCancer cellsEastern Cooperative Oncology Group performance statusSolid tumorsNon-small cell lung cancerMetastatic solid tumor malignanciesSolid Tumors version 1.1Dose-escalation cohortsDose-expansion studyPhase 2 doseDisease control rateObjective response rateSerious adverse eventsAdvanced solid tumorsResponse Evaluation CriteriaDose-limiting toxicityPancreatic ductal cancerPhase 1 studyCell lung cancerDuration of responseSolid tumor malignanciesG12D mutation
2022
A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance.
Yap T, LoRusso P, Wong D, Hu-Lieskovan S, Papadopoulos K, Holz J, Grabowska U, Gradinaru C, Leung K, Marshall S, Reader C, Russell R, Sainson R, Seal C, Shepherd C, Germaschewski F, Gliddon D, Stern O, Young L, Brewis N, Kayitalire L, Morrow M. A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance. Clinical Cancer Research 2022, 29: 888-898. PMID: 36342102, DOI: 10.1158/1078-0432.ccr-22-1449.Peer-Reviewed Original ResearchConceptsDisease control rateLAG-3PD-L1Advanced cancerOverall disease control rateDisease controlPeripheral effector cellsPhase 2 doseSerious adverse eventsPhase 1 studySoluble LAG-3Tetravalent bispecific antibodyPrior regimensStable diseaseDose expansionMetastatic settingAdverse eventsPartial responseEffector cellsClinical benefitControl rateSustained elevationTitration designPharmacodynamic activityHuman studiesInterim safety and efficacy results from AURELIO-03: A phase 1 dose escalation study of the IL-2/IL-15 receptor βγ superagonist SOT101 as a single agent and in combination with pembrolizumab in patients with advanced solid tumors.
Garralda E, Naing A, Galvao V, LoRusso P, Grell P, Cassier P, Gomez-Roca C, Korakis I, Bechard D, Jelinkova L, Adkins I, Tillmanns S, Kiemle-Kallee J, Marabelle A, Champiat S. Interim safety and efficacy results from AURELIO-03: A phase 1 dose escalation study of the IL-2/IL-15 receptor βγ superagonist SOT101 as a single agent and in combination with pembrolizumab in patients with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 2502-2502. DOI: 10.1200/jco.2022.40.16_suppl.2502.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsClinical benefit rateAdvanced solid tumorsPartial responseStable diseaseMedian durationComplete responseClinical benefitBenefit rateAnti-programmed cell death protein 1 antibodyCommon treatment-emergent adverse eventsSolid tumorsMost treatment-emergent adverse eventsPhase 1 dose-escalation studyCell death protein 1 antibodyIL-15 receptor αSkin squamous cell carcinomaIL-2/ILFirst tumor assessmentOngoing complete responsePhase 2 dosePromising efficacy signalsTreatment-related deathsDose-escalation studyPhase 1 studyPhase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER).
Falchook G, Ribas A, Davar D, Eroglu Z, Wang J, Luke J, Hamilton E, Di Pace B, Wang T, Ghosh S, Dhar A, Borgovan T, Waszak A, LoRusso P. Phase 1 trial of TIM-3 inhibitor cobolimab monotherapy and in combination with PD-1 inhibitors nivolumab or dostarlimab (AMBER). Journal Of Clinical Oncology 2022, 40: 2504-2504. DOI: 10.1200/jco.2022.40.16_suppl.2504.Peer-Reviewed Original ResearchTreatment-related treatment-emergent adverse eventsNon-small cell lung cancerPD-1 inhibitor nivolumabTreatment-emergent adverse eventsTumor-infiltrating T cellsPreliminary anti-tumor activityPhase 2 doseOpen-label studyPD-1 inhibitorsAdvanced solid tumorsPhase 2 studyDose-proportional mannerPhase 1 trialT cell suppressionCell lung cancerTherapeutic dose rangeMost common cancersAnti-tumor activityDose delaysPrior therapyInhibitor nivolumabPrimary endpointTim-3Adverse eventsPeritoneal mesotheliomaA 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 activityA first-in-human, phase 1 study of ASTX029, a dual-mechanism inhibitor of ERK1/2, in relapsed/refractory solid tumors.
LoRusso P, Rasco D, Shapiro G, Mita A, Azad N, Swiecicki P, El-Khoueiry A, Gandara D, Kummar S, Tanajian H, Taylor J, Bottone F, Toguchi M, Hindley C, Chan D, Oganesian A, Keer H, Dao K, Sullivan R, Spira A. A first-in-human, phase 1 study of ASTX029, a dual-mechanism inhibitor of ERK1/2, in relapsed/refractory solid tumors. Journal Of Clinical Oncology 2022, 40: 9085-9085. DOI: 10.1200/jco.2022.40.16_suppl.9085.Peer-Reviewed Original ResearchRefractory solid tumorsPhase 1 studyCentral serous retinopathyDose levelsSolid tumorsPartial responseOpen-label phase 1 studyPhase 1bNon-small cell lung cancerTarget exposurePD effectsDose-limiting toxicity eventsPhase 2 dosePhase 2 studyPreliminary clinical activityCell lung cancerDaily dose levelsDose-escalation designDays of dosingFresh tumor biopsiesClass of drugsPhase 1aExtracellular signal-regulated kinase 1/2 (ERK1/2) inhibitorNSCLC subjectsOcular AEs
2021
484 Preliminary efficacy of the IL-15 superagonist SO-C101 in combination with pembrolizumab in patients with advanced/metastatic solid tumors
Garralda E, Galvao V, Champiat S, LoRusso P, Grell P, Naing A, Janku F, Sachse R, Bechard D, Kiemle-Kallee J, Marabelle A, Garralda E. 484 Preliminary efficacy of the IL-15 superagonist SO-C101 in combination with pembrolizumab in patients with advanced/metastatic solid tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a514-a514. DOI: 10.1136/jitc-2021-sitc2021.484.Peer-Reviewed Original ResearchStudy drug-related adverse eventsDrug-related adverse eventsCytokine release syndromeDose-limiting toxicityAdverse eventsCommon study drug-related adverse eventsAnti-programmed cell death protein 1 antibodyGrade 3 cytokine release syndromeSolid tumorsCell death protein 1 antibodyAnti-PD-1 therapyLong-term stable diseaseLocal injection site reactionsSkin squamous cell carcinomaPhase 2 dosePrevious systemic therapyTreatment-related deathsInjection site reactionsMetastatic solid tumorsAdditional clinical benefitDose-escalation designProtective memory responsesProtein 1 antibodySquamous cell carcinomaAvailable safety data502 Recommended phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the IL-15 superagonist SO-C101 as monotherapy in patients with advanced/metastatic solid tumors
Marabelle A, Champiat S, Galvao V, Naing A, Janku F, LoRusso P, Grell P, Sachse R, Bechard D, Kiemle-Kallee J, Garralda E. 502 Recommended phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the IL-15 superagonist SO-C101 as monotherapy in patients with advanced/metastatic solid tumors. 2021, a534-a534. DOI: 10.1136/jitc-2021-sitc2021.502.Peer-Reviewed Original ResearchPhase 2 doseDose-limiting toxicityAdverse eventsPartial responseStable diseaseTransaminase increaseSolid tumorsDrug-related adverse eventsIL-15 receptor αCutaneous squamous cell carcinomaLocal injection site reactionsPrevious systemic therapyResults Thirty patientsSignificant partial responseTreatment-related deathsCommon adverse eventsFlu-like syndromeRelated adverse eventsInjection site reactionsMetastatic solid tumorsAdditional clinical benefitDose-escalation designSquamous cell carcinomaDose-dependent increaseT cell activationA phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors.
Puzanov I, LoRusso P, Papadopoulos K, Chen C, LeBruchec Y, He X, Cousin T, Havenith K, Boni J, Bendell J. A phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2021, 39: 2556-2556. DOI: 10.1200/jco.2021.39.15_suppl.2556.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAdvanced solid tumorsDisease control rateSolid tumorsDose escalationGrade treatment-emergent adverse eventsNon-small cell lung cancerTumor-specific immune responsesTriple-negative breast cancerDose-escalation partPhase 2 dosePrior systemic therapyAntitumor activityMedian treatment durationOpen-label studyDose-escalation studyPhase 1b trialPrimary tumor typeRegulatory T cellsCell lung cancerPreliminary antitumor activityPK/PD dataRenal cell carcinomaSolid tumor modelsAntibody-drug conjugatesA first-in-human study of mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose escalation results.
Tolcher A, Carneiro B, Dowlati A, Razak A, Chae Y, Villella J, Coppola S, Englert S, Phillips A, Souers A, Salman Z, Penugonda S, Powderly J, LoRusso P. A first-in-human study of mirzotamab clezutoclax as monotherapy and in combination with taxane therapy in relapsed/refractory solid tumors: Dose escalation results. Journal Of Clinical Oncology 2021, 39: 3015-3015. DOI: 10.1200/jco.2021.39.15_suppl.3015.Peer-Reviewed Original ResearchRefractory solid tumorsAdverse eventsCell lung cancerSolid tumorsLymphocyte countLung cancerNon-small cell lung cancerSmall cell lung cancerMedian age 62 yearsCommon adverse eventsDose-expansion phasePhase 2 dosePrior systemic therapyTolerable safety profileFatal adverse eventsFatal cardiac arrestOverall response rateAge 62 yearsDose-escalation resultsAnti-tumor activityECOG 0ECOG 1RECIST v1.1Taxane therapyMedian durationPhase 1 trial of a novel, first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in patients with advanced or recurrent treatment-refractory solid malignancies.
Muller C, Brown-Glaberman U, Chaney M, Garyantes T, LoRusso P, McQuade J, Mita A, Mita M, Natale C, Orloff M, Papadopoulos K, Sato T, Yilmaz E, Rodon J. Phase 1 trial of a novel, first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in patients with advanced or recurrent treatment-refractory solid malignancies. Journal Of Clinical Oncology 2021, 39: 3084-3084. DOI: 10.1200/jco.2021.39.15_suppl.3084.Peer-Reviewed Original ResearchG protein-coupled estrogen receptorC-Myc depletionStable diseaseDose levelsMetastatic solid tumor malignanciesAnti-PD-1 antibodyProtein-coupled estrogen receptorHr of dosingPhase 2 doseRECIST partial responseTreatment-related SAEsImmune checkpoint inhibitorsPhase 1 trialSolid tumor malignanciesPK/PD dataSelective small molecule agonistHigh unmet needDays of treatmentAnti-tumor activityEstrogen receptor agonistsSmall molecule agonistsTumor immune recognitionG protein-coupled receptorsAnti-cancer therapyCombination cohortSafety and preliminary efficacy from the phase 1 portion of MasterKey-01: A First-in-human dose-escalation study to determine the recommended phase 2 dose (RP2D), pharmacokinetics (PK) and preliminary antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients (pts) with advanced solid malignancies.
Schram A, Ahnert J, Patel M, Jauhari S, Sachdev J, Zhu V, LoRusso P, Nguyen D, Le X, O'Connor M, Waters N, Cook C, Witt K, Humphrey R, Janne P, Hamilton E. Safety and preliminary efficacy from the phase 1 portion of MasterKey-01: A First-in-human dose-escalation study to determine the recommended phase 2 dose (RP2D), pharmacokinetics (PK) and preliminary antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients (pts) with advanced solid malignancies. Journal Of Clinical Oncology 2021, 39: 3086-3086. DOI: 10.1200/jco.2021.39.15_suppl.3086.Peer-Reviewed Original ResearchFE cohortHER2 amplificationSolid tumorsHuman dose-escalation studyDose-escalation cohortsManageable safety profilePhase 2 doseAdvanced solid malignanciesAdvanced solid tumorsDose-escalation studyMetastatic solid tumorsPreliminary antitumor activityPhase 1 portionAnti-tumor activityTumor growth inhibitionBID cohortQD scheduleEGFR/HER2Adverse eventsEscalation cohortsPartial responseProgressive diseaseStandard therapySafety profilePreliminary efficacyClinical pharmacokinetics of bdtx-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study.
Waters N, Patel M, Schram A, Ahnert J, Jauhari S, Sachdev J, Zhu V, LoRusso P, Nguyen D, Hong D, Tarilonte L, Humphrey R, Janne P, Hamilton E, Witt K. Clinical pharmacokinetics of bdtx-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study. Journal Of Clinical Oncology 2021, 39: 3097-3097. DOI: 10.1200/jco.2021.39.15_suppl.3097.Peer-Reviewed Original ResearchHigh-fat mealFasted stateEGFR WTRapid absorptionPK/PD profilesDose-escalation cohortsNon-fasting statePhase 2 doseAdvanced solid malignanciesHigh-fat breakfastSubset of patientsElimination t 1/2Serial blood samplesNon-compartmental methodsDose-dependent increaseSustained pharmacodynamic effectsMedian tmaxEscalation cohortsCrossover fashionDose escalationFat mealPharmacodynamic effectsSystemic exposureMultiple dosesClinical PharmacokineticsA phase 1 dose-escalation study of intravenously (IV) administered TAK-676, a novel STING agonist, alone and in combination with pembrolizumab in patients (pts) with advanced or metastatic solid tumors.
Falchook G, Luke J, Strauss J, Gao X, LoRusso P, VOON P, Li C, Shaw M, Gregory R, Horn K, Gibbs J, Lineberry N, Stumpo K, Malek K, Olszanski A. A phase 1 dose-escalation study of intravenously (IV) administered TAK-676, a novel STING agonist, alone and in combination with pembrolizumab in patients (pts) with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2021, 39: tps2670-tps2670. DOI: 10.1200/jco.2021.39.15_suppl.tps2670.Peer-Reviewed Original ResearchMetastatic solid tumorsCombination armCheckpoint inhibitorsSTING agonistsNovel STING agonistSolid tumorsDose escalationEastern Cooperative Oncology Group performance status 0Anti-programmed death ligand 1 therapyDay 1Phase 1 dose-escalation studyAnti-programmed death-1Death ligand 1 therapyPerformance status 0Phase 2 doseProinflammatory tumor environmentSolid Tumors (RECIST) v.Immune checkpoint inhibitorsDose-escalation studyResponse Evaluation CriteriaInnate immune cellsPreliminary antitumor activityStandard therapeutic optionAntitumor immune mechanismsImmuno-oncology therapiesA phase I/II study of combination olaparib and radium-223 in men with metastatic castration-resistant prostate cancer with bone metastases (COMRADE): A trial in progress.
Shaya J, Xie W, Saraiya B, Parikh M, Folefac E, Olson A, Choudhury A, Einstein D, Heath E, Parikh R, Kunos C, Ivy S, LoRusso P, Kurzrock R, Shapiro G, McKay R. A phase I/II study of combination olaparib and radium-223 in men with metastatic castration-resistant prostate cancer with bone metastases (COMRADE): A trial in progress. Journal Of Clinical Oncology 2021, 39: tps182-tps182. DOI: 10.1200/jco.2021.39.6_suppl.tps182.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPhase 2 componentCastration-resistant prostate cancerPhase 1 componentBone metastasesRadium-223PARP inhibitorsPrimary endpointOverall survivalProstate cancerPhase I/II studyRadiographic progression-free survivalFirst skeletal eventKey exclusion criteriaMore bone metastasesNon-bone metastasisPhase 2 doseStratification of responsePhase 1/2 studyPrior radiation therapyPhase 1/2 trialProgression-free survivalDose-escalation designTumor immune microenvironmentPlasma cell-free DNA