2024
Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors
Choi Y, Dharia N, Jun T, Chang J, Royer-Joo S, Yau K, Assaf Z, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman J, Shi Z, group A. Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors. Clinical Cancer Research 2024, 30: of1-of10. PMID: 38995268, PMCID: PMC11369623, DOI: 10.1158/1078-0432.ccr-24-0255.Peer-Reviewed Original ResearchConceptsKRAS G12C mutationTumor fractionSolid tumorsTumor typesG12C mutationOn-treatment time pointsNon-small cell lung cancerMutational heterogeneityAssociated with tumor typeProgression-free survivalPlasma samplesPhase 1 studyCell lung cancerCycle 1 dayAssociated with patient outcomesVariant allele frequencyAssociated with responseCtDNA levelsCtDNA profilingMetastatic sitesTruncal mutationsTumor DNATreatment responseLung cancerTumor tissuesA 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 failureA phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer.
Mukohara T, Park Y, Sommerhalder D, Yonemori K, Kim S, Kim J, Iwata H, Yamashita T, Layman R, Kim G, Im S, Lindeman G, Rugo H, Liyanage M, Homji Mishra N, Maity A, Bogg O, Liu L, Li M, LoRusso P. A phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer. Journal Of Clinical Oncology 2024, 42: 3006-3006. DOI: 10.1200/jco.2024.42.16_suppl.3006.Peer-Reviewed Original ResearchHER2- metastatic breast cancerTreatment-related adverse eventsMetastatic breast cancerCirculating tumor DNABreast cancerGene mutationsFrequent treatment-related adverse eventsMedian duration of follow-upAntitumor activityDuration of follow-upClinical benefit rateProgression-free survivalHER2 breast cancerMutant allele frequencyExpansion doseFulvestrant combinationMedian DoRESR1 mutationsMetastatic settingDose modificationEndocrine therapySystemic therapyMedian durationTumor DNACDK4/6 inhibitorsCirculating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors
Hu Y, Narayan A, Xu Y, Wolfe J, Vu D, Trinh T, Kantak C, Ivy S, Eder J, Deng Y, LoRusso P, Kim J, Patel A. Circulating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors. JCO Precision Oncology 2024, 8: e2300289. PMID: 38412387, PMCID: PMC10914240, DOI: 10.1200/po.23.00289.Peer-Reviewed Original ResearchConceptsCell-free circulating tumor DNANon-small-cell lung cancerSmall-cell lung cancerTriple-negative breast cancerPancreatic ductal adenocarcinomaAdvanced solid tumorsVariant allele fractionRadiographic responseOverall survivalCombination therapySolid tumorsCtDNA levelsLung cancerPretreated advanced solid tumorsDays of combination therapyMetastatic pancreatic ductal adenocarcinomaResponse to anticancer therapyAssociated with disease progressionProgression-free survivalPlasma samplesLead-inPoly(ADP-riboseInferior OSTumor DNASurvival outcomesEntinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial
Roussos Torres E, Ho W, Danilova L, Tandurella J, Leatherman J, Rafie C, Wang C, Brufsky A, LoRusso P, Chung V, Yuan Y, Downs M, O’Connor A, Shin S, Hernandez A, Engle E, Piekarz R, Streicher H, Talebi Z, Rudek M, Zhu Q, Anders R, Cimino-Mathews A, Fertig E, Jaffee E, Stearns V, Connolly R. Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial. Nature Cancer 2024, 5: 866-879. PMID: 38355777, DOI: 10.1038/s43018-024-00729-w.Peer-Reviewed Original ResearchHormone receptor-positive breast cancerReceptor-positive breast cancerTriple-negative breast cancerClinical benefit rateProgression-free survivalBreast cancerBenefit rateAdvanced HER2-negative breast cancerAdvanced triple-negative breast cancerHER2-negative breast cancerResponse rateNivolumab + ipilimumabPD-L1 statusDose-limiting toxicityPhase Ib trialTumor mutational burdenPhase II trialDose escalationExpansion cohortPD-L1II trialMutational burdenPrimary endpointSecondary endpointsMyeloid cells
2023
Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial
Desai J, Alonso G, Kim S, Cervantes A, Karasic T, Medina L, Shacham-Shmueli E, Cosman R, Falcon A, Gort E, Guren T, Massarelli E, Miller W, Paz-Ares L, Prenen H, Amatu A, Cremolini C, Kim T, Moreno V, Ou S, Passardi A, Sacher A, Santoro A, Stec R, Ulahannan S, Arbour K, Lorusso P, Luo J, Patel M, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Jun T, Dharia N, Schutzman J, Han S. Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial. Nature Medicine 2023, 30: 271-278. PMID: 38052910, PMCID: PMC10803265, DOI: 10.1038/s41591-023-02696-8.Peer-Reviewed Original ResearchPhase 1b trialColorectal cancerSafety profileMedian progression-free survivalTreatment-related adverse eventsInhibitor-naive patientsKRAS G12C inhibitionAntitumor activityManageable safety profileObjective response rateProgression-free survivalPreliminary antitumor activityKRAS G12C mutationKRAS G12C inhibitorsEpidermal growth factor receptorVariant allele frequencyGrowth factor receptorAdverse eventsMedian durationTreatment withdrawalPoor prognosisDisease progressionArm CDose reductionG12C inhibitorsSingle-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Sacher A, LoRusso P, Patel M, Miller W, Garralda E, Forster M, Santoro A, Falcon A, Kim T, Paz-Ares L, Bowyer S, de Miguel M, Han S, Krebs M, Lee J, Cheng M, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin M, Royer-Joo S, Chang J, Dharia N, Schutzman J, Desai J. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. New England Journal Of Medicine 2023, 389: 710-721. PMID: 37611121, DOI: 10.1056/nejmoa2303810.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalTreatment-related adverse eventsProgression-free survivalAdverse eventsSolid tumorsG12C mutationLow-grade adverse eventsGrade 3 eventsGrade 4 eventsTreatment-related deathsDiscontinuation of treatmentMetastatic solid tumorsPhase 1 studyDurable clinical responsesBiomarkers of responseKRAS G12C mutationAssessment of safetyVariant allele frequencyClinical responseColorectal cancerSerial assessmentDose reductionG12C inhibitorsPatientsTumor DNANCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors
Cecchini M, Walther Z, Wei W, Hafez N, Pilat M, Boerner S, Durecki D, Eder J, Schalper K, Chen A, LoRusso P. NCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors. Cancer Research Communications 2023, 3: 1113-1117. PMID: 37377610, PMCID: PMC10292219, DOI: 10.1158/2767-9764.crc-22-0485.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityHomologous recombination deficiencyPARP inhibitorsStable diseaseWeekly irinotecanObjective responseDay 1Day 3Solid tumorsPhase I dose-escalation studyTwice daily days 1I dose-escalation studyPhase I clinical trialDaily days 1Dose level 1Doses of veliparibGrade 3 neutropeniaMultiple-dose schedulesProgression-free survivalAdvanced solid tumorsDose-escalation studyEvaluable patientsNonoverlapping toxicitiesDose scheduleSystemic treatmentFirst-in-human first-in-class phase 1/2a study of the next generation CDK4-selective inhibitor PF-07220060 in patients (pts) with advanced solid tumors, enriched for HR+ HER2- mBC who progressed on prior CDK4/6 inhibitors and endocrine therapy.
Yap T, Giordano A, Hamilton E, LoRusso P, Bowers M, Basu C, Billotte S, Delioukina M, Liu F, Yang J, Sharma M. First-in-human first-in-class phase 1/2a study of the next generation CDK4-selective inhibitor PF-07220060 in patients (pts) with advanced solid tumors, enriched for HR+ HER2- mBC who progressed on prior CDK4/6 inhibitors and endocrine therapy. Journal Of Clinical Oncology 2023, 41: 3009-3009. DOI: 10.1200/jco.2023.41.16_suppl.3009.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsHR+/HER2- MBCEndocrine therapySolid tumorsCDK4/6 inhibitorsMedian progression-free survivalClinical benefit responseMedian prior linesDose-limiting toxicityProgression-free survivalAdvanced/metastatic breast cancerPhase 1/2a studyLines of treatmentFirst-in-humanDose-dependent increaseAnti-tumor activityDose expansionHER2-MBCSecondary/exploratory objectivesDose escalationData cutoffECOG PSSystemic therapyMedian ageMulticenter trialA phase Ia/Ib, dose-escalation/expansion study of the MDM2–p53 antagonist BI 907828 in patients (pts) with solid tumors: Safety and efficacy in patients with dedifferentiated liposarcoma (DDLPS).
LoRusso P, Gounder M, Yamamoto N, Patel M, Bauer T, Geng J, Sailer R, Tang Y, Jayadeva G, Schöffski P. A phase Ia/Ib, dose-escalation/expansion study of the MDM2–p53 antagonist BI 907828 in patients (pts) with solid tumors: Safety and efficacy in patients with dedifferentiated liposarcoma (DDLPS). Journal Of Clinical Oncology 2023, 41: 11554-11554. DOI: 10.1200/jco.2023.41.16_suppl.11554.Peer-Reviewed Original ResearchTreatment-related AEsProgression-free survivalManageable safety profileOverall response rateDedifferentiated liposarcomaSafety profileCohort 1Day 1Phase IbSolid tumorsMedian progression-free survivalDisease control rateECOG PS 0/1MDM2-p53 antagonistsPrior systemic therapySmall intestine obstructionSubgroups of ptsAdvanced solid tumorsFirst-line treatmentPreclinical antitumor activityFast track designationIA/IBPS 0/1Serious AEsPrimary endpointMulticenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma
Fanucci K, Pilat M, Shyr D, Shyr Y, Boerner S, Li J, Durecki D, Drappatz J, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma. Cancer Research Communications 2023, 3: 192-201. PMID: 36968138, PMCID: PMC10035510, DOI: 10.1158/2767-9764.crc-22-0436.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalProlonged stable diseaseStable diseasePhase II trialGrade 4 tumorsII trialOlaparib monotherapyGrade 2Multicenter phase 2 trialSingle-arm phase II trialWorld Health Organization classificationMedian overall survivalNeuro-Oncology criteriaPhase 2 trialOverall response rateFuture patient stratificationMutant gliomasPARP inhibitor olaparibEvaluable patientsPrimary endpointOverall survivalProgressive diseaseSelect patientsClinical benefitA First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas
Gounder M, Bauer T, Schwartz G, Weise A, LoRusso P, Kumar P, Tao B, Hong Y, Patel P, Lu Y, Lesegretain A, Tirunagaru V, Xu F, Doebele R, Hong D. A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas. Journal Of Clinical Oncology 2023, 41: 1714-1724. PMID: 36669146, PMCID: PMC10022862, DOI: 10.1200/jco.22.01285.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalDisease control rateProgression-free survivalControl rateDedifferentiated liposarcomaGrade 3/4 drug-related adverse eventsMurine double minute 2 inhibitorsSolid tumorsIntermittent scheduleDrug-related adverse eventsHuman Phase I StudyRandomized phase III trialPhase II doseAdvanced solid tumorsPhase III trialsIntermittent dosing scheduleSingle-agent activityPhase I studiesHuman phase IAdvanced liposarcomaAdverse eventsIII trialsDosing schedulesAdvanced cancerEfficacy analysis
2022
Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma.
Fanucci K, Pilat M, Shah R, Boerner S, Li J, Durecki D, Drappatz J, Collichio F, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Bao X, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma. Journal Of Clinical Oncology 2022, 40: 2035-2035. DOI: 10.1200/jco.2022.40.16_suppl.2035.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalStable diseaseDuration of responseOverall response ratePARP inhibitorsOverall survivalStandard therapyOlaparib monotherapyMulticenter phase 2 trialCDKN2A deletionClinical predictive markersGrade 3 lymphopeniaProlonged stable diseasePhase 2 trialGrade 4 tumorsFuture patient stratificationRecent preclinical studiesHigh-grade gliomasNovel drug combinationsContrast-enhancing gliomasEligible ptsEvaluable ptsRecent histologyPrimary endpointPhase 1 study of SGN-ALPV, a novel, investigational vedotin antibody–drug conjugate directed to ALPP/ALPPL2 in advanced solid tumors (SGNALPV-001, trial in progress).
Lakhani N, Friedman C, Perez C, Wehr A, McGoldrick S, LoRusso P. Phase 1 study of SGN-ALPV, a novel, investigational vedotin antibody–drug conjugate directed to ALPP/ALPPL2 in advanced solid tumors (SGNALPV-001, trial in progress). Journal Of Clinical Oncology 2022, 40: tps3159-tps3159. DOI: 10.1200/jco.2022.40.16_suppl.tps3159.Peer-Reviewed Original ResearchMonomethyl auristatin EAdvanced solid tumorsSolid tumorsNon-small cell lungTesticular germ cell tumorsECOG PS 0Objective response rateProgression-free survivalDose-limiting toxicityPhase 1 studyDuration of responseGerm cell tumorsDisease-specific cohortsPromising preclinical dataImmunogenic cell deathClinical trial informationNormal tissue expressionAntibody-drug conjugatesMechanism of actionProtease-cleavable linkerAdult ptsCumulative safetyRECIST v1.1Exploratory endpointsMeasurable disease
2021
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.
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
2020
A phase I study of CD40 agonist ABBV-927 plus OX40 agonist ABBV-368 with or without the PD-1 inhibitor budigalimab in patients with advanced solid tumors.
Powderly J, Tolcher A, LoRusso P, Blaney M, Dacosta D, Henner W, McDevitt M, Miller K, Golan T. A phase I study of CD40 agonist ABBV-927 plus OX40 agonist ABBV-368 with or without the PD-1 inhibitor budigalimab in patients with advanced solid tumors. Journal Of Clinical Oncology 2020, 38: tps3147-tps3147. DOI: 10.1200/jco.2020.38.15_suppl.tps3147.Peer-Reviewed Original ResearchNon-small cell lung cancerTriple-negative breast cancerAdvanced solid tumorsDisease-specific cohortsSolid tumorsCostimulatory moleculesEastern Cooperative Oncology Group performance statusCentral nervous system metastasesPD-ligand 1 (PD-L1) inhibitorsRegulatory T cell activityNascent immune responsesPhase 2 doseNervous system metastasesProgression-free survivalPhase 1 studyT cell activityCell lung cancerDuration of responseOverall response ratePlatinum-based therapyKey costimulatory moleculesT cell activationAdaptive immune systemPrimary endpointSecondary endpointsTrial 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
2019
First-in-Human Study of Mivebresib (ABBV-075), an Oral Pan-Inhibitor of Bromodomain and Extra Terminal Proteins, in Patients with Relapsed/Refractory Solid Tumors
Piha-Paul SA, Sachdev JC, Barve M, LoRusso P, Szmulewitz R, Patel SP, Lara PN, Chen X, Hu B, Freise KJ, Modi D, Sood A, Hutti JE, Wolff J, O'Neil BH. First-in-Human Study of Mivebresib (ABBV-075), an Oral Pan-Inhibitor of Bromodomain and Extra Terminal Proteins, in Patients with Relapsed/Refractory Solid Tumors. Clinical Cancer Research 2019, 25: 6309-6319. PMID: 31420359, DOI: 10.1158/1078-0432.ccr-19-0578.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsDose escalationSolid tumorsStable diseaseSafety profileProstate cancerCommon grade 3/4 treatment-emergent adverse eventsGrade 3/4 treatment-emergent adverse eventsHuman studiesMost common treatment-emergent adverse eventsCommon treatment-emergent adverse eventsMedian progression-free survivalTolerable safety profilePhase II doseAdvanced solid tumorsProgression-free survivalRefractory solid tumorsPreliminary antitumor activityMalignant solid tumorsAminotransferase elevationEvaluable patientsDose expansionExpansion cohortGastrointestinal bleedAdverse events
2013
A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC).
Goncalves P, Kummar S, Siu L, Hansen A, Savvides P, Sukari A, Chao J, Heilbrun L, Pilat M, Smith D, Casetta L, Boerner S, LoRusso P. A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC). Journal Of Clinical Oncology 2013, 31: 6045-6045. DOI: 10.1200/jco.2013.31.15_suppl.6045.Peer-Reviewed Original ResearchProgression-free survivalAdenoid cystic carcinomaSuberoylanilide hydroxamic acidMetastatic adenoid cystic carcinomaOverall survivalAdverse eventsResponse durationResponse rateEvaluable patientsOnly grade 3 adverse eventGrade 3 adverse eventsMedian progression-free survivalTreatment of ACCAdequate organ functionMedian overall survivalPhase II studyPhase II trialHistone deacetylasesDrug combination studiesChemo-naïveChemotherapy regimensII trialOral painSecondary endpointsThromboembolic eventsPhase II clinical activity and tolerability of the SMAC-mimetic birinapant (TL32711) plus irinotecan in irinotecan-relapsed/refractory metastatic colorectal cancer.
Senzer N, LoRusso P, Martin L, Schilder R, Amaravadi R, Papadopoulos K, Segota Z, Weng D, Graham M, Adjei A. Phase II clinical activity and tolerability of the SMAC-mimetic birinapant (TL32711) plus irinotecan in irinotecan-relapsed/refractory metastatic colorectal cancer. Journal Of Clinical Oncology 2013, 31: 3621-3621. DOI: 10.1200/jco.2013.31.15_suppl.3621.Peer-Reviewed Original ResearchMedian progression-free survivalProgression-free survivalClinical activityRefractory/BP riskOverall clinical benefit rateRefractory metastatic colorectal cancerKRAS-MTBest supportive careClinical benefit rateMetastatic colorectal cancerReversible side effectsPhase 1 studySMAC mimetic birinapantAnti-tumor synergyPrior regimensSupportive careClinical benefitColorectal cancerKRAS WTOngoing treatmentSmac mimeticsBenefit rateMedian numberTherapeutic synergy