DREAMM-6: Safety And Tolerability Of Belantamab Mafodotin .
Presentation number: 8502DREAMM-6: Safety and Tolerability ofBelantamab Mafodotin in Combination withBortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma (RRMM)Ajay Nooka MD1, Keith Stockerl-Goldstein MD2, Hang Quach, MD3 Adam Forbes4, Maria VictoriaMateos MD5, Amit Khot MD6, Alan Tan MD7, Rafat Abonour MD8, Bikramjit Chopra PhD9, Rachel Rogers MS10,Geraldine Ferron-Brady PhD10, Jacqueline Davidge PhD9, Steve Frey MS10, Anne Yeakey MD10, Mala Talekar MD10,Katarina Luptakova MD10, Ira Gupta MD10, Rakesh Popat MD111EmoryUniversity, Winship Cancer Institute, Atlanta, GA, USA; 2Washington University Medical School, St. Louis, MO, USA; 3University of Melbourne, St. Vincent’s Hospital Melbourne, Melbourne, VIC, Australia;Cornwall Hospital, Truro, UK; 5University Hospital of Salamanca-Instituto de Investigación Biomédica de Salamanca, Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain; 6Peter MacCallumCancer Centre and Royal Melbourne Hospital, VIC, Australia; 7Cancer Treatment Centers of America, University of Arizona College of Medicine, Phoenix, AZ, USA; 8Queen Elizabeth Hospital, Adelaide, SouthAustralia, Australia; 9GlaxoSmithKline, Uxbridge, Middlesex, UK; 10GlaxoSmithKline, Upper Providence, PA, USA; 11University College London Hospitals, NHS Foundation Trust, London, UK.4Royalhttp://tago.ca/ASCO 18Copies of this presentation obtained through Quick Response (QR) Code are for personal use only and may not be reproduced without permission from ASCO and the author of this presentationAjay Nooka
DisclosuresThis slide will be automatically created for youby ASCO and inserted in your presentationAjay Nooka2
Belamaf Is An Ideal Candidate For Use In Combination With Other TreatmentsBelantamab Mafodotin (belamaf; GSK2857916) is afirst-in-class anti-BCMA antibody-drug conjugate witha multimodal MoA1,2ADC1Outcomeat 13-month BCMAMalignantplasmacell3Markers of ICDIn the Phase II DREAMM-2 study, single-agent belamafdemonstrated deep and durable responses in patients withheavily pre-treated RRMM3,4*EffectorcellBelamaf2.5 mg/kg (n 97)Belamaf3.4 mg/kg (n 99)31 (32)(21.7–43.6)35 (35)(24.8–47.0)Median DoR,months (95% CI)11.0 (4.2–NR)6.2 (4.8–NR)Median PFS,months (95% CI)2.8 (1.6–3.6)3.9 (2.0–5.8)Median OS,months (95% CI)13.7 (9.9–NR)13.8 (10.0–NR)ORR†, n (%)(97.5% CI)In DREAMM-2, belamaf showed an acceptable safety profile3,4*Refractory to an immunomodulatory agent, a proteasome inhibitor, and refractory and/or intolerant to an anti-CD38 monoclonal antibody †Defined as partial response or better.ADC, antibody-drug conjugate; ADCC/P, antibody-dependent cellular cytotoxicity/phagocytosis; BCMA, B-cell maturation antigen; Belamaf, belantamab mafodotin; CI, confidence interval; DoR, duration of response; DREAMM, DRiving Excellence in Approaches toMultiple Myeloma; ICD, immunogenic cell death; MoA, mode of action; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression free survival; RRMM, relapsed or refractory multiple myeloma1. Tai YT et al. Blood. 2014;123:3128–38; 2. Tai YT & Anderson KC. Immunotherapy 2015; 7:1187–99; 3. Lonial S et al. Lancet Oncol 2020;21:207–21; 4. Lonial S et al. ASCO 2020 poster 436.Ajay Nooka3
DREAMM-6 Study DesignAn ongoing, two-part, two-arm, open-label, Phase I/II study of Belamaf in combination with LenDex and BorDexin patients with RRMM previously treated with 1 prior therapy (NCT03544281)*Arm A: Belamaf with LenDex (B-Rd)Part 2:Dose ExpansionPart 1: Dose EscalationB-Rd3.4 mg/kgSINGLEa,en 3DEB-Rd3.4 mg/kgSPLITb,dn 3DEB-Rd2.5 mg/kgSINGLEa,bn 3DE/AmendmentDEB-Rd2.5 mg/kgSINGLEa,b SPLITb,cn 3n 3Arm B: Belamaf with BorDex (B-Vd)Part 1: Dose EscalationExpansionn 9DESINGLEn 9SPLITn 9B-Vd2.5 mg/kg SINGLE †n 12B-Vd2.5 mg/kg SPLIT §n 12Expansionn 9ExpansionB-Vd3.4 mg/kg SINGLE †n 6Part 2: Dose ExpansionB-Vd‡2.5 mg/kg SINGLE†n 6B-Rd1.9 mg/kgSINGLEa,bn 3B-Vd3.4 mg/kg SINGLE †n 9B-Vd3.4 mg/kg SPLIT¶n 12*Combination therapy continued for up to 8 cycles. Thereafter, belamaf monotherapy further continued until disease progression, death, intolerable toxicity, consent withdrawn. Cohorts followed-up for PFS and OSa. Belamaf SINGLE full assigned dose of belamaf administered on Day 1 of any 28-day cycle b. Lenalidomide (25 mg on Days 1-21) dexamethasone (40 mg on Days 1, 8, 15, and 22) of any 28-day cycle; c. belamaf 2.5 mg/kg SPLIT 1.25 mg/kg on Day 1 and 1.25mg/kg on Day 8 of any 28-day cycle; d. belamaf 3.4 mg/kg SPLIT 1.7 mg/kg on Day 1 and 1.7 mg/kg on Day 8 of any 28-day cycle; e. belamaf 3.4 mg/kg SINGLE May be evaluated based on risk/benefit assessment of GSK2857916 3.4 mg/kg SPLIT;†Belamaf SINGLE full assigned dose of belamaf administered on Day 1 of any 21-day cycle ‡Bortezomib (1.3 mg/m2 on Days 1, 4, 8, and 11) dexamethasone (20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12) of any 21-day cycle. §Belamaf 2.5 mg/kg SPLIT 1.25 mg/kg on Day 1 and 1.25mg/kg on Day 8 of any 21-day cycle. ¶Belantamab mafodotin 3.4 mg/kg SPLIT 1.7 mg/kg on Day 1 and 1.7 mg/kg on Day 8 of any 21-day cycle.Belamaf, belantamab mafodotin; BorDex, bortezomib/dexamethasone; B-Rd, Belamaf/lenalidomide/dexamethasone; B-Vd, belamaf/bortezomib/dexamethasone; DE, dose escalation; DREAMM, Driving Excellence in Approaches to Multiple Myeloma; LenDex,lenalidomide/dexamethasone; RRMM, relapsed or refractory multiple myeloma.Ajay Nooka4
DREAMM-6 Arm B Study DesignBelamaf 2.5mg/kg SINGLE dosing in combination with BorDex in patients with RRMM previously treated with 1 prior therapy(NCT03544281)*Part 1: Dose EscalationB-Vd3.4 mg/kg SINGLEn 6B-Vd‡2.5 mg/kg SINGLE†n 6No DLTs observedfor either2.5 mg/kg or3.4 mg/kg cohortsin Part 1Part 2: Dose Expansion1Primary Objective2Secondary ObjectivesB-Vd2.5 mg/kg SINGLEn 12Preliminary clinical activityof B-VdB-Vd2.5 mg/kg SPLIT §n 12Further safety/tolerabilityevaluation of B-VdB-Vd3.4 mg/kg SINGLEn 9PK evaluations of B-Vd,including ADASafety, tolerabilityand ORR of B-VdcombinationB-Vd3.4 mg/kg SPLIT¶n 12HRQoL impact of B-Vd*Combination therapy continued for up to 8 cycles. Thereafter, belamaf monotherapy further continued until disease progression, death, intolerable toxicity, consent withdrawn. Cohorts followed-up for PFS and OS.†Belamaf SINGLE full assigned dose of belamaf administered on Day 1 of any 21-day cycle. ‡Bortezomib (1.3 mg/m2 on Days 1, 4, 8, and 11) dexamethasone (20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12) of any 21-day cycle. §Belamaf 2.5 mg/kg SPLIT 1.25 mg/kg onDay 1 and 1.25 mg/kg on Day 8 of any 21-day cycle. ¶Belantamab mafodotin 3.4 mg/kg SPLIT 1.7 mg/kg on Day 1 and 1.7 mg/kg on Day 8 of any 21-day cycle; ADA, Anti-Drug-Antibodies; BCMA, B-cell maturation antigen; BorDex, bortezomib/dexamethasone; B-Vd,belamaf/bortezomib/dexamethasone; DREAMM, Driving Excellence in Approaches to Multiple Myeloma; HRQoL, health related quality of life; PK, pharmacokinetics; RRMM, relapsed or refractory multiple myeloma.Ajay Nooka5
DREAMM-6 Arm B Dosing ScheduleBelamaf 2.5mg/kg SINGLE dosing in combination with BorDex in patients with RRMM previously treated with 1 prior therapy(NCT03544281)*Key Eligibility Criteria:B-Vd Dosing Schedule‡ 1 prior therapyPatients refractory tobortezomib were not excludedMeasurable disease†ECOG 0–2Adequate organsystem functionArm B2.5 mg/kg SINGLEQ3W dosing21-day cycleNot exposed to a mAb therapywithin 30 daysBelamaf 2.5 mg/kg SINGLE doseon D1 of every 3-week cycle181521BelamafPrior autologous-stemcell transplant allowedor transplant-ineligibleBortezomib(Cycles 1-8)Dexamethasone(Cycles 1-8)*Combination therapy continued for up to 8 cycles. Thereafter, belamaf monotherapy further continued until disease progression, death, intolerable toxicity, consent withdrawn. Cohorts followed-up for PFS and OS; †Measurable disease defined as serum myelomaprotein (M-protein) 0.5 g/dL and/or urine M-protein 200 mg/24h and/or serum free-light chain (FLC) assay: Involved FLC level 10 mg/dL and an abnormal serum FLC ratio ( 0.26 or 1.65); ‡Dose delays or reductions can be used to manage adverse events. Belamaf,belantamab mafodotin; BorDex, bortezomib/dexamethasone; B-Vd, belamaf/bortezomib/dexamethasone; DREAMM, Driving Excellence in Approaches to Multiple Myeloma; ECOG, Easter Cooperative Oncology Group performance status; mAb, monoclonal antibody;RRMM, relapsed or refractory multiple myeloma.Ajay Nooka6
DREAMM-6 Arm B: Patient Demographics and Baseline Disease CharacteristicsCharacteristicB-Vd‡ (n 18)Age, years; median (range)Sex, n (%)MaleFemaleRace, African-American, n (%)Number of prior lines of therapy, n (%)12–34–6 7Median number of prior lines of therapy (range)ISS Stage, n (%)IIIIIIUnknownECOG, n (%)0–1 2High-risk cytogenetics, n (%)*67 (47–83)11 (61)7 (39)4 (22)4 (22)6 (33)4 (22)4 (22)3 (1–11)4833(22)(44)(17)(17)15 (83)3 (17)6† (33)*Defined as t(4;14), t(14;16), or del17p13; †Cytogenetic data were not available for 6 patients; ‡Belamaf 2.5 mg/kg SINGLE BorDexB-Vd, belantamab mafodotin/bortezomib/dexamethasone; ECOG, Easter Cooperative Oncology Group performance status; ISS, International Staging System; PI, proteasome inhibitor.Ajay Nooka7
DREAMM-6 Arm B: Time on TreatmentAs of data-cut-off date of March 30 2020, belamaf 2.5 mg/kg SINGLE BorDex patients had a median of18.2 (range, 6.0–46.4) weeks on treatmentDREAMM-6 Arm B: Overview of Adverse EventsPatients with AE, n (%)B-Vd¶ (n 18) [Part 1 Part 2]AE related to study treatmentGrade 3/4 AEAEs leading to permanent discontinuation of a study treatmentAEs leading to permanent discontinuation of belamafAE leading to dose reductionsKeratopathy (MECs) leading to dose reductionThrombocytopenia AE leading to dose reductionAE leading to dose interruption/delayKeratopathy (MECs) leading to dose interruption/delayThrombocytopenia AE leading to dose interruption/delayAny SAEFatal SAESAE related to study treatment18 (100)16 (89)5 (28)†0‡13 (72)7 (39)6 (33)18* (100)15 (83)7 (39)12 (67)0**5 (28)¶Belamaf 2.5 mg/kg SINGLE BorDex; †4/5 discontinued bortezomib, 2/5 discontinued dexamethasone; 4/5 remain on the study receiving belamaf monotherapy; ‡8/13 had an AE leading to a dose reduction in belamaf; Changes to the corneal epithelium observed oneye examination (corneal events/keratopathy/microcyst-like epithelial changes [MECs]); *16/18 had an AE leading to a dose interruption/delay in belamaf; **3/5 SAEs were related to belamaf treatment, 4/5 were related to bortezomib, 2/4 were related todexamethasone and 1/5 was an undefined causality; AE, Adverse event; B-Vd, belantamab mafodotin/bortezomib/dexamethasone; DLT, dose limiting toxicity; SAE, serious adverse event.Ajay Nooka8
DREAMM-6 Arm B: AESI by Maximum GradeBelamaf 2.5 mg/kg SINGLE BorDex (n 18) [Part 1 Part 2] preliminary AESI dataPatients with an event(% of all patients)100IRRThere were no Grade 5 events90Thrombocytopenia80Keratopathy (MECs)There were no Grade 4corneal events7060Dose delays or reductions could be used tomanage AEn 1050B-Vd had a manageable safety profileconsistent with that of the individualcomponentsn 8n 74030n 320100GRADEn 11Data are not sufficiently mature to reportresolution of corneal events at this timen 3n 123*4†Maximum CTCAE v4.03 Grade5[In DREAMM-2, at limited follow-up, visionhad returned to baseline/near baseline in69/85 (81%) affected patients. Nopermanent loss of vision was reported]11. Lonial S et al. Lancet Oncol 2020;21:207–21*Grade 3: Severe or medically significant but not immediately sight-threatening, hospitalization or prolongation of existing hospitalization indicated, limiting self-care or activities of daily living; †Grade 4. Sight-threatening consequences; urgent intervention indicated;blindness(20/200 or worse) in the affected eye. AESI, adverse event of special interest; BorDex, bortezomib/dexamethasone; IRR, infusion related reaction; MECs, microcyst-like epithelial changes; Thrombocytopenia includes MeDRA preferred terms platelet countdecreased, thrombocytopenia; Keratopathy (corneal events/MECs) encompasses many preferred terms; most commonly reported symptoms related to corneal events include blurred vision, dry eye, photophobia, foreign body sensation and eye pain; most commonlyreported exam findings include keratopathy.Ajay Nooka9
DREAMM-6 Arm B: Investigator-Assessed Best Confirmed ResponseBelamaf 2.5 mg/kg SINGLE BorDex (n 18) [Part 1 Part 2] preliminary best confirmed response data1008070VGPR50%n 96050403020100PR28%n 5MR 6%,n 1SD17%n 3ORR 78%Patients with response (%)90In patients with 1 prior line of therapy,B-Vd treatment had an ORR of 78%(95% CI 52.4–93.6)CBR was 83% (95% CI 58.6–96.4)All patients had an evaluable responseIn patients with 1prior line oftherapy, Vdtreatmentdemonstrated anORR of 50% 63%1–350% of patients experienced VGPRDoR is not yet reached*Investigator-assessed best confirmed response (International Myeloma Working Group 2016 criteria). No patients had stringent complete response (sCR), complete response (CR), or progressive Disease.B-Vd, belamaf/bortezomib/dexamethasone; CBR, Clinical Benefit Rate (sCR CR VGPR PR MR), CI, confidence Interval based on exact method; MR, minimal response; ORR, overall response rate (sCR CR VGPR PR); PR, partial response; SD, stable disease; Vd,bortezomib/dexamethasone; VGPR, very good partial response.1. Palumbo A, et al. N Engl J Med 2016;375:754–66; 2. San-Miguel F, et al. Lancet Oncol. 2014;15(11):1195–206; 3. Richardson P, et al. Lancet Oncol. 2019;20(6):781–94.Ajay Nooka10
ConclusionsTo date, 59 patients have been treated with B-Vd (belamaf and BorDex in combination) in Arm Bof DREAMM-6 Of these, 18 have received 2.5mg/kg Q3W (SINGLE) dose of belamaf in combination with standard-dose BorDexPreliminary data indicate that the combination of 2.5 mg/kg Q3W belamaf with BorDex has anacceptable safety profile The main AEs were:– Keratopathy* (MECs; as expected for belamaf, managed with dose modifications)– Thrombocytopenia (as expected for both belamaf and Bor)Preliminary investigator-assessed best response data indicate an ORR of 78%, a VGPR of 50%,and CBR of 83% with belamaf 2.5 mg/kg BorDex in participants with RRMM with median 3 prior linesof therapy (range 1–11) DoR not yet reached and, response may be expected to deepen over timeThis study is currently ongoing. Data for the other dose-schedules in both arms are being collectedand will be presented at future meetings*Corneal events.Ajay Nooka11
Acknowledgements and Further InformationThe authors would like to thank the patients and study site staff, and our fellow study investigators:Bradley Augustson, Andrew Spencer, Peter Presgrave, Wilfrid Jaksic, Jaime Perez de Oteyza, Elham Askari,Merce Gironella Mesa, David Siegel, Noah Kornblum, Elizabeth Cull, Malin Hultcrantz, James Strauss, RyanRamaekers, Craig Cole and Ashish SangalStudy funded by GlaxoSmithKlineDrug linker technology licensed from Seattle GeneticsMonoclonal antibody produced using POTELLIGENT Technology licensed from BioWaMedical writing assistance provided by Martina Stagno D'Alcontres of Fishawack, funded by GlaxoSmithKlineBelamaf is being evaluated in other clinical trials in various MM settings and is being discussed at thismeeting: Posters 452 and 456 - Belamaf in combination with other agents Posters 436, 419 and 441 - Belamaf as monotherapyFor a plain language summary of this presentation please visit http://tago.ca/ASCO 23 or use the QR codeAjay Nooka12
Mateos MD5, Amit Khot MD6, Alan Tan MD7, Rafat Abonour MD8, Bikramjit Chopra PhD9, Rachel Rogers MS10, Geraldine Ferron-Brady PhD 10, Jacqueline Davidge PhD9, Steve Frey MS , Anne Yeakey MD10, Mala Talekar MD10, Katarina Luptakova MD
Efficacy was assessed using PANSS total scores at Days 4, 8, 22, 36, 64, and 92 (or study endpoint). Tolerability assessments included treatment-emergent adverse events reports and adverse-event related study discontinuations. Analysis Sets and Statistical Evaluations Onset of efficacy and tolerability analyses were per-
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