ClinicalTrials.gov Identifier: NCT

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1 Efficcy of Drtumumb, Lenlidomide, nd Dexmethsone Versus Lenlidomide nd Dexmethsone in Relpsed or Refrctory Multiple Myelom Ptients With to 3 Prior Lines of Therpy: Updted Anlysis of POLLUX Sd Z. Usmni, Meletios A. Dimopoulos, 2 Andrew Belch, 3 Drrell White, 4 Lotfi Benboubker, 5 Gordon Cook, Merv Leib, 7 Jmes Morton, 8 P. Joy Ho, 9 Kihyun Kim, Noki Tkezko, Nushmi Z. Khokhr, 2 Mry Guckert, 2 Kid Wu, 2 Xing Qin, 2 Tineke Csneuf, 3 Christopher Chiu, 2 A. Kte Ssser, 2 Jesus Sn-Miguel 4 Levine Cncer Institute/Crolins HelthCre System, Chrlotte, NC, USA; 2 Ntionl nd Kpodistrin University of Athens, Athens, Greece; 3 Deprtment of Oncology, University of Albert Cross Cncer Institute, Edmonton, Albert, Cnd; 4 QEII Helth Sciences Center, Dlhousie University, Hlifx, Nov Scoti, Cnd; 5 Service d Hémtologie et Thérpie Cellulire, Hôpitl Bretonneu, Centre Hospitlier Régionl Universitire (CHRU), Tours, Frnce; St Jmes's Institute of Oncology, Leeds Teching Hospitls NHS Trust nd University of Leeds, Leeds, UK; 7 Sheb Medicl Center, Tel Hshomer, Rmt Gn, Isrel; 8 Icon Cncer Cre, South Brisbne, QLD, Austrli; 9 Institute of Hemtology, Royl Prince Alfred Hospitl, Cmperdown, NSW, Austrli; Deprtment of Medicine, Smsung Medicl Center, Sungkyunkwn University School of Medicine, Seoul, South Kore; Deprtment of Hemtology, Ntionl Hospitl Orgniztion Disster Medicl Center of Jpn, Tchikw, Jpn; 2 Jnssen Reserch & Development, LLC, Spring House, PA, USA; 3 Jnssen Reserch & Development, Beerse, Belgium; 4 Clínic Universidd de Nvrr-CIMA, IDISNA, Pmplon, Spin. CliniclTrils.gov Identifier: NCT279

2 Bckground Drtumumb Humn monoclonl ntibody trgeting CD38 Direct on-tumor nd immunomodultory MoA -5 Approved As monotherpy for hevily pretreted RRMM by the FDA, EMA, Helth Cnd, Mexico, nd Singpore Combo with stndrd of cre regimens for RRMM fter prior therpy (POLLUX nd CASTOR) by the FDA Erly studies demonstrted efficcy of drtumumb Rpid, deep, nd durble responses Well tolerted with mngeble dverse events MoA, mechnism of ction; RRMM, relpsed or refrctory multiple myelom ; FDA, Food nd Drug Administrtion; EMA, Europen Medicines Agency; CDC, complement-medited cytotoxicity; ADCC, ntibody-dependent cell-medited cytotoxicity; ADCP, ntibody-dependent cellulr phgocytosis.. Lmmerts vn Bueren J, et l. Blood. 24;24. Abstrct Overdijk MB, et l. MAbs. 25;7(2): Overdijk MB, et l. J Immunol. 2;97(3): Krejcik J, et l. Blood. 2;28(3): de Weers M, et l. J Immunol. 2;8(3):

3 Study Design Multicenter, rndomized (:), open-lbel, ctive-controlled, phse 3 study Key eligibility criteri RRMM prior line of therpy Prior lenlidomide exposure, but not refrctory Cretinine clernce 3 ml/min Strtifiction fctors No. of prior lines of therpy ISS stge t study entry Prior lenlidomide R A N D O M I Z E : (n = 28) Drtumumb mg/kg IV Qw in Cycles to 2, q2w in Cycles 3 to, then q4w until PD R 25 mg PO Dys to 2 of ech cycle until PD d 4 mg PO 4 mg weekly until PD (n = 283) R 25 mg PO Dys to 2 of ech cycle until PD d 4 mg PO 4 mg weekly until PD Cycles: 28 dys Pre-mediction for the tretment group consisted of dexmethsone 2 mg, cetminophen, nd n ntihistmine Primry endpoint PFS Secondry endpoints TTP OS ORR, VGPR, CR MRD Time to response Durtion of response Sttisticl nlyses Primry nlysis: ~77 PFS events ISS, interntionl stging system;, drtumumb/lenlidomide/dexmethsone; IV, intrvenous; qw, weekly; q2w, every 2 weeks; q4w, every 4 weeks; PD, progressive disese; R, lenlidomide; PO, orl; d, dexmethsone;, lenlidomide/dexmethsone; PFS, progression-free survivl; TTP, time to progression; OS, overll survivl; ORR, overll response rte; VGPR, very good prtil response; CR, complete response; MRD, miniml residul disese. On drtumumb dosing dys, dexmethsone 2 mg ws dministered s pre-mediction on Dy nd Dy 2. 3

4 Chrcteristic Age, y Medin (rnge) 75, % ISS stge, % I II III Medin (rnge) time from dignosis, y Cretinine clernce (ml/min), % N >3- > Cytogenetic profile, (%) b N Stndrd risk High risk Bseline Demogrphic nd Clinicl Chrcteristics (n = 28) 5 (34-89) (.4-27.) (n = 283) 5 (42-87) (.4-2.7) Chrcteristic Prior lines of therpy, % Medin (rnge) 2 3 >3-3 c (n = 28) (-) (n = 283) (-8) Prior ASCT, % 3 4 Prior PI, % Prior bortezomib, % Prior IMiD, % Prior lenlidomide, % Prior PI + IMiD, % Refrctory to bortezomib, % 2 2 Refrctory to lst line of therpy, % ASCT, utologous stem cell trnsplnttion; PI, protesome inhibitor; IMiD, immunomodultory drug. ISS stging is derived bsed on the combintion of serum β2-microglobulin nd lbumin. b Centrl next-genertion sequencing. High-risk ptients hd ny of t(4;4), t(4;), or del7p. Stndrd-risk ptients hd n bsence of high-risk bnormlities. c Explortory. 4

5 % surviving without progression No. t risk HR, hzrd rtio; CI, confidence intervl; scr, stringent complete response; PR, prtil response. Note: PFS = ITT popultion; ORR = response-evluble popultion. Kpln-Meier estimte; b P <. for vs. Updted Efficcy HR:.37 (95% CI,.28-.5; P <.) Months month PFS % 49% Medin: not reched 5 5 Medin: 7.5 months ORR, % CR: 4% b Medin (rnge) follow-up: 7.3 (-24.5) months ORR = 93% P <. VGPR: 78% b ORR = 7% (n = 28) (n = 27) Responses continue to deepen in the group with longer follow-up CR: 2% VGPR: 45% scr CR VGPR PR 5

6 MRD-negtive Rte * * * 3.X 4.4X 4.8X * P <.. MRD-negtive rte, % Sensitivity threshold 4 5 MRD-negtive rtes were >3-fold higher t ll thresholds Intent-to-tret popultion. P vlues re clculted using likelihood-rtio chi-squre test.

7 PFS: MRD Sttus ( 5 ) 8 MRD negtive (n = ) MRD negtive (n = 7) % progression-free nd live 4 MRD positive (n = 25) MRD positive (n = 27) 2 No. t risk MRD negtive MRD negtive MRD positive MRD positive Months MRD negtivity is ssocited with better outcomes Intent to tret popultion. 7

8 Time From Lst Line of Therpy to Study Tretment of > or 2 Months >2 Months 8-month PFS 2 Months 8-month PFS 83% % surviving without progression % % surviving without progression Medin:.3 months 7% 37% HR:.37 (95% CI:.23-.; P <.) No. t risk Months >2 > HR:.38 (95% CI:.2-.55; P <.) Months is superior to regrdless of time since lst therpy Kpln-Meier estimte. b Response-evluble popultion. 8

9 Refrctory to Lst Line of Therpy 8-month PFS 9 ORR = 87% b P =. % surviving without progression No. t risk Medin:.3 months HR:.47 (95% CI:.29-.7; P =.5) 5% 3% Months ORR, % CR: 47% c (n = 78) CR: 5% VGPR: 73% c ORR = 4% b 9 3 (n = 73) scr CR VGPR PR VGPR: 34% benefits ptients refrctory to lst line of therpy Kpln-Meier estimte. b Response-evluble popultion. c P <. for vs. 9

10 PFS: Cytogenetic Risk in All Evluble Ptients Comprble results in to 3 prior lines popultion % surviving without progression No. t risk std risk std risk high risk high risk Months stndrd risk high risk stndrd risk high risk High risk Stndrd risk Medin PFS, mo HR (95% CI) P vlue ORR, % P vlue n = 28 n = 33 n = 3 NR 7..3 (.8-.49) <. n = 37 Medin PFS, mo NR.2 HR (95% CI) P vlue.44 (.9-.3).475 n = 27 n = 3 ORR, % 85 7 P vlue NS n = 32 n = improves outcomes regrdless of cytogenetic risk NR, not reched; NS, not significnt. ITT/Biomrker risk evluble nlysis set. High-risk ptients hd ny of t(4;4), t(4;), or del7p. Stndrd-risk ptients hd n bsence of high-risk bnormlities.

11 OS % surviving ptients 8 4 OS events 4 (4%) in 5 (2%) in 2 HR:.3 (95% CI: ) No. t risk Months Curves re beginning to seprte, but OS dt re immture Intent-to-tret popultion. Medin OS ws not reched; results did not cross the prespecified stopping boundry.

12 Summry of Efficcy Results: to 3 Prior Lines Subgroup PFS Medin, mo HR (95% CI) ORR, % CR, % VGPR, % MRD-negtive rtes, % 4 5 Time from lst line of tx to study tx: >2 months Medin, mo PFS HR (95% CI) ORR, % Time from lst line of tx to study tx: 2 months Medin, mo PFS HR (95% CI) ORR, % Refrctory to lst line of therpy Medin, mo PFS HR (95% CI) ORR, % NR.3 (.2-.49) NR.38 (.23-.3) 94 b NR.35 ( ) 9 NR.45 ( ) b 89 b NR OS HR (95% CI).9 (.4-.5) NR, not reched; tx, tretment. P <. for vs. b P <. for vs. 2

13 Hemtologic, % Most Common AEs (All Ptients): Updted Anlysis Neutropeni Febrile neutropeni (n = 283) (n = 28) All grde Grde 3/4 All grde Grde 3/4 25% 5% 25% 5% Anemi Thrombocytopeni Lymphopeni Nonhemtologic, % Dirrhe Ftigue Upper respirtory trct infection Cough 3 3 Constiption Muscle spsms Nsophryngitis 2 7 Nuse 25.4 Pneumoni No new sfety signls reported Common tretment-emergent AEs listed re either 25% ll grde OR 5% grde 3/4. 3

14 Conclusions significntly improved outcomes for ptients with myelom 3% reduction in risk of progression or deth for versus Similr findings observed cross ll nlyses in the to 3 prior lines popultion More ptients chieve deeper responses including MRD negtivity with is superior to regrdless of time since lst therpy, refrctoriness to lst line of therpy, or cytogenetic risk Sfety profile remins unchnged These dt support the use of for ptients who received prior therpy regrdless of risk sttus or refrctoriness to prior tretment 4

15 Acknowledgments Ptients who prticipted in this study Investigtors Dt nd sfety monitoring committee Stff members involved in dt collection nd nlyses Dvid Soong nd Christopher Vels 8 countries This study ws funded by Jnssen Reserch & Development, LLC Medicl writing nd editoril support were provided by Json Jung, PhD, of MedErgy, nd were funded by Jnssen Globl Services, LLC 5