CheckMte 53: Rndomized Results of Continuous vs -Yer Fixed-Durtion Nivolumb in Ptients With Advnced Non-Smll Cell Lung Cncer Abstrct 297O Spigel DR, McCleod M, Hussein MA, Wterhouse DM, Einhorn L, Horn L, Creeln B, Bbu S, Leighl NB, Couture F, Chndler J, Goss G, Keogh G, Gron EB, Blnkstein KB, Dniel DB, Mohmed M, Li A, Anur N, Jotte R
Bckground Nivolumb is the stndrd of cre for previously treted NSCLC, demonstrting long-term survivl benefit, with 5-yer OS rte of 6% The mjority of nivolumb dt re bsed on tretment until PD or uncceptble toxicity Dt from phse I CheckMte 3 suggest tht ~2 yers of nivolumb monotherpy re sufficient for long-term clinicl benefit in ptients with previously treted NSCLC CheckMte 3 implemented stopping rule for nivolumb t 96 weeks 75% of ptients live >5 yers remined tretment- nd progression-free 25% of ptients live >5 yers stopped nivolumb erlier thn 96 weeks due to AEs Optiml durtion of tretment with PD-/PD-L inhibitors remins n importnt question CheckMte 53 is the first rndomized study to evlute tretment durtion with PD-/PD-L inhibitor Not mutully exclusive. Brhmer J, et l. Presented t: AACR Annul Meeting 27; April -5, 27; Wshington, DC. Abstrct 8356.
Study Design Key eligibility criteri: Advnced/ metsttic NSCLC prior systemic therpy ECOG PS -2 Treted CNS metstses llowed Nivolumb 3 mg/kg IV Q2W Continuous nivolumb R c Tretment for yer b Nivolumb Stop nivolumb retretment llowed t PD Explortory endpoints d : Sfety/efficcy e with continuous vs -yer tretment, efficcy, other (eg, biomrkers, PK) At dtbse lock (My 5, 27), minimum/medin follow-up time post-rndomiztion ws./4.9 months Conventionl systemic therpies, excluding immuno-oncology therpies. b Tretment until PD, uncceptble toxicity, or withdrwl of consent; tretment beyond investigtor-ssessed PD permitted. c All ptients on tretment t yer were rndomized regrdless of response sttus. d Primry endpoint ws incidence of high-grde select tretment-relted AEs.,2 e Responses were investigtor-ssessed every 8 weeks ± 5 dys from week 9. Hussein M, et l. Presented t: IASLC 6th World Conference on Lung Cncer; September 6-9, 25: Denver, Colordo. Abstrct ORAL2.2. 2. Wterhouse D, et l. J Clin Oncol. 26;34(suppl): Abstrct 359.
Ptient Flow nd Anlysis Popultions Efficcy nlyses Continuous nivolumb 76 hd response or SD t rndomiztion c 22 ptients on 245 ptients treted tretment t yer R b Stop nivolumb 87 hd response or SD t rndomiztion d Min US cohort 25 ptients discontinued prior to yer due to progression, deth, study withdrwl, toxicity, or other resons. b All 22 ptients continuing on tretment t yer were rndomized regrdless of response sttus. 57 of these 22 ptients hd PD nd were rndomized s llowed per protocol; sfety nlyses were bsed on ll 22 ptients, 7 in the continuous rm nd 3 in the stop rm. c 8 ptients discontinued tretment due to ptient request or withdrwl of consent. d 2 ptients discontinued tretment due to ptient request or withdrwl of consent
Bseline Ptient Chrcteristics (Efficcy Anlyses) Continuous tretment (n = 76) -yer tretment b (n = 87) Medin ge, yers (rnge) 7 yers, % 67 (5 92) 4 67 (49 86) 4 Femle, % 5 45 ECOG PS, c % - 2 9 8 95 2 Current or former/never smoker, % 96/4 97/3 Squmous histology, % 34 47 PD-L sttus, d % Quntifible <% e % e 5% e Prior lines of therpy, f % 2 3 4 4 33 28 26 29 CR or PR prior to rndomiztion, g % 7 56 53 32 68 28 6 25 75 23 Ptients who did not hve PD t rndomiztion. b With optionl retretment llowed t PD. c Not reported: Continuous, n =. yer, n = 2. d Using Dko PD-L IHC 28-8 phrmdx ssy. e Percentge of ptients with quntifible PD-L expression. f Not reported: Continuous, n = ; -yer, n = 3. g CRs: Continuous, n = 8; -yer, n = 2
PFS From Rndomiztion 8 Medin, Months (95% CI) PFS Rte, % 6-Month -Yer Continuous tx NR (NR) 8 65 -yer tx b.3 (6.4, 5.2) 69 4 HR:.42 (95% CI:.25,.7) PFS, % 6 4 2 3 6 9 2 5 8 2 24 Time Post-Rndomiztion, Months Number t risk Continuous tx 76 6 53 49 35 22 3 -yer tx 87 5 43 33 2 6 5 Ptients who did not hve PD t rndomiztion. minimum/medin follow-up time post-rndomiztion,./4.9 months. b With optionl retretment llowed t PD NR = not reched; tx = tretment
PFS From Rndomiztion by Response Sttus CR/PR SD Continuous tx -yer tx b,c Medin, Months (95% CI) NR (NR).6 (4.8, NA) Continuous tx Medin, Months (95% CI) NR (5.6, NA) -yer tx b 9.6 (4.5, 2.6) 8 HR:.45 (95% CI:.24,.85) 8 HR:.44 (95% CI:.7,.9) PFS, % 6 4 PFS, % 6 4 2 2 3 6 9 2 5 8 2 24 Number t risk Time Post-Rndomiztion, Months Continuous tx 53 45 4 39 28 7 7 2 -yer tx 49 29 26 2 4 3 3 6 9 2 5 8 2 24 Time Post-Rndomiztion, Months Number t risk Continuous tx -yer tx 23 5 2 7 5 3 38 2 7 3 7 5 2 Best overll response prior to rndomiztion; minimum/medin follow-up time post-rndomiztion,./4.9 months. b With optionl retretment llowed t PD. c Two ptients who stopped tretment hd CR prior to rndomiztion; both ptients lost CR (6 nd 3 months fter stopping tretment) with progression due to new lesions. NA = not vilble
PFS From Rndomiztion by Subgroup Overll 63.42 (.25,.7) <7 yers 7 yers n 97 66.28 (.3,.6).66 (.32,.37) ECOG PS - b 52.43 (.25,.73) Mle Femle 85 78.37 (.8,.74).56 (.25,.25) Former/current smoker c 57.42 (.25,.72) Squmous histology Non-squmous histology Second-line tretment Third-line tretment Fourth-/lter-line tretment/unknown <% PD-L expression % PD-L expression 5% PD-L expression PD-L not quntifible/not reported 67 96 66 49 48 26 66 23 7.4 (.8,.93).46 (.23,.92).34 (.4,.82).65 (.27,.56).35 (.3,.95).35 (.,.7).36 (.5,.86).5 (.3,.76).5 (.23,.2) HR (95% CI) 2 Fvors continuous tx Fvors stopping tx HR =.43 (95% CI:.25,.76) when djusted for gender, histology, best overll response, nd PD-L sttus using multivrite nlysis Ptients who did not hve PD t rndomiztion; minimum/medin follow-up time post-rndomiztion,./4.9 months. b HR not clculted for ptients with ECOG PS 2 due to smll smple size (n = 8); 3 ptients hd unreported ECOG PS. c HR not clculted for never-smokers/ptients with unknown smoking sttus due to smll smple size (n = 6)
OS From Rndomiztion 8 OS (%) 6 4 2 Medin, Months (95% CI) OS Rte, % 6-Month -Yer Continuous tx NR (NR) 97 88 -yer tx b 23.2 (23.2, NA) 95 8 HR:.63 (95% CI:.33,.2) Number t risk Continuous tx 76 -yer tx 87 3 6 9 2 5 8 2 24 27 Time Post-Rndomiztion, Months 74 72 67 62 4 29 7 2 79 74 7 6 38 23 4 Ptients who did not hve PD t rndomiztion; minimum/medin follow-up time post-rndomiztion,./4.9 months. b With optionl retretment llowed t PD
Retretment in -Yer Tretment Arm Efficcy nlyses Continuous nivolumb c 76 hd response or SD t rndomiztion 245 ptients treted 22 ptients on tretment t yer R b Stop nivolumb d 87 hd response or SD t rndomiztion 43 (49%) hd PD fter stopping nivolumb 34 (79%) were retreted with nivolumb Dt t time of nlysis (dtbse lock My 5, 27) Min US cohort; 25 ptients discontinued prior to yer due to progression, deth, study withdrwl, toxicity, or other resons. b All 22 ptients continuing on tretment t yer were rndomized regrdless of response sttus; 57 of these 22 ptients hd PD nd were rndomized s llowed per protocol; sfety nlyses were bsed on ll 22 ptients, 7 in the continuous rm nd 3 in the stop rm. c 8 ptients discontinued tretment due to ptient request or withdrwl of consent. d 2 ptients discontinued tretment due to ptient request or withdrwl of consent
Initition nd Durtion of Retretment Ptient 2 3 4 5 6 7 8 9 2 3 4 5 6 7 8 9 2 2 22 23 24 25 26 27 28 29 3 3 32 33 34 5 5 2 25 Time Since Rndomiztion, Months Off nivolumb tretment Nivolumb retretment Dt t time of nlysis (dtbse lock My 5, 27) Medin time between progression nd retretment:.6 months (rnge,.-4.9) Medin durtion of retretment: 3.8 months (rnge,.-7.5) Ptients who hd not died nd were not continuing retretment were in follow-up nd live s of dtbse lock PD Retretment ongoing Ptient died
Tumor Burden Chnge of Trget Lesions in Retreted Ptients Tumor burden chnge in trget lesions following retretment,b Type of PD n (%) Trget lesions only 2 (35) Nontrget lesions only (3) New lesions only 4 (4) Trget lesions nd new lesions 4 (2) Nontrget lesions nd new lesions (3) Trget lesions, nontrget lesions, nd new lesions 2 (6) Chnge in Trget Lesion Size From Rndomiztion, % 8 6 4 2 2 4 6 8 Strt of retretment % chnge truncted to % 2 3 4 5 Dys Since Rndomiztion Ptients with PD in trget lesions only. b n = : ptient without further ssessment fter retretment strt ws excluded
Subsequent Therpies Ptients, % Subsequent Therpy Continuous tretment (n = 76) -yer tretment b (n = 87) Any 2 37 Rdiotherpy 8 Surgery 7 6 Systemic therpy 3 29 Type of systemic therpy Post-study nivolumb Pclitxel Docetxel Crbopltin Gemcitbine Rmucirumb Erlotinib Investigtionl ntineoplstic Pembrolizumb Pemetrexed Other Investigtionl immunotherpy Other investigtionl gent 5 3 6 5 3 3 3 2 2 3 c Ptients who did not hve PD t rndomiztion. b With optionl retretment llowed t PD. c Etoposide, irinotecn, nd vinorelbine (n = ech)
Summry of Sfety Post-Rndomiztion Continuous tretment (n = 7) -yer tretment b (n = 3) Any grde, % Grde 3-4, % Any grde, % Grde 3-4, % Tretment-relted AEs 39 8 25 4 Tretment-relted SAEs 5 4 2 Select tretment-relted AEs 33 2 7 2 Tretment-relted AEs leding to discontinution 7 5 3 Few new-onset events occurred fter yer No tretment-relted deths were reported mong rndomized ptients No new sfety signls were observed All rndomized ptients. b AEs in this group include those during retretment
Summry CheckMte 53 is the first rndomized study to evlute durtion of therpy with PD-/PD-L inhibitor Among ptients still on nivolumb t yer, PFS ws significntly improved for those treted continuously vs stopping: PFS HR =.42 (95% CI:.25,.7) OS HR =.63 (95% CI:.33,.2), showing trend fvoring continuous nivolumb; follow-up for OS is ongoing The frequency of tretment-relted AEs ws numericlly higher with continuous vs -yer tretment, but overll, few new-onset events occurred fter yer