ECHELON-1: OS Analysis of First-line Brentuximab Vedotin + AVD vs ABVD in Advanced Classical - PowerPoint Presentation

1. ECHELON-1: OS Analysis of First-line Brentuximab Vedotin + AVD vs ABVD in Advanced Classical Hodgkin Lymphoma Supported by educational grants from AbbVie, AstraZeneca, Gilead Sciences Inc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, and Seattle Genetics.CCO Independent Conference Highlights*of the 2022 ASCO Annual Meeting, June 3-7, 2022, Chicago, Illinois*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.

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3. ECHELON-1 Updated Analysis: BackgroundABVD remains a standard-of-care treatment option for patients with advanced classical Hodgkin lymphoma1PET-guided approaches and BEACOPP-based treatments offer improved tolerability or disease control but have yet to show a significant improvement in OS2,3International, open-label phase III ECHELON-1 trial compared first-line treatment with brentuximab vedotin + AVD vs ABVD in patients with advanced cHLBrentuximab vedotin + AVD significantly improved PFS after 5 yr of follow-up (5-yr PFS rate: 82.2% vs 75.3%; P = .0017)4Current report presents a prespecified analysis of OS and updated analysis of efficacy and safety endpoints of the ECHELON-1 trial after ~6 yr of follow-up51. Connors. NEJM. 2018;378:331. 2. Mohty. Blood Cancer J. 2021;11:126. 3. Kreissl. Lancet Haematol. 2021;8:E398. 4. Straus. Lancet Haematol. 2021;8:e410. 5. Ansell. ASCO 2022. Abstr 7503.

4. ECHELON-1 Updated Analysis: Study DesignUpdated analysis of international, open-label phase III trial (data cutoff: June 1, 2021; median follow-up: 73 mo) Ansell. ASCO 2022. Abstr 7503. Connors. NEJM. 2018;378:331. NCT01712490.Adult with newly diagnosed Ann Arbor stage III/IV cHL; measurable disease; ECOG PS 0-2(N = 1334)Follow-up: every 3 mo for 36 mo, every 6 mo thereafterBrentuximab Vedotin + AVD* IV Days 1 and 15 of 6 x 28-day cycles(n = 664)ABVD† IV Days 1 and 15 of 6 x 28-day cycles(n = 670)End of cycle 2: PET scan (Deauville 5)EOT: CT/PET scan*BV + AVD: BV 1.2 mg/kg, doxorubicin 25 mg/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2. †ABVD: doxorubicin 25 mg/m2, bleomycin 10 U/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2.Primary endpoint: modified PFS per independent review2-yr PFS rate with BV + AVD vs ABVD: 82.1% vs 77.2% (HR: 0.77; 95% CI: 0.60-0.98; P = .04)Current analysisKey secondary endpoint: α-controlled, event-driven OS analysisLTFU assessments: OS for PET2+ vs PET2- patients; investigator-assessed PFS; subsequent tx; safety

5. ECHELON-1 Updated Analysis: Baseline CharacteristicsAnsell. ASCO 2022. Abstr 7503.Characteristic, n (%)BV + AVD (n = 664)ABVD (n = 670)Total (N = 1334)Male378 (57)398 (59)776 (58)Median age, yr (IQR)Aged <60 yr, n (%)Aged ≥60 yr, n (%)35 (26-51)580 (87)84 (13)37 (27-53)568 (85)102 (15)36 (26-52)1148 (86)186 (14)Ann Arbor stage at diagnosisStage IIStage IIIStage IVNA/unknown/missing1 (<1)237 (36)425 (64)1 (<1)0246 (37)421 (63)3 (<1)1 (<1)483 (36)846 (64)4 (<1)IPS0-12-34-7142 (21)355 (53)167 (25)141 (21)357 (53)172 (26)283 (21)712 (53)339 (25)PET2 statusPositiveNegativeUnknown/unavailable47 (7)588 (89)29 (4)58 (9)578 (86)34 (5)105 (8)1166 (87)63 (5)

6. ECHELON-1 Updated Analysis: OS and PFSAddition of brentuximab vedotin to AVD significantly reduced risk of death by 41% vs ABVD (HR: 0.59; 95% CI: 0.40-0.88; log-rank P = .009), with median OS not reachedComparable OS benefit observed in multivariate analysis adjusting for baseline disease and demographic characteristics (HR: 0.53; 95% CI: 0.34-0.83)Covariates most strongly associated with OS: age, non-white race, ECOG PS, PET2 statusAcross subgroups defined by baseline disease and demographic factors, OS benefit was generally consistent with brentuximab vedotin + AVD BV + AVD significantly reduced risk of progression or death by 32% vs ABVD (HR: 0.68; 95% CI: 0.53-0.86; log-rank P = .002)Ansell. ASCO 2022. Abstr 7503.OS OutcomeBV + AVD (n = 664)ABVD (n = 670)OS events, n3964Estimated 6-yr OS, % (95% CI)93.9 (91.6-95.5)89.4 (86.6-91.7)PFS OutcomeBV + AVD (n = 664)ABVD (n = 670)PFS events, n112159Estimated 6-yr PFS, % (95% CI)82.3 (79.1-85.0)74.5 (70.8-77.7)

7. ECHELON-1 Updated Analysis: Cause of Death per Investigator, Second MalignanciesAmong patients who died:BV + AVD: PD (not always cause of death), n = 19; received subsequent therapy, n = 18ABVD: PD, n = 28; received subsequent therapy, n = 25; received subsequent BV, n = 13Numerically fewer second malignancies in BV + AVD arm vs ABVD arm: BV + AVD arm, n = 23 (hematologic, n = 9; solid tumors, n =14); ABVD arm, n = 32 (hematologic, n = 17; solid tumors, n = 14)Among those with second malignancies, n = 2 on each arm received transplant and n = 3 on ABVD arm had prior radiationAnsell. ASCO 2022. Abstr 7503.Cause of Death per InvestigatorBV + AVD(n = 662)ABVD(n = 659)Total deaths, n (%)HL or complications, nSecond malignancies, n39 (5.9)32164 (9.7)4511Other causes, nUnknownAccident/suicideCOVID-19Heart failureIntracranial hemorrhageLower respiratory tract infection613011085*01101*n = 2 died of indeterminate cause following investigator-documented PD.

8. ECHELON-1 Updated Analysis: Subsequent TherapyNumerically lower rate of subsequent therapy with BV + AVD vs ABVDAnsell. ASCO 2022. Abstr 7503.Subsequent Therapy, n (%)BV + AVD (n = 662)ABVD (n = 659)Total (N = 1321)Patients with ≥1 subsequent anticancer tx135 (20) 157 (24) 292 (22)BV or CT regimensBV monotherapyBV + CTRadiationCT + radiationHigh-dose CT + transplantAllogeneic transplantImmunotherapy*BV + nivolumabNivolumabPembrolizumabNivolumab combinationsOther78 (12)8 (1)2 (<1)54 (8)1 (<1)44 (7)4 (<1)18 (3)015 (2)2 (<1)1 (<1)0108 (16)49 (7)20 (3)54 (8)4 (<1)59 (9)12 (2)24 (4)4 (<1)18 (3)6 (<1)1 (<1)1 (<1) 186 (14)57 (4)22 (2)108 (8)5 (<1)103 (8)16 (1)42 (3)4 (<1)33 (2)8 (<1)2 (<1)1 (<1)*Predominantly based on anti–PD-1 agents.

9. ECHELON-1 Updated Analysis: Pregnancy, Peripheral NeuropathyHigher PN rate after 2 yr of follow-up with BV + AVD (67%) vs ABVD (43%)Among those with PN on BV + AVD vs ABVD, 86% vs 87% resolved/continued to improve after 6 yr of follow-upMedian time to resolution: 16 vs 10 wkNo formal assessment of fertility performedFor BV + AVD vs ABVD arms, 113 vs 78 pregnancies reported among patients and their partnersAmong female patients: pregnancies, 49 vs 28; live births, 56 vs 23Among partners of male patients: 33 vs 33; live births, 40 vs 36No stillbirths reportedAnsell. ASCO 2022. Abstr 7503.Grade of PN, n (%)BV + AVD(n = 662)ABVD(n = 659)Ongoing PN at last follow-up125 (19)59 (9)Grade 171 (11)39 (6)Grade 238 (6)16 (2)Grade 3*15 (2)4 (<1)Grade 4*1 (<1)0*Those who were lost to follow-up or died before resolution/improvement not censored: BV + AVD arm, 11/16; A +AVD arm, 4/4.

10. ECHELON-1 Updated Analysis: ConclusionsIn this updated analysis of the phase III ECHELON-1 trial after ~6 yr of follow-up, a prespecified analysis demonstrated significantly improved OS among patients with advanced cHL treated with first-line BV + AVD vs ABVDHR: 0.59; 95% CI: 0.40-0.88; log-rank P = .009OS improved despite high rate of subsequent therapy use in ABVD arm (24% vs 20% with BV + AVD)BV + AVD associated with fewer second malignancies, less PD, and fewer disease-related deaths vs ABVD Investigators concluded that BV + AVD should be considered as a preferred first-line treatment option for patients with untreated stage III or IV cHLAnsell. ASCO 2022. Abstr 7503.

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