Hodgkin Lymphoma Nivolumab Anas Younes, M.D. Chief, Lymphoma - - PowerPoint PPT Presentation

Hodgkin Lymphoma

Nivolumab

New Drugs In Hematology October 1, 2018

Anas Younes, M.D. Chief, Lymphoma Service Memorial Sloan-Kettering Cancer Center

Nivolumab

• Clinical Activity
• Response Assessment
• Treatment Beyond Progression
• Flare

Progression-Free Survival by Best Overall Response

Number of patients at risk CR PR SD 16 21 8 40 128 47 40 126 44 33 89 25 32 71 19 27 46 11 20 25 8

0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 18 3 6 9 12 15 Probability of PFS PFS (months) 0.2 0.1 CR: 22 (19, NE) months PR: 15 (11, 19) months SD: 11 (6, 18) months

Nivolumab for Relapsed cHL

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017)

A Younes P Hilden B Coiffier A Hagenbeek G Salles W Wilson J.F. Seymour K Kelly J Gribben M Pfreunschuh F Morschhauser H Schoder A.D. Zelenetz J Rademaker R Advani N Valente C Fortpied T.E. Witzig L.H. Sehn A. Engert R.I. Fisher P-L Zinzani

• M. Federico M. Hutchings C. Bollard M. Trneny Y.A. Elsayed K Tobinai J.S.

Abramson N Fowler A Goy M Smith S Ansell J Kuruvilla M Dreyling C Thieblemont R.F. Little I Aurer M.H. J. Van Oers K Takeshita A Gopal S Rule S de Vos I Kloos M.S. Kaminski M Meignan L.H. Schwartz J.P. Leonard S.J. Schuster V.E. Seshan Ann Oncol, April 3, 2017 50 co-authors 38 Academic centers 4 Pharmaceutical companies 4 Imaging experts 3 statisticians

With the Exception of a CR, the depth of response has no impact on PFS

RECIL 2017

• 100
• 90
• 80
• 70
• 60
• 50
• 40
• 30
• 20
• 10

10 20 30 40 50 60 70

PD SD MR PR/CR

Younes A et al, Annals of Oncology 2017

Atypical Responses to Checkpoint Inhibitor Therapy

• In cHL, patients who have radiographic PD while on

chemotherapy do not benefit from continued treatment beyond PD

• In contrast, atypical response patterns including pseudo-

progression with checkpoint inhibitors led to clinical benefits in some patients with solid tumors who had been treated beyond PD

• A protocol amendment to the CheckMate 205 study (July 2014)

allowed patients with stable performance status and perceived clinical benefit to be treated beyond investigator-assessed disease progression (TBP) – Disease progression was classified into 3 categories (IWG 2007 criteria)

1) Increase in overall tumor burdena 3) Development of new lesionc 2) Non-target lesion growthb

Phase 2 CheckMate 205 Study Design

Cohort A BV naïve n = 63 Cohort B BV after auto-HCT n = 80 Cohort C BV before and/or after auto-HCT n = 100 Relapsed/refractory cHL after failure of auto-HCT N = 243 Nivolumab 3 mg/kg IV every 2 weeks Treatment until disease progression/unacceptable toxicity; patients could elect to discontinue and proceed to allogeneic (allo)-HCT Primary endpoint ORR by IRC in each cohort Patients with investigator-assessed progression could continue to receive treatment until further progression (≥10% greater increase in tumor burden)

Treatment beyond progressiona n = 70

Cohort A n = 19 Cohort B n = 23 Cohort C n = 28 Progression n = 105 Not treated beyond progression

n = 35

Prespecified exploratory endpoint Tumor burden change

Patient Demographics

Characteristic All patients N = 243 TBP n = 70 Non-TBP n = 35 Age, years 34 (18–72) 37 (18–72) 34 (23–63) Male, % 58 67 54 ECOG PS at baseline, % 1 54 46 61 39 34 66 Stage IV disease at initial diagnosis, % 27 27 17 Previous lines of therapy 4 (2–15) 3 (2–5) 4 (3–9) Time from diagnosis to first dose

• f nivolumab, years

4 (1–31) 6 (1–30) 3 (1–31) Time from first dose of nivolumab to initial progression date, months 6 (1–22) 7 (1–22) B symptoms at baseline, % 22 20 34 Bulky disease at baseline, % 20 19 23 Extra lymphatic involvement at baseline, % 43 46 51

Characteristics of Progressive Disease in Patients Treatment Beyond Progression (TBP)

Characteristics of progressive disease, n (%)a,b,c TBP n = 70 Non-TBP n = 35 Increase in overall tumor burdend 13 (19) 7 (20) Non-target lesion growthe 17 (24) 2 (6) Development of new lesionf 47 (67) 13 (37)

Best Overall Response (BOR) Prior to Initial Progression

Best overall response prior to progression, n (%) TBP n = 70 Non-TBP n = 35 Complete remission 5 (7) XX Partial remission 31 (44) XX Stable disease 20 (29) XX Progressive disease 13 (19) XX Non-evaluable 1 (1) XX

Change in Target Lesion Burden With Nivolumab TBP

Patients with target lesion reductions, n (%)a TBP n = 70 No reduction 24 (34) Any reduction 27 (39) >25% 16 (23) >50% 7 (10) 100% 1 (1)

Best overall response prior to initial progression:

51 patients were evaluable for post-progression tumor burden change at database lock

–100 –75 –50 –25 25 50 75 100 CR PR PD SD Patients (n = 51) Best reduction from first progression in target lesion tumor burden (%)

Time From Initial Progression to Next Therapy in Patients TBP

• 21/70 (30%) patients

remain on TBP at database lock

• The number of patients

TBP who discontinued due to disease progression was 39/70 (56%)

0.3 0.4 0.5 0.6 0.7 0.8 0.9 18

Time since first progression (months)

0.2 0.1 6 12 1.0 2 4 8 10 14 16

Probability of patients free of next treatment

35 13 TBP Number of patients at risk Non-TBP 3 1

TBP, median 8.8 (5.5, NE) months Non-TBP, median 1.5 (0.6, 3.3) months

20 35 70

Overall Survival

0.0 0.3 0.4 0.5 0.6 0.7 0.8 0.9 3 21 24 18

OS (months)

0.2 0.1 6 9 12 15 1.0

138 133 126 15 74

1 2 5 4 8 7 11 10 14 13 17 16 20 19 23 22

35 30 23 12 TBP 70 66 60 30 7

Probability of survival

Non-TBP PGF Number of patients at risk 1

PGF TBP Non-TBP

135 34 69 135 32 69 132 28 66 129 26 66 123 21 57 105 19 44 54 9 21 45 4 14

PGF, progression-free patients

Overall N = 243 PGF n = 138 TBP n = 70 Non-TBP n = 35

12-month OS, % (95% CI) 92 (88, 95) 96 (90, 98) 93 (83, 97) 80 (62, 90)

Summary of Nivo TBP in cHL

• In CheckMate 205, 70 of 105 (67%) eligible patients with

investigator-assessed disease progression were TBP – New lesions were the most common cause (67%) of progression in patients TBP

• Stable reductions in tumor burden were seen with continued

nivolumab treatment in patients TBP

• OS from first dose of study drug was 93% at 12 months for

patients TBP (vs 80% for non-TBP)

• Median time from progression to next therapy was 9 months for

patients TBP (vs 2 months for non-TBP)

Pt with relapsed FL 1st dose of Nivo 2/15/2016 at 10 a.m

2/15 2 PM 2/15 10 PM

Day 4 Day 10 Day 2

Pt with relapsed FL 1st dose of Nivo 2/15/2016 at 10 a.m