TUMORI DEL POLMONE IMMUNOTERAPIA

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1 TUMORI DEL POLMONE IMMUNOTERAPIA Andrea Botticelli Sapienza Università di Roma

2 Dove eravamo rimasti NEL 2017

3 E NEI PAZ PD-L1 < 50 %????

4 KEYNOTE-042 Study Design

5 PFS 5,4 mo PFS 7 mo

6 OS 16 mo

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8 COME MIGLIORARE LA RISPOSTA ALL IMMUNOTERAPIA?

9 IMMUNO + CHT KN 189, 407 IMP 132,131 IMP 150 IMMUNO + TARGET COMBO IMMUNO CK 227

10 IMMUNO + CHT KN 189, 407 IMP 132,131

11 CHT + IMMUNO ADK SQ

12 P F S, % ADK PFS mo rate 34.1% 17.3% Median (95% CI) 8.8 mo ( ) 4.9 mo ( ) PFS: HR 0.52 [95% CI: ]; p < N o. a t R is k M o n th s

13 ADK OS

14 ADK PFS PFS 10.8!!!

15 ADK OS

16 SQ PFS

17 SQ OS

18 SQ PFS PFS 10.1!!!

19 SQ OS

20 IMMUNO + CHT KN 189, 407 IMP 132,131 IMP 150 IMMUNO + TARGET COMBO IMMUNO CK 227

21 IMP 150 IMMUNO + TARGET

22 CHT + IMMUNO + TARGET

23 CHT + IMMUNO + TARGET vs CHT + TARGET PFS OS

24 CHT + IMMUNO vs CHT + TARGET

25 IMMUNO + CHT KN 189, 407 IMP 132,131 IMP 150 IMMUNO + TARGET COMBO IMMUNO CK 227

26 COMBO IMMUNO CK 227

27 CHECKMATE 227 Patients for PD-L1 co-primary analysis N = 1189 Nivolumab 3 mg/kg Q2W Ipilimumab 1 mg/kg Q6W n = 396 Nivolumab + ipilimumab n = 396 1% PD-L1 expression R 1:1:1 Histology-based chemotherapy b n = 397 Chemotherapy b n = 397 Key Eligibility Criteria Stage IV or recurrent NSCLC No prior systemic therapy No known sensitizing EGFR/ALK alterations ECOG PS 0 1 Nivolumab 240 mg Q2W n = 396 Patients for TMB co-primary analysis c Nivolumab + ipilimumab n = 139 Chemotherapy b n = 160 Stratified by SQ vs NSQ N = 550 <1% PD-L1 expression R 1:1:1 Nivolumab 3 mg/kg Q2W Ipilimumab 1 mg/kg Q6W n = 187 Histology-based chemotherapy b n = 186 Nivolumab 360 mg Q3W + histology-based chemotherapy b n = 177 Co-primary endpoints: Nivolumab + ipilimumab vs chemotherapy OS in PD-L1 selected populations PFS in TMB-selected populations Database lock: January 24, 2018; minimum follow-up: 11.2 months a NCT b NSQ: pemetrexed + cisplatin or carboplatin, Q3W for 4 cycles, with optional pemetrexed maintenance following chemotherapy or nivolumab + pemetrexed maintenance following nivolumab + chemotherapy; SQ: gemcitabine + cisplatin, or gemcitabine + carboplatin, Q3W for 4 cycles; c The TMB co-primary analysis was conducted in the subset of patients randomized to nivolumab + ipilimumab or chemotherapy who had evaluable TMB 10 mut/mb 7

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29 QUANDO TMB ALTO COMBO-IMMUNO!! INDIP DA :

30 CHECKMATE 227 PART 1 STUDY DESIGN N = 1189 Nivolumab 3 mg/kg Q2W Ipilimumab 1 mg/kg Q6W n = 396 1% PD-L1 expression R 1:1:1 Histology-based chemotherapy a n = 397 Key eligibility criteria Stage IV or recurrent NSCLC No prior systemic therapy No known sensitizing EGFR/ALK alterations ECOG PS 0 1 Stratified by SQ vs NSQ N = 550 Nivolumab 240 mg Q2W n = 396 Nivolumab 3 mg/kg Q2W Ipilimumab 1 mg/kg Q6W n = 187 <1% PD-L1 expression b R 1:1:1 Histology-based chemotherapy a n = 186 Nivolumab 360 mg Q3W + histology-based chemotherapy a n = 177 Secondary endpoint: Nivolumab + chemotherapy vs chemotherapy PFS c in patients with <1% tumor PD-L1 expression Co-primary endpoints: OS in PD-L1 selected populations and PFS c in TMB-selected populations treated with nivolumab + ipilimumab vs chemotherapy Database lock: January 24, 2018; minimum follow-up: 11.2 months a NSQ: pemetrexed + cisplatin or carboplatin, Q3W for 4 cycles, with optional pemetrexed maintenance following chemotherapy or nivolumab + pemetrexed maintenance following nivolumab + chemotherapy; SQ: gemcitabine + cisplatin, or gemcitabine + carboplatin, Q3W for 4 cycles; b One patient was randomized with <1% tumor PD-L1 expression in IVRS, but was subsequently found to have 1% tumor 30 PD-L1 expression; c Per BICR

31 SOLO NEL TMB ALTO!!! NIVO + CHT

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33 TMB and PD-L1

34 TMB indipendente da PD-L1

35 LIMITI DEL TMB :

36 SCLC

37 NUOVI ORIZZONTI TRATTAMENTO BIOMARCATORI

38 TERAPIA ADOTTIVA Durgeau, Frontiers In Immunology 2018

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41 NUOVI ORIZZONTI BIOMARCATORI

42 CHI È IL MICROBIOTA? Insieme di batteri e altri microorganismi ( funghi, protozoi, virus ) All'interno del corpo umano, si stima che ci siano 10 volte più cellule microbiche delle cellule umane. ( ) specie (main phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria)

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44 COME MIGLIORARE LA RISPOSTA ALL IMMUNOTERAPIA? TRATTAMENTO BIOMARCATORI NUOVE COMBINAZIONI/SEQUENZE : EFFETTO IMMUNOLOGICO-IMMUNO- PROFILO NUOVE STRATEGIE

45 Thanks for your attention