Results from IMpower-113 for extensive stage SCLC

Results from IMpower-113 for extensive stage SCLC

1. IMpower133: Addition of Atezolizumab to First-line Carboplatin/Etoposide in Extensive-Stage Small-Cell Lung Cancer Supported by educational grants from AbbVie, AstraZeneca, Genentech, and Takeda Oncology. Building a Bridge Between Science and Practice: CCO Independent Conference Highlights* from the 19th World Conference on Lung Cancer; September 23-26, 2018; Toronto, Canada *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.

2. Atezolizumab in ES-SCLC: Background Little progress in first-line treatment of ES-SCLC in past 20 yrs Standard of care remains platinum (carboplatin or cisplatin) plus etoposide [1-3] Patient outcomes remain poor, with a median OS of about 10 mos [3,4] Immune checkpoint inhibitors have shown clinical activity in refractory or metastatic SCLC [5-6] Nivolumab monotherapy approved as third-line treatment of metastatic SCLC [7] Preclinical data suggest possible synergy between anti–PD-L1 treatment and chemotherapy [8] IMpower133 evaluated the efficacy and safety of first-line atezolizumab (an anti–PD-L1 antibody) or placebo in combination with carboplatin and etoposide in ES-SCLC [9,10] References in slidenotes. Slide credit: clinicaloptions.com

3. IMpower133: Phase I/III Study of First-line Atezolizumab Plus Carboplatin/Etoposide in ES-SCLC Patients with ES-SCLC, ECOG PS 0/1, no prior systemic therapy for ES-SCLC (N = 403) Treatment until PD or loss of clinical benefit Atezolizumab 1200 mg on Day 1 Carboplatin AUC 5 on Day 1 Etoposide 100 mg/m 2 on Days 1-3 4 x 21-day cycles (n = 201) Placebo Carboplatin AUC 5 on Day 1 Etoposide 100 mg/m 2 on Days 1-3 4 x 21-day cycles (n = 202) Slide credit: clinicaloptions.com Stratified by treated asymptomatic brain metastases (yes vs no), sex (male vs female), ECOG PS (0 vs 1) Atezolizumab Placebo Induction Maintenance Co-primary endpoints: investigator-assessed PFS, OS Secondary endpoints: ORR, DoR, safety Liu SV, et al. WCLC 2018. Abstract PL02.07 . Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print] . Randomized, double-blind, placebo-controlled phase I/III trial

4. IMpower133: Baseline Patient Characteristics Characteristic Atezolizumab + Carboplatin/Etoposide (n = 201) Placebo + Carboplatin/Etoposide (n = 202) Median age, yrs (range) 64 (28-90) 64 (26-87) < 65 yrs, n (%) 111 (55) 106 (52) ≥ 65 yrs, n (%) 90 (45) 96 (48) Male, n (%) 129 (64) 132 (65) White, n (%) 163 (81) 159 (79) Asian, n (%) 33 (16) 36 (18) ECOG PS 0, n (%) 73 (36) 67 (33) ECOG PS 1, n (%) 128 (64) 135 (67) Current smoker, n (%) 74 (36.8) 75 (37.1) Former smoker, n (%) 118 (58.7) 126 (61.4) Brain metastases, n (%) 17 (8) 18 (9) Liver metastases, n (%) 77 (38) 72 (36) Slide credit: clinicaloptions.com Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print].

5. IMpower133: OS Slide credit: clinicaloptions.com Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print]. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Mos 100 80 60 40 20 OS (%) 12-month OS 51.7% 38.2% 12-mo OS Atezolizumab + CP/ET (n = 201) Placebo + CP/ET (n = 202) Median OS, mos (95% CI) 12.3 (10.8-15.9) 10.3 (9.3-11.3) HR (95% CI) 0.70 (0.54-0.91); P = .0069 Median follow-up, mos 13.9 Atezolizumab + CP/ET Placebo + CP/ET

6. IMpower133: PFS (Investigator Assessed) Slide credit: clinicaloptions.com Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print]. Atezolizumab + CP/ET (n = 201) Placebo + CP/ET (n = 202) Median PFS, mos (95% CI) 5.2 (4.4-5.6) 4.3 (4.2-4.5) HR (95% CI) 0.77 (0.62-0.96); P = .017 Median follow-up, mos 13.9 Atezolizumab + CP/ET Placebo + CP/ET 6 -mo PF S 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 100 80 60 40 20 12-mo PFS 30.9% 22.4% 5.4% 12.6% PFS (%) Mos

7. IMpower133: OS by Subgroup Slide credit: clinicaloptions.com Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print]. Median OS, Mos OS HR (95% CI) Population Atezolizumab + CP/ET Placebo + CP/ET Male (n = 261) 12.3 10.9 0.74 (0.54-1.02) Female (n = 142) 12.5 9.5 0.65 (0.42-1.00) < 65 yrs (n = 217) 12.1 11.5 0.92 (0.64-1.32) ≥ 65 yrs (n = 186) 12.5 9.6 0.53 (0.36, 0.77) ECOG PS 0 (n = 140) 16.6 12.4 0.79 (0.49-1.27) ECOG PS 1 (n = 263) 11.4 9.3 0.68 (0.50, 0.93) Brain metastases (n = 35) 8.5 9.7 1.07 (0.47-2.43) No brain metastases (n = 368) 12.6 10.4 0.68 (0.52-0.89) Liver metastases (n = 149) 9.3 7.8 0.81 (0.55-1.20) No liver metastases (n = 254) 16.8 11.2 0.64 (0.45-0.90) bTMB < 10 mut/mb (n = 139) 11.8 9.2 0.70 (0.45-1.07) bTMB ≥ 10 mut/mb (n = 212) 14.6 11.2 0.68 (0.47, 0.97) bTMB < 16 mut/mb (n = 271) 12.5 9.9 0.71 (0.52-0.98) bTMB ≥ 16 mut/mb (n = 80) 17.8 11.9 0.63 (0.35-1.15) ITT (N = 403) 12.3 10.3 0.70 (0.54-0.91) 0.1 1.0 2.5 Atezolizumab better Placebo better

8. IMpower133: ORR and DoR Slide credit: clinicaloptions.com Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print]. Atezolizumab + CP/ET (n = 121) Placebo + CP/ET (n = 130) Median DoR, mos (range) 4.2 (1.4-19.5) 3.9 (2.0-16.1) HR (95% CI) 0.70 (0.53-0.92) 6-mos EFS, % 32.2 17.1 12-mos EFS, % 14.9 6.2 Patients with ongoing response, n (%) 18 (14.9) 7 (5.4) CR CR/PR SD PD 70 60 50 40 20 Response (%) 30 10 2.5 1.0 60.2 64.4 20.9 21.3 10.9 6.9 Atezolizumab + CP/ET n = 201 Placebo +CP/ET n = 202

9. IMpower133: Safety Summary Characteristic, n (%) Atezolizumab + Carboplatin/Etoposide (n = 198) Placebo + Carboplatin/Etoposide (n = 196) Patients with ≥ 1 AE 198 (100) 189 (96.4) Grade 3 / 4 AEs 133 (67.2) 125 (63.8) Treatment-related AEs 188 (94.9) 181 (92.3) Serious AEs 74 (37.4) 68 (34.7) Immune-related AEs 79 (39.9) 48 (24.5) AEs leading to withdrawal from any treatment 22 (11.1) 6 (3.1) AEs leading to w/d from atezolizumab or placebo 21 (10.6) 5 (2.6) AEs leading to w/d from carboplatin 5 (2.5) 1 (0.5) AEs leading to w/d from etoposide 8 (4.0) 2 (1.0) Treatment-related deaths 3 (1.5) 3 (1.5) Slide credit: clinicaloptions.com Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print]. Median duration of treatment with atezolizumab: 4.7 mos (range: 0-21) Median received doses Atezolizumab: 7 (range: 1-30) Chemotherapy: 4 doses for carboplatin; 12 doses for etoposide (same for both treatment groups)

10. IMpower133: Most Frequent AEs AE, n (%) Atezolizumab + Carboplatin/Etoposide (n = 198) Placebo + Carboplatin/Etoposide (n = 196) Treatment-related AE Grade 1/2 Grade 3/4 Grade 5 Grade 1/2 Grade 3/4 Grade 5 Neutropenia 26 (13.1) 45 (22.7) 1 (0.5) 20 (10.2) 48 (24.5) Anemia 49 (24.7) 28 (14.1) 41 (20.9) 24 (12.2) Neutrophil count decreased 7 (3.5) 28 (14.1) 12 (6.1) 33 (16.8) Thrombocytopenia 12 (6.1) 20 (10.1) 14 (7.1) 15 (7.7) Leukopenia 15 (7.6) 10 (5.1) 10 (5.1) 8 (4.1) Febrile neutropenia 6 (3.0) 12 (6.1) Immune-related AE Grade 1/2 Grade 3/4 Grade 5 Grade 1/2 Grade 3/4 Grade 5 Rash 33 (16.7) 4 (2.0) 20 (10.2) Hepatitis 11 (5.6) 3 (1.5) 9 (4.6) Infusion-related reaction 7 (3.5) 4 (2.0) 9 (4.6) 1 (0.5) Pneumonitis 3 (1.5) 1 (0.5) 3 (1.5) 2 (1.0) Colitis 1 (0.5) 2 (1.0) Pancreatitis 1 (0.5) 2 (1.0) Slide credit: clinicaloptions.com Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print].

11. IMpower133: Conclusions Slide credit: clinicaloptions.com References in slidenotes. First-line therapy with atezolizumab + carboplatin/etoposide significantly improved OS and PFS vs carboplatin/etoposide alone [1,2] Median OS: 12.3 vs. 10.3 mos; HR: 0.70 ( P = .0069); 12-mo OS rate: 51.7% vs. 38.2% Median PFS: 5.2 vs. 4.3 mos; HR: 0.77 ( P = .017); 12-mo PFS rate: 12.6% vs. 5.4% No unexpected safety signals were reported Similar rates of hematologic AEs between treatment groups Chemotherapy delivery was not different between treatment groups irAE incidence and types were similar to those seen with atezolizumab monotherapy [3-5] The investigators suggest that atezolizumab + carboplatin/etoposide is a new standard of care for the first-line treatment of ES-SCLC [1,2]

12. clinicaloptions.com/oncology Go Online for More CCO Coverage of WCLC 2018! Capsule Summaries of all the key data Additional CME-certified analysis with expert faculty commentary on all the key studies studies