Phase III IMvigor 010 Adjuvant Atezolizumab vs Observation

Phase III IMvigor 010: Adjuvant Atezolizumab vs Observation in Patients With High-Risk Muscle-Invasive Urothelial Cancer CCO Independent Conference Coverage* Highlights of the 2020 ASCO Virtual Scientific Meeting, May 29 -31, 2020 *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. This activity is provided by Clinical Care Options, LLC Supported by educational grants from Astra. Zeneca; Bayer Healthcare Pharmaceuticals, Inc. ; Bristol-Myers Squibb; Exelixis; and Pfizer and EMD Serono, Inc.

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Mvigor 010: Background § Standard of care for MIUC is radical surgery ± cisplatin neoadjuvant chemotherapy[1, 2] ‒ No conclusive level 1 evidence for efficacy of adjuvant chemotherapy ‒ 50% of patients ineligible for cisplatin therapy[3, 4] § Atezolizumab (anti–PD-L 1): immune checkpoint inhibitor ‒ Approved as monotherapy for locally advanced or metastatic UC[5] ‒ Unknown whether adjuvant atezolizumab would improve outcomes after radical surgery § Current study: primary analysis of phase III IMvigor 010 trial evaluating use of adjuvant atezolizumab vs observation in patients with high-risk MIUC[6] 1. AUA/SUO 2017 Guidelines. 2. EAU 2019 Guidelines. 3. Galsky. JCO. 2011; 29: 2432. 4. Koshkin. Clin Genitourin Cancer. 2018; 16: e 879. 5. Atezolizumab PI. 6. Hussain. ASCO 2020. Abstr 5000. Slide credit: clinicaloptions. com

IMvigor 010: Study Design § International, open-label, randomized phase III study Stratified by: number of resected LNs (< 10 vs ≥ 10), prior neoadjuvant (yes vs no), LN status (+ vs -), tumor stage (≤ p. T 2 vs p. T 3/p. T 4), PD-L 1 (IC 0/1 vs IC 2/3) Patients with high-risk MIUC (bladder, renal pelvis, ureter); ECOG 0 -2; radical cystectomy/ nephroureterectomy with LN dissection within ≤ 14 wks*; no radiation or adjuvant chemotherapy post surgery† (N = 809) Atezolizumab 1200 mg Q 3 W (16 cycles or 1 yr) (n = 406) Observation Alternating clinic visits/phone calls Q 3 W (n = 403) Disease recurrence/ survival follow-up Tumor assessment: Yrs 1 -3: every 12 wks Yrs 4 -5: every 24 wks Yr 6 *Upper tract UC staging eligibiity cirteria: For patients given neoadjuvant chemotherapy: yp. T 2 -T 4 a or yp. N+. For patients not given neoadjuvant chemotherapy: p. T 3 -T 4 a or p. N+. †To be enrolled, patients who were not given neoadjuvant chemotherapy also must have been ineligible or declined adjuvant cisplatin-based therapy. § Primary endpoint: DFS (ITT) Data cutoff: November 30, 2019 § Secondary endpoints: OS (ITT), safety; exploratory: biomarkers including PD-L 1 status Hussain. ASCO 2020. Abstr 5000. Slide credit: clinicaloptions. com

IMvigor 010: Baseline Characteristics Atezolizumab (n = 406) Observation (n = 403) 67 (31 -86) 66 (22 -88) Male, n (%) 322 (79) 316 (78) ECOG PS, n (%) § 0 § 1 § 2 248 (61) 142 (35) 16 (4) 259 (64) 130 (32) 14 (4) Primary tumor site, n (%) § Bladder § Upper tract (ureter, renal pelvis) 377 (93) 29 (7) 378 (94) 25 (6) Prior neoadjuvant chemotherapy, n (%) 196 (48) 189 (47) Characteristic Median age, yrs (range) Hussain. ASCO 2020. Abstr 5000. Atezolizumab (n = 406) Observation (n = 403) Pathologic tumor stage § p. T 2 N 0 § p. T 3 N 0 § p. T 4 N 0 34 (8) 124 (31) 32 (8) 39 (10) 119 (30) 33 (8) ≤ p. T 2 -4 and p. N+ 212 (52) 208 (52) PD-L 1 IHC status § IC 0 § IC 1 § IC 2 § IC 3 57 (14) 152 (37) 147 (36) 50 (12) 66 (16) 138 (34) 144 (36) 55 (14) Characteristic, n (%) Slide credit: clinicaloptions. com

IMvigor 010: Similar DFS With Adjuvant Atezolizumab vs Observation in High-Risk MIUC (ITT; Primary Endpoint) DFS Atezolizumab Observation 100 ++++ (n = 403) (n = 406) + ++ +++++ 208 (52) 212 (52) DFS events, n (%) + + + 80 16. 6 (11. 2 -24. 8) Median DFS, mos (95% CI) 19. 4 (15. 9 -24. 8) ++++++ 49 (44 -54) 51 (46 -56) ++++ 18 -mo DFS rate, % (95% CI) ++++++ 0. 89 (0. 74 -1. 08; P =. 2446) DFS HR (95% CI) ++++++ 60 ++++++ ++++ ++ ++++++++++++++ ++ + Atezolizumab ++++++++ +++ + + 40 +++ + Observation 20 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Mos Patients at Risk, n Atezolizumab 406 332 281 248 223 201 169 142 115 92 67 52 15 10 Observation 403 305 240 211 188 177 156 131 109 87 67 42 17 12 3 2 2 § No significant difference in DFS was observed in any clinical subgroup, including PD-L 1 expression level Hussain. ASCO 2020. Abstr 5000. Slide credit: clinicaloptions. com

IMvigor 010: OS With Adjuvant Atezolizumab vs Observation in High-Risk MIUC (ITT; Secondary Endpoint) Atezolizumab (n = 406) Observation (n = 403) OS 124 (31) 118 (29) OS events, n (%) 100 +++++++ Not reached Median OS, mos (95% CI) Not reached +++++++ 73 (69 -78) 79 (75 -83) 18 -mo OS rate, % (95% CI) +++++++++ OS HR (95% CI) 0. 85 (0. 66 -1. 09) 80 +++++++++++ +++++++++++++++++++++++ +++++++++++ ++ Atezolizumab 60 +++++ Observation 40 20 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 Mos Patients at Risk, n Atezolizumab 406 383 369 350 328 306 267 229 185 144 100 72 35 22 Observation 403 377 345 318 289 270 235 199 163 134 100 65 36 20 Hussain. ASCO 2020. Abstr 5000. 8 6 4 1 2 Slide credit: clinicaloptions. com

IMvigor 010: Safety Summary Atezolizumab (n = 390) Observation (n = 397) Any cause § Grade 3/4 § Grade 5 § Serious 368 (94) 145 (37) 7 (2) 122 (31) 313 (79) 80 (20) 8 (2) 71 (18) Treatment related § Grade 3/4 § Grade 5 § Serious 276 (71) 63 (16) 1 (< 1) 41 (11) NA Leading to d/c 61 (16) NA Leading to interruption 127 (33) NA AEs, n (%) Hussain. ASCO 2020. Abstr 5000. Grade 3/4 AEs of Special interest, n (%) Atezolizumab (n = 390) Observation (n = 397) 37 (9) 4 (1) Rash 7 (2) 0 Hepatitis (dx/labs) 9 (2) 2 (1) Hepatitis (labs) 5 (1) 2 (1) Infusion-related rx 2 (1) 0 Colitis 7 (2) 0 Pancreatitis 4 (1) 1 (< 1) Pneumonitis 2 (1) 0 Nephritis 3 (1) 0 All immune related Slide credit: clinicaloptions. com

IMvigor 010: Conclusions § Adjuvant atezolizumab monotherapy did not confer a benefit in DFS in patients with MIUC in a primary analysis of the IMvigor 010 trial ‒ No benefit seen in any subgroup evaluated, including higher PD-L 1 expression ‒ OS evaluation and exploratory analyses ongoing § Higher rates of immune-related AEs (primarily grade 1/2) and treatment discontinuation due to AEs observed with atezolizumab ‒ Safety profile consistent with known atezolizumab AEs Hussain. ASCO 2020. Abstr 5000. Slide credit: clinicaloptions. com

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