0.4 a. 0.4 (1S ffl > 0.2 -~ 0.2 -~ :::, :::, Cl') 0.0 Cl') 0.0 0 6 12 18 24 30 0 6 12 18 24 30 Survival Time (months) Survival Time (months) I I I I I I I I I I 16 Other 58 (13.2%) 23 (10.4%) Stage at Entrya IIIb/IV 18.0%/82.0% 21.2%/78.8% Histology (%) Nonsquamous NSCLCb325 (73.7%) 156 (70.3%) Adenocarcinoma 222 (50.3%) 106 (47.7%) Large cell 10 (2.3%) 10 (4.5%) Otherc93 (21.1%) 40 (18.0%) Squamous 116 (26.3%) 66 (29.7%) ECOG PSd 0/1 40.1%/59.9% 38.3%/61.7% Smoking Historye Ever/never smoker 74.1%/25.9% 71.5%/28.5% Time from start of induction therapy to study randomization (months) Median (range) 3.25 (1.6-4.8) 3.29 (2.7-5.1) aStage at Entry was not reported for all randomized patients. Percentages are representative of N=440 for the ALIMTA arm and N=222 for the placebo arm. bIncludes patients with adenocarcinoma, large cell, and other histologic diagnoses. cThe subgroup of “Other” represents patients with a primary diagnosis of NSCLC whose disease did not clearly qualify as adenocarcinoma, large cell carcinoma, or squamous cell carcinoma. dEastern Cooperative Oncology Group Performance Status (ECOG PS) was not reported for all randomized patients. Percentages are representative of N=439 for the ALIMTA arm, and N=222 for the placebo arm. eSmoking history was not reported for all randomized patients. Percentages are representative of N=437 for the ALIMTA arm and N=221 for the placebo arm. Patients received a median of 5 cycles of ALIMTA and 3.5 cycles of placebo. Patients randomized to ALIMTA received a relative dose intensity of 95.7%. A total of 213 patients (48.3%) completed ൒6 cycles and a total of 98 patients (22.6%) completed ൒10 cycles of treatment with ALIMTA. In the overall study population, ALIMTA was statistically superior to placebo in terms of overall survival (OS) (median 13.4 months versus 10.6 months , HR=0.79 (95% CI: 0.65-0.95), p-value=0.012) and PFS (median 4.0 months versus 2.0 months, HR=0.60 (95% CI: 0.49-0.73), p-value<0.00001). A difference in treatment outcomes was observed according to histologic classification. For the population of patients with nonsquamous NSCLC, ALIMTA was superior to placebo for OS (median 15.5 months versus 10.3 mont hs, HR=0.70 (95% CI: 0.56-0.88)) and PFS (median 4.4 months versus 1.8 months, HR=0.47 (95% CI: 0.37-0.60)). For the population of patients with squamous NSCLC, ALIMTA did not improve OS compared to placebo (median 9.9 months versus 10.8 months, HR=1.07 (95% CI: 0.77-1.50)) or PFS (median 2.4 months versus 2.5 months, HR=1.03 (95% CI: 0.71-1.49)). This difference in treatment effect for ALIMTA based on histology demonstrating lack of benefit in squamous cell histology was also observed in the first-line and second-line studies. [see Clinical Studies (14.1, 14.3)] Efficacy results for the overall patient population are presented in Table 13 and Figure 3, and efficacy results by pre-specifie d histologic subgroups are presented in Table 14 and Figure 4, below. Table 13: Maintenance Therapy: Efficacy of ALIMTA versus Placebo in NSCLC - ITT Population Efficacy Parameter a,b ALIMTA (N=441)Placebo (N=222) Median overall survivalc(95% CI) 13.4 mos (11.9 -15.9) 10.6 mo s (8.7-12.0) Hazard ratio (HR)c(95% CI) 0.79 (0.65-0.95) p-value p=0.012 Median progression-free survival (95% CI) 4.0 mos (3.1-4.4) 2.0 mos (1.5-2.8) Hazard ratio (HR)c(95% CI) 0.60 (0.49-0.73) p-value p<0.00001 aPFS and OS were calculated from time of randomization, after completion of 4 cycles of induction platinum-based chemotherapy. bValues for PFS given based on independent review (A LIMTA N=387, Placebo N=194). cUnadjusted hazard ratios are provided. A HR <1.0 indicates that the result is better in the ALIMTA arm than in the placebo arm. Table 14: Maintenance Therapy: Efficacy in NSCLC by Histologic Subgroupsa Overall Survival Progression-Free Survivalb ALIMTA Placebo ALIMTA Placebo Median (months) Median (months) Median (months) Median (months) HRc(95% CI) HRc(95% CI)Protocol ADU-CL-02-v8Aduro Biotech, Inc. CRS-207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 100 17 Nonsquamous NSCLCd15.5 10.3 4.4 1.8 N=481 0.70 (0.56-0.88) 0.47 (0.37-0.60) Adenocarcinoma 16.8 11.5 4.6 2.7 N=328 0.73 (0.56-0.96) 0.51 (0.38-0.68) Large cell carcinoma 8.4 7.9 4.5 1.5 N=20 0.98 (0.36-2.65) 0.40 (0.12-1.29) Othere11.3 7.7 4.1 1.6 N=133 0.61 (0.40-0.94) 0.44 (0.28-0.68) Squamous cell 9.9 10.8 2.4 2.5 N=182 1.07 (0.77-1.50) 1.03 (0.71-1.49) aPFS and OS were calculated from time of randomization, after completion of 4 cycles of induction platinum-based chemotherapy. All results unadjusted for multiple comparisons.