bValues for PFS are given based on independent review (ALIMTA N=387, Pl acebo 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. A HR >1.0 indicates that the result is better in the placebo arm than in the ALIMTA arm. dIncludes patients with adenocarcinoma, large cell carcinoma, and other histology. eThe 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. Figure 3: Kaplan-Meier Curve for Overall Survival ALIM TA (A) versus Placebo (P) in NSCLC - ITT Population.Protocol ADU-CL-02-v8Aduro Biotech, Inc. CRS-207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 101:c cu .c e a. co > - ~ :::, Cl) 1.0 Median (95% Cl) 0.9 - ALIMTA 13.4 (11.9, 15.9) 0.8 -- Placebo 10.6 (8.7, 12.0) 0.7 Unadjusted HR (95% Cl) :0 0.6 cu 0.79 (0.65, 0.95) .0 e 0.5 a. cu 0.4 > -~ 0.3 :::s Cl) 0.2 0.1 0.0 0 6 12 18 24 30 36 42 Patients at Risk Survival Time (months) A p 1.0 0.8 0.6 0.4 0.2 0.0 441 340 221 141 63 222 160 93 60 29 29 13 11 4 0 0 Nonsquamous NSCLC Squamous Cell NSCLC 1.0 -AUMTA 0.8 -ALIMTA -- Placebo :c -- Placebo as 0.6 .c e a. 0.4 co > 0.2 -~ :::, Cl) 0.0 0 6 12 18 24 30 36 42 0 6 12 18 24 30 36 42 Survival Time (months) Survival Time (months) 18 Figure 4: Kaplan-Meier Curves for Overall Survival ALIMTA versus Placebo in NSCLC - Nonsquamous NSCLC and Squamous Cell NSCLC. 14.3 Non-Small Cell Lung Ca ncer - After Prior Chemotherapy A multi-center, randomized, open label study was conducted in pa tients with Stage III or IV NSCLC after prior chemotherapy to compare the overall survival following treatment with ALIMTA versus docetaxel. ALIMTA was administered intravenously over 10 minutes at a dose of 500 mg/m2and docetaxel was administered at 75 mg/m2as a 1-hour intravenous infusion. Both drugs were given on Day 1 of each 21-day cycle. All patients treated with ALIMTA received vitamin supplementation with folic acid and vitamin B 12. The study was intended to show either an overall survival superiority or non-inferiority of ALIMTA to docetaxel. Patient demographics of the intent to treat (ITT) population are shown in Table 15. Table 15: Second-Line Therapy: Summary of Patient Characteristics in NSCLC Study Patient characteristicALIMTA (N=283)Docetaxel (N=288) Age (yrs) Median (range) 59 (22-81) 57 (28-87) Gender (%) Male/Female 68.6/31.4 75.3/24.7 Stage at Entry (%) III/IV 25.1/74.9 25.3/74.7 Diagnosis/Histology (%) Adenocarcinoma 154 (54.4) 142 (49.3) Squamous 78 (27.6) 94 (32.6) Bronchoalveolar 4 (1.4) 1 (0.3) Other 47 (16.6) 51 (17.7) Performance Status (%)a 0-1 234 (88.6) 240 (87.6) 2 30 (11.4) 34 (12.4) aPerformance status was not reported for all randomized patients. Percentages are representative of N=264 for the ALIMTA arm and N=274 for the docetaxel arm. The primary endpoint in this study was overall survival. The median survival time was 8.3 months in the ALIMTA treatment arm and 7.9 months in the docetaxel arm, with a hazard ratio of 0.99 (see Table 16). The study did not show an overall survival superiority of ALIMTA. Table 16: Efficacy of ALIMTA versus Docetaxel in Non-Small Cell Lung Cancer - ITT Population ALIMTA (N=283)Docetaxel (N=288) Median overall survival (95% CI) 8.3 mos (7.0-9.4) 7.9 mos (6.3-9.2) Hazard ratio (HR) (95% CI) 0.99 (0.82-1.20) Median progression-free survival (95% CI) 2.9 mos (2.4-3.1) 2.9 mos (2.7-3.4) Hazard ratio (HR) (95% CI) 0.97 (0.82-1.16) Overall response rate (95% CI) 8.5% (5.2-11.7) 8.3% (5.1-11.5) A retrospective analysis of the impact of NSCLC histology on overall survival was examined. Clinically relevant differences in survival according to histology were observed and are shown in Table 17. This difference in treatment effect for ALIMTA based on histology demonstrating a lack of efficacy in squamous cell histology was also observed in the first-line combination study and in the maintenance study [see Clinical Studies (14.1, 14.2)] . Table 17: Second-Line Therapy: Overall Survival of ALIMTA versus Docetaxel in NSCLC by Histologic Subgroups Histology SubgroupMedian Overall Survival in Months (95% CI)Unadjusted Hazard Ratio (HR)a,b (95% CI)Adjusted Hazard Ratio (HR)a,b,c (95% CI)ALIMTA Docetaxel Nonsquamous NSCLCd (N=399)9.3 (7.8-9.7)N=205 8.0 (6.3-9.3)N=194 0.89 (0.71-1.13)0.78 (0.61-1.00) Adenocarcinoma (N=301)9.0 (7.6-9.6)N=158 9.2 (7.5-11.3)N=143 1.09 (0.83-1.44)0.92 (0.69-1.22) Large Cell 12.8 N=18 4.5 N=29 0.38 0.27Protocol ADU-CL-02-v8Aduro Biotech, Inc. CRS-207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 102 19 (N=47) (5.8-14.0) (2.3-9.1) (0.18-0.78) (0.11-0.63) Othere (N=51)9.4 (6.0-10.1)N=29 7.9 (4.0-8.9)N=22 0.62 (0.32-1.23)0.57 (0.27-1.20) Squamous Cell (N=172)6.2 (4.9-8.0)N=78 7.4 (5.6-9.5)N=94 1.32 (0.93-1.86)1.56 (1.08-2.26) aA HR that is less than 1.0 indicates that survival is better in the ALIMTA arm than in the docetaxel arm. Alternatively, a HR tha t is greater than 1.0 indicates survival is better in the docetaxel arm than in the ALIMTA arm. bUnadjusted for multiple comparisons. cHRs adjusted for ECOG PS, time since prior chemotherapy, disease stage, and gender. dIncludes adenocarcinoma, large cell, and other histologies except those with squamous cell type. eThe subgroup of “other” represents patients with a primary diagnosis of NSCLC whose disease did not clearly qualify as adenocarcinoma, squamous cell carcinoma, or large cell carcinoma. 14.4 Malig nant Pleural Mesothelioma A multi-center, randomized, single-blind study in 448 chemonaive patients with malignant pleural mesothelioma (MPM) compared survival in patients treated with ALIMTA in combination with cisplatin to survival in patients receiving cisplatin alo ne. ALIMTA was administered intravenously over 10 minutes at a dose of 500 mg/m2and cisplatin was administered intravenously over 2 hours at a dose of 75 mg/m2beginning approximately 30 minutes after the end of administration of ALIMTA. Both drugs were given on Day 1 of each 21-day cycle. After 117 patients were treated, white cell and GI toxicity led to a change in protocol where by all patients were given folic acid and vitamin B 12supplementation. The primary analysis of this study was performed on the population of all patients randomly assigned to treatment who received study drug (randomized and treated). An analysis was also performed on patients who received folic acid and vitamin B 12 supplementation during the entire course of study therapy (fully supplemented), as supplementation is recommended [see Dosage and Administration (2.3)] . Results in all patients and those fully supplemented were similar.