A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)

Brief summary public domain (ClinicalTrials.gov)

A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with locally advanced unresectable or metastatic G/GEJ cancer (hereafter referred to as gastric cancer) and esophageal cancer. Two cohorts of patients with gastric cancer have been enrolled in parallel in this study: the second-line (2L) Gastric Cancer Cohort consists of patients with gastric cancer who have progressed after receiving a platinum-containing or fluoropyrimide-containing chemotherapy regimen in the first-line setting, and the first-line (1L) Gastric Cancer Cohort consists of patients with gastric cancer who have not received prior chemotherapy in this setting. In each cohort, eligible patients will be assigned to one of several treatment arms. Additionally, a cohort of patients with esophageal cancer who have not received prior systemic treatment for their disease will be enrolled in this study. Eligible patients will be randomized to chemotherapy or the combination of chemotherapy with checkpoint inhibitor immunotherapy.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to RECIST v1.1 [From randomization up to approximately 84.2 months]. Number, percentage of participants (95% Confidence Interval). Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib (n=5): 40.0 (5.27 to 85.34); Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) (n=12): 16.7 (2.09 to 48.41); Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 0 (0.00 to 24.71); Stage 1 Cohort 2: Atezolizumab + BL-8040 (n=13): 15.4 (1.92 to 45.45); Stage 1 Cohort 2: Atezolizumab + Linagliptin (n=14): 21.4 (4.66 to 50.80); Stage 1: Cisplatin + 5-FU (Control) (n=23): 47.8 (26.82 to 69.41); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=65): 53.8 (41.03 to 66.30); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=62): 67.7 (54.66 to 79.06). Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + PEGPH20: Difference in Overall Response Rates -16.67 (95% CI -45.77 to 12.43); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + BL-8040: Difference in Overall Response Rates -1.28 (95% CI -38.09 to 35.53); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + Linagliptin: Difference in Overall Response Rates 4.76 (95% CI -33.09 to 42.61); superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Progression Free Survival (PFS) After Randomization, as Determined by Investigator According to RECIST v1.1 [From randomization to the first occurrence of PD or death (up to approximately 84.2 months)]. Median, months (95% Confidence Interval). Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib (n=5): 14.93 (10.64 to NA) [Upper limit of 95% confidence interval (CI) was not estimable due to insufficient number of participants with events.]; Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) (n=12): 6.06 (3.68 to 8.77); Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 1.84 (1.48 to 2.10); Stage 1 Cohort 2: Atezolizumab + BL-8040 (n=13): 1.97 (1.71 to 7.92); Stage 1 Cohort 2: Atezolizumab + Linagliptin (n=14): 1.95 (1.64 to 4.93); Stage 1: Cisplatin + 5-FU (Control) (n=23): 5.98 (2.69 to 8.11); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=65): 7.03 (5.55 to 8.28); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=62): 6.90 (5.95 to 9.89). Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + PEGPH20: Hazard Ratio (HR) 6.74 (95% CI 2.06 to 22.00); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + BL-8040: Hazard Ratio (HR) 0.97 (95% CI 0.41 to 2.27); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + Linagliptin: Hazard Ratio (HR) 1.31 (95% CI 0.58 to 2.97); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab + Cisplatin + 5-FU: Hazard Ratio (HR) 0.79 (95% CI 0.48 to 1.31); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU: Hazard Ratio (HR) 0.56 (95% CI 0.33 to 0.94); superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Overall Survival (OS) After Randomization [From randomization to death (up to approximately 84.2 months)]. Median, months (95% Confidence Interval). Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib (n=5): 16.99 (14.65 to NA) [Upper limit of 95% CI was not estimable due to insufficient number of participants with events.]; Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) (n=12): 8.33 (6.37 to 10.94); Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 7.00 (5.26 to 8.87); Stage 1 Cohort 2: Atezolizumab + BL-8040 (n=13): 10.64 (3.71 to 39.06); Stage 1 Cohort 2: Atezolizumab + Linagliptin (n=14): 8.57 (4.27 to 28.12); Stage 1: Cisplatin + 5-FU (Control) (n=23): 10.09 (7.59 to 23.20); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=65): 12.98 (11.17 to 15.70); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=62): 16.56 (12.22 to 21.03). Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + PEGPH20: Hazard Ratio (HR) 1.16 (95% CI 0.52 to 2.61); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + BL-8040: Hazard Ratio (HR) 0.63 (95% CI 0.26 to 1.51); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + Linagliptin: Hazard Ratio (HR) 0.60 (95% CI 0.25 to 1.43); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab + Cisplatin + 5-FU: Hazard Ratio (HR) 0.99 (95% CI 0.58 to 1.68); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU: Hazard Ratio (HR) 0.75 (95% CI 0.43 to 1.29); superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: OS at Month 6 and Month 12 [At Months 6 and 12]. Number, percentage of participants (95% Confidence Interval). Month 6: Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib (n=4): 100.00 (100.00 to 100.00); Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) (n=9): 75.00 (50.50 to 99.50); Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=7): 53.85 (26.75 to 80.95); Stage 1 Cohort 2: Atezolizumab + BL-8040 (n=6): 51.28 (23.10 to 79.47); Stage 1 Cohort 2: Atezolizumab + Linagliptin (n=7): 56.25 (29.80 to 82.70); Stage 1: Cisplatin + 5-FU (Control) (n=17): 78.02 (60.98 to 95.06); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=56): 87.52 (79.43 to 95.61); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=54): 88.65 (80.73 to 96.57). Month 12: Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib (n=4): 100.00 (100.00 to 100.00); Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) (n=9): 25.00 (0.50 to 49.50); Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=7): 23.08 (0.17 to 45.98); Stage 1 Cohort 2: Atezolizumab + BL-8040 (n=6): 42.74 (14.71 to 70.76); Stage 1 Cohort 2: Atezolizumab + Linagliptin (n=7): 40.18 (13.51 to 66.85); Stage 1: Cisplatin + 5-FU (Control) (n=17): 36.71 (16.54 to 56.89); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=56): 57.83 (45.73 to 69.92); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=54): 65.36 (53.36 to 77.36). Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + PEGPH20: Difference in Event-free Rate -21.15 (95% CI -57.69 to 15.38); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + PEGPH20: Difference in Event-free Rate -1.92 (95% CI -35.46 to 31.61); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + BL-8040: Difference in Event-free Rate -23.72 (95% CI -61.06 to 13.63); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + BL-8040: Difference in Event-free Rate 17.74 (95% CI -19.49 to 54.96); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + Linagliptin: Difference in Event-free Rate -18.75 (95% CI -54.80 to 17.30); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + Linagliptin: Difference in Event-free Rate 15.18 (95% CI -21.03 to 51.39); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab + Cisplatin + 5-FU: Difference in Event-free Rate 9.50 (95% CI -9.36 to 28.37); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab + Cisplatin + 5-FU: Difference in Event-free Rate 21.11 (95% CI -2.41 to 44.64); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU: Difference in Event-free Rate 10.63 (95% CI -8.16 to 29.42); superiority. Analysis

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 [Up to approximately 84.2 months]. Median, months (95% Confidence Interval). Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib (n=2): NA (NA to NA) [Median and 95% CI were not estimable due to insufficient number of participants with events.]; Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) (n=2): 3.32 (2.89 to 3.75); Stage 1 Cohort 2: Atezolizumab + BL-8040 (n=2): NA (58.84 to NA) [Median and upper limit of 95% CI were not estimable due to insufficient number of participants with events.]; Stage 1 Cohort 2: Atezolizumab + Linagliptin (n=3): 14.46 (3.55 to NA) [Upper limit of 95% CI was not estimable due to insufficient number of participants with events.]; Stage 1: Cisplatin + 5-FU (Control) (n=11): 5.91 (2.83 to 14.06); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=35): 6.90 (5.32 to 8.77); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=42): 7.16 (4.40 to 15.31). Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + Linagliptin: Hazard Ratio (HR) 0.24 (95% CI 0.02 to 2.67); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab + Cisplatin + 5-FU: Hazard Ratio (HR) 0.85 (95% CI 0.41 to 1.76); superiority. Analysis, Stage 1: Cisplatin + 5-FU (Control) vs Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU: Hazard Ratio (HR) 0.57 (95% CI 0.27 to 1.19); superiority. Analysis, Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) vs Stage 1 Cohort 2: Atezolizumab + BL-8040: Hazard Ratio (HR) 0.009 (95% CI 0.00 to NA); superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 [Up to approximately 84.2 months]. Number, percentage of participants (95% Confidence Interval). Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib (n=5): 80.0 (28.36 to 99.49); Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) (n=12): 66.7 (34.89 to 90.08); Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 0 (0.00 to 24.71); Stage 1 Cohort 2: Atezolizumab + BL-8040 (n=13): 23.1 (5.04 to 53.81); Stage 1 Cohort 2: Atezolizumab + Linagliptin (n=14): 21.4 (4.66 to 50.80); Stage 1: Cisplatin + 5-FU (Control) (n=23): 56.5 (34.49 to 76.81); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=65): 78.5 (66.51 to 87.69); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=62): 83.9 (72.33 to 91.98).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stages 1 and 2: Percentage of Participants With Adverse Events (AEs) [Stage 1: Up to 84.2 months; Stage 2: Up to 42.6 months]. Number, percentage of participants. Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib (n=5): 100; Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) (n=12): 100; Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 100; Stage 1 Cohort 2: Atezolizumab + BL-8040 (n=13): 100; Stage 1 Cohort 2: Atezolizumab + Linagliptin (n=14): 100; Stage 1: Cisplatin + 5-FU (Control) (n=23): 100; Stage 1: Atezolizumab + Cisplatin + 5-FU (n=65): 100; Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=62): 100; Stage 2: Atezolizumab + Tiragolumab (n=14): 100.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Serum Concentration of Atezolizumab [Pre-dose, 30 minutes (min) post-dose (infusion=60 min) on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20, 24, & 28; Stage 1 treatment discontinuation (TD) (up to approximately 82.7 months)]. Geometric Mean, micrograms per milliliter (μg/mL) (Geometric Coefficient of Variation). Pre-dose on Day 1 of Cycle 1: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): NA (NA) [Geometric Mean (GM) and Geometric Coefficient of Variation were not estimable as the values were below the level of quantification.]; Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): NA (NA) [GM and Geometric Coefficient of Variation were not estimable as the values were below the level of quantification.]; Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): NA (NA) [GM and Geometric Coefficient of Variation were not estimable as the values were below the level of quantification.]. 30 min post-dose on Day 1 of Cycle 1: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 362 (39.2); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 375 (21.6); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 379 (22.2). Pre-dose on Day 1 of Cycle 2: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 64.4 (28.0); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 70.9 (48.8); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 60.8 (43.9). Pre-dose on Day 1 of Cycle 3: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 95.6 (37.2); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 113 (54.3); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 87.3 (77.3). Pre-dose on Day 1 of Cycle 4: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 117 (NA) [Geometric Coefficient of Variation was not estimable for 1 participant.]; Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 137 (47.6); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 108 (56.8). Pre-dose on Day 1 of Cycle 8: Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 216 (37.1); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 185 (44.6). Pre-dose on Day 1 of Cycle 12: Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 204 (29.1); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 159 (46.7). Pre-dose on Day 1 of Cycle 16: Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 289 (29.2); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 206 (34.2). Pre-dose on Day 1 of Cycle 20: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 273 (15.5). Pre-dose on Day 1 of Cycle 24: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 239 (35.1). Pre-dose on Day 1 of Cycle 28: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 209 (NA) [Geometric Coefficient of Variation was not estimable for 1 participant.]. Stage 1 TD: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=13): 93.7 (58.5); Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 195 (55.9); Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=44): 89.8 (130.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Serum Concentration of Tiragolumab [Pre-dose, 30 min post-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20, 24, & 28 (1 Cycle=28 days); Stage 1 TD (up to approximately 46.7 months)]. Geometric Mean, μg/mL (Geometric Coefficient of Variation). Pre-dose on Day 1 of Cycle 1: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): NA (NA) [GM and Geometric Coefficient of Variation were not estimable because the values were below the level of quantification.]. 30 min post-dose on Day 1 of Cycle 1: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 223 (20.8). Pre-dose on Day 1 of Cycle 2: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 31.4 (45.6). Pre-dose on Day 1 of Cycle 3: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 43.3 (85.1). Pre-dose on Day 1 of Cycle 4: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 50.5 (62.1). Pre-dose on Day 1 of Cycle 8: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 83.4 (39.1). Pre-dose on Day 1 of Cycle 12: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 76.1 (58.2). Pre-dose on Day 1 of Cycle 16: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 87.6 (30.9). Pre-dose on Day 1 of Cycle 20: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 102 (15.9). Pre-dose on Day 1 of Cycle 24: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 97.8 (38.3). Pre-dose on Day 1 of Cycle 28: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 90.0 (NA) [Geometric Coefficient of Variation was not estimable for 1 participant.]. Stage 1 TD: Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 39.8 (166.4).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Plasma Concentration of PEGPH20 [Pre-dose: Day 1 of Cycles 1, 2, 3, 4 & Days 8, 15 of Cycle 1; 5 minutes & 1-3 hours post-dose: Day 1 Cycle 1; 5 min post-dose: Day 1 Cycle 2; Stage 1: TD (up to approx 3.3 months) & Day 120 post last dose of atezo (up to approx 6.8 months)]. Geometric Mean, μg/mL (Geometric Coefficient of Variation). Pre-dose on Day 1 of Cycle 1: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): NA (NA) [GM and geometric coefficient of variation were not estimable because the values were below the level of detection.]. 5 min post-dose on Day 1 of Cycle 1: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 31.4 (1290.5). 1-3 h post-dose on Day 1 of Cycle 1: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 25.8 (1086.5). Pre-dose on Day 8 of Cycle 1: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 0.529 (NA) [As the number of evaluable samples available for analysis was less than 3, the geometric coefficient of variation was not calculated.]. Pre-dose on Day 15 of Cycle 1: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 0.485 (NA) [As the number of evaluable samples available for analysis was less than 3, the geometric coefficient of variation was not calculated.]. Pre-dose on Day 1 of Cycle 2: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 0.647 (NA) [As the number of evaluable samples available for analysis was less than 3, the geometric coefficient of variation was not calculated.]. 5 min post-dose on Day 1 of Cycle 2: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 56.3 (42.8). Pre-dose on Day 1 of Cycle 3: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 1.92 (1992.5). Pre-dose on Day 1 of Cycle 4: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 10.2 (NA) [Geometric coefficient of variation was not estimable for 1 participant.]. Stage 1 TD: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 2.12 (1276.5). Stage 1 Day 120 post last dose: Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=12): 0.0375 (NA) [As the number of evaluable samples available for analysis was less than 3, the geometric coefficient of variation was not calculated.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Atezolizumab [Up to approximately 82.7 months]. Count Of Participants, Participants. Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=10): 3; Stage 1: Atezolizumab + Cisplatin + 5-FU (n=39): 5; Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 8.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Number of Participants With Treatment-emergent ADAs to Tiragolumab [Up to approximately 46.7 months]. Count Of Participants, Participants. Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU (n=43): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Stage 1: Number of Participants With Treatment-emergent ADAs to PEGPH20 [Up to approximately 3.3 months]. Count Of Participants, Participants. Stage 1 Cohort 2: Atezolizumab + PEGPH20 (n=10): 0.