Safety and Efficacy Study of AMG 820 and Pembrolizumab Combination in Select Advanced Solid Tumor Cancer

Brief summary public domain (ClinicalTrials.gov)

A multi-center Phase 1b/2 study testing the combination of AMG 820 and pembrolizumab in subjects with select advanced solid tumors.

Detailed description public domain (ClinicalTrials.gov)

Phase 1b is AMG 820 dose determining and aimed at assessing the safety and tolerability of the selected starting dose of AMG 820 in combination with pembrolizumab. Phase 2 of the study will further evaluate safety and tolerability and additionally test whether AMG 820 can enhance the anti-tumor activity observed historically with pembrolizumab alone and/or overcome lack of response to pembrolizumab monotherapy in subjects with select solid tumors.

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

Participants With Dose Limiting Toxicities (DLT) [The DLT evaluation period was Day 1 to Day 21]. Count Of Participants, Participants. Participants with treatment emergent DLTs: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 0; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 1; Part 2, Group 1: CRC MMR-proficient (n=41): 3; Part 2, Group 2: Pancreatic Cancer (n=31): 2; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 1; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 0. DLT: Autoimmune pancreatitis: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 0; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 1; Part 2, Group 1: CRC MMR-proficient (n=41): 0; Part 2, Group 2: Pancreatic Cancer (n=31): 0; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 0; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 0. DLT: Autoimmune hepatitis: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 0; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 1; Part 2, Group 1: CRC MMR-proficient (n=41): 0; Part 2, Group 2: Pancreatic Cancer (n=31): 0; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 0; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 0. DLT: Cholecystitis: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 0; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 1; Part 2, Group 1: CRC MMR-proficient (n=41): 0; Part 2, Group 2: Pancreatic Cancer (n=31): 0; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 0; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 0. DLT: Electrolyte imbalance: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 0; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 1; Part 2, Group 1: CRC MMR-proficient (n=41): 0; Part 2, Group 2: Pancreatic Cancer (n=31): 0; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 0; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 0. DLT: Fatigue: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 0; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 0; Part 2, Group 1: CRC MMR-proficient (n=41): 1; Part 2, Group 2: Pancreatic Cancer (n=31): 0; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 0; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 0. DLT: Aspartate aminotransferase increased: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 0; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 0; Part 2, Group 1: CRC MMR-proficient (n=41): 1; Part 2, Group 2: Pancreatic Cancer (n=31): 1; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low

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

Participants With Treatment -Emergent Adverse Events (TEAEs) [Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2]. Count Of Participants, Participants. >=1 TEAE: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 8; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 7; Part 2, Group 1: CRC MMR-proficient (n=41): 41; Part 2, Group 2: Pancreatic Cancer (n=31): 31; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 4; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 19; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 6. Grade >=3: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 7; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 7; Part 2, Group 1: CRC MMR-proficient (n=41): 40; Part 2, Group 2: Pancreatic Cancer (n=31): 30; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 4; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 19; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 6. Grade >=4: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 2; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 4; Part 2, Group 1: CRC MMR-proficient (n=41): 24; Part 2, Group 2: Pancreatic Cancer (n=31): 26; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 2; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 12; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 4. Grade >=5: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): NA [investigator misunderstanding of meaning]; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): NA [investigator misunderstanding of meaning]; Part 2, Group 1: CRC MMR-proficient (n=41): NA [investigator misunderstanding of meaning]; Part 2, Group 2: Pancreatic Cancer (n=31): NA [investigator misunderstanding of meaning]; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): NA [investigator misunderstanding of meaning]; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): NA [investigator misunderstanding of meaning]; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): NA [investigator misunderstanding of meaning]. Serious AE: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 5; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 2; Part 2, Group 1: CRC MMR-proficient (n=41): 31; Part 2, Group 2: Pancreatic Cancer (n=31): 23; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 3; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 11; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 5. Leading to interruption of AMG 820: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 4; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 3; Part 2, Group 1: CRC MMR-proficient (n=41): 23; Part 2, Group 2: Pancreatic Cancer (n=31): 7; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 1; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 7; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 2. Leading to discontinuation AMG 820: Part 1, Cohort 2: AMG 820 1100 mg + P

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

Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment [Day 1 up to 207 days for Part 1; Day 1 up to 572 days for Part 2]. Count Of Participants, Participants. >=1 TEAE: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 5; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 7; Part 2, Group 1: CRC MMR-proficient (n=41): 41; Part 2, Group 2: Pancreatic Cancer (n=31): 25; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 4; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 14; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 6. Grade >=3: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 3; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 5; Part 2, Group 1: CRC MMR-proficient (n=41): 28; Part 2, Group 2: Pancreatic Cancer (n=31): 11; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 1; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 10; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 6. Grade >=4: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 1; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 1; Part 2, Group 1: CRC MMR-proficient (n=41): 5; Part 2, Group 2: Pancreatic Cancer (n=31): 5; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 2; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 2. Grade >=5: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): NA [investigator misunderstanding of meaning]; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): NA [investigator misunderstanding of meaning]; Part 2, Group 1: CRC MMR-proficient (n=41): NA [investigator misunderstanding of meaning]; Part 2, Group 2: Pancreatic Cancer (n=31): NA [investigator misunderstanding of meaning]; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): NA [investigator misunderstanding of meaning]; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): NA [investigator misunderstanding of meaning]; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): NA [investigator misunderstanding of meaning]. Serious AE: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 2; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 2; Part 2, Group 1: CRC MMR-proficient (n=41): 12; Part 2, Group 2: Pancreatic Cancer (n=31): 4; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 3; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 3. Leading to interruption of AMG 820: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 2; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 3; Part 2, Group 1: CRC MMR-proficient (n=41): 16; Part 2, Group 2: Pancreatic Cancer (n=31): 7; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 5; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 2. Leading to discontinuation AMG 820: Part 1, Cohort 2

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

Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment [Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2]. Count Of Participants, Participants. >=1 TEAE: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 5; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 7; Part 2, Group 1: CRC MMR-proficient (n=41): 39; Part 2, Group 2: Pancreatic Cancer (n=31): 24; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 4; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 13; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 6. Grade >=3: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 2; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 5; Part 2, Group 1: CRC MMR-proficient (n=41): 29; Part 2, Group 2: Pancreatic Cancer (n=31): 9; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 1; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 10; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 4. Grade >=4: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 1; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 1; Part 2, Group 1: CRC MMR-proficient (n=41): 5; Part 2, Group 2: Pancreatic Cancer (n=31): 4; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 2; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 2. Grade >=5: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): NA [investigator misunderstanding of meaning]; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): NA [investigator misunderstanding of meaning]; Part 2, Group 1: CRC MMR-proficient (n=41): NA [investigator misunderstanding of meaning]; Part 2, Group 2: Pancreatic Cancer (n=31): NA [investigator misunderstanding of meaning]; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): NA [investigator misunderstanding of meaning]; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): NA [investigator misunderstanding of meaning]; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): NA [investigator misunderstanding of meaning]. Serious AE: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 2; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 2; Part 2, Group 1: CRC MMR-proficient (n=41): 16; Part 2, Group 2: Pancreatic Cancer (n=31): 5; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 3; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 4. Leading to interruption of PEM: Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg (n=8): 1; Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg (n=7): 3; Part 2, Group 1: CRC MMR-proficient (n=41): 15; Part 2, Group 2: Pancreatic Cancer (n=31): 6; Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0; Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 5; Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 2. Leading to discontinuation AMG 820: Part 1, Coho

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

Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) [Baseline: Day -28; Treatment: up to Month 13.7]. Number, percentage of participants (95% Confidence Interval). Part 1: AMG 820 + Pem (n=15): 0.0 (0.00 to 0.00); Part 2, Group 1: CRC MMR-proficient (n=41): 4.9 (0.60 to 16.53); Part 2, Group 2: Pancreatic Cancer (n=31): 0.0 (0.0 to 0.0); Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0.0 (0.0 to 0.0); Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 5.3 (0.13 to 26.03); Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 0.0 (0.0 to 0.0).

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Time to Response (TTR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) For Participants Who Responded [Day 1 up to Month 16 (max time to censoring)]. Mean, month (Full Range). Part 2, Group 1: CRC MMR-proficient (n=2): 2.1587 (2.004 to 2.168); Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=1): 2.0698 (NA to NA) [with a single participant contributing data, the full range values equal the observed value.].

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Time to Progression (TTP) for Participants Who Had Progressive Disease [Day 1 up to 14.4 months (max time to censoring)]. Mean, month (Full Range). Part 1: AMG 820 + Pem (n=10): 2.1865 (0.460 to 5.552); Part 2, Group 1: CRC MMR-proficient (n=29): 3.0691 (0.559 to 8.411); Part 2, Group 2: Pancreatic Cancer (n=13): 2.3878 (0.296 to 4.698); Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=3): 4.6762 (2.070 to 6.604); Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=8): 6.0863 (1.150 to 11.992); Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=4): 7.7864 (1.938 to 13.667).

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Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12 [Day 1 up to Month 6 or Month 12]. Number, percentage of participants (90% Confidence Interval). Month 6: Part 1: AMG 820 + Pem 200 mg (n=15): 59.077 (32.25 to 78.28); Part 2, Group 1: CRC MMR-proficient (n=41): 53.915 (40.00 to 63.93); Part 2, Group 2: Pancreatic Cancer (n=31): 16.705 (7.40 to 29.24); Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 75.000 (22.34 to 94.63); Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 52.105 (31.91 to 68.93); Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 41.667 (9.26 to 72.47). Month 12: Part 1: AMG 820 + Pem 200 mg (n=15): 47.262 (21.19 to 69.63); Part 2, Group 1: CRC MMR-proficient (n=41): 38.963 (25.77 to 51.94); Part 2, Group 2: Pancreatic Cancer (n=31): 8.353 (2.22 to 19.81); Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 25.00 (2.08 to 60.89); Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 34.737 (17.37 to 52.79); Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 41.667 (9.26 to 72.47).

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Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and Month 12 [Day 1 up to Month 6 or Month 12]. Number, percentage of participants (90% Confidence Interval). Month 6: Part 1: AMG 820 + Pem 200 mg (n=15): 10.476 (1.23 to 31.40); Part 2, Group 1: CRC MMR-proficient (n=41): 13.490 (5.99 to 24.04); Part 2, Group 2: Pancreatic Cancer (n=31): 0.000 (0.00 to 0.00); Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 25.000 (2.08 to 60.89); Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 26.471 (10.67 to 45.41); Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 33.333 (7.37 to 62.95). Month 12: Part 1: AMG 820 + Pem 200 mg (n=15): 0.000 (0.00 to 0.00); Part 2, Group 1: CRC MMR-proficient (n=41): 5.396 (1.36 to 13.77); Part 2, Group 2: Pancreatic Cancer (n=31): 0.000 (0.00 to 0.00); Part 2, Group 3: NSCLC PD-L1 Low, Naïve (n=4): 0.000 (0.00 to 0.00); Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low (n=19): 6.618 (0.77 to 21.97); Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High (n=6): 33.333 (7.37 to 62.95).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2 [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Median, hour (Full Range). Cycle 1: AMG 820 1100 mg (n=97): 2.0 (1.0 to 170); AMG 820 1400 mg (n=18): 2.0 (1.0 to 7.0). Cycle 2: AMG 820 1100 mg (n=97): 3.00 (1.00 to 25.0); AMG 820 1400 mg (n=18): 2.00 (1.00 to 25.0).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Maximum Observed Drug Concentration (Cmax) During Treatment Cycles 1 + 2 [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Geometric Mean, ug/mL (Geometric Coefficient of Variation). Cycle 1: AMG 820 1100 mg (n=97): 331 (27); AMG 820 1400 mg (n=18): 485 (23). Cycle 2: AMG 820 1100 mg (n=97): 363 (32); AMG 820 1400 mg (n=18): 536 (21).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Last (AUClast) During Treatment Cycles 1 + 2 [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Geometric Mean, hr*ug/mL (Geometric Coefficient of Variation). Cycle 1: AMG 820 1100 mg (n=97): 55100 (37); AMG 820 1400 mg (n=18): 80400 (33). Cycle 2: AMG 820 1100 mg (n=97): 55200 (38); AMG 820 1400 mg (n=18): 73500 (45).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Over the Dose Interval (AUCtau) During Treatment Cycles 1 + 2 [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Geometric Mean, hr*ug/mL (Geometric Coefficient of Variation). Cycle 1: AMG 820 1100 mg (n=97): 59300 (33); AMG 820 1400 mg (n=18): 90000 (29). Cycle 2: AMG 820 1100 mg (n=97): 75400 (35); AMG 820 1400 mg (n=18): 114000 (31).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Minimum Observed Drug Concentration (Cmin) During Treatment Cycles 1 + 2 [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Geometric Mean, ug/mL (Geometric Coefficient of Variation). Cycle 1: AMG 820 1100 mg (n=97): 49.9 (51); AMG 820 1400 mg (n=18): 90.9 (35). Cycle 2: AMG 820 1100 mg (n=97): 78.7 (66); AMG 820 1400 mg (n=18): 199 (34).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Terminal Elimination Half-life (t1/2z) During Treatment Cycles 1 + 2 [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Geometric Mean, hour (Geometric Coefficient of Variation). Cycle 1: AMG 820 1100 mg (n=97): 217 (26); AMG 820 1400 mg (n=18): 214 (24). Cycle 2: AMG 820 1100 mg (n=97): 170 (16).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Volume of Distribution (Vz) During Treatment Cycles 1 + 2 [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Geometric Mean, liter (Geometric Coefficient of Variation). Cycle 1: AMG 820 1100 mg (n=97): 5200 (35); AMG 820 1400 mg (n=18): 4110 (25). Cycle 2: AMG 820 1100 mg (n=97): 4560 (21).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Drug Clearance (CL) During Treatment Cycles 1 + 2 [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Geometric Mean, liter/hour (Geometric Coefficient of Variation). Cycle 1: AMG 820 1100 mg (n=97): 16.6 (37); AMG 820 1400 mg (n=18): 13.3 (33). Cycle 2: AMG 820 1100 mg (n=97): 18.6 (30).

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AMG 820 Pharmacokinetic Parameter by Dose Group: Accumulation Ratio (AR) [Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36]. Geometric Mean, ratio (Geometric Coefficient of Variation). AMG 820 1100 mg (n=97): 1.23 (18); AMG 820 1400 mg (n=18): 1.25 (16).