Safety and Efficacy Study of AMG 820 and Pembrolizumab Combination in Select Advanced Solid Tumor Cancer
Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT02713529
Collaborator
Merck Sharp & Dohme LLC (Industry)
117
15
1
37.1
7.8
0.2
Study Details
Study Description
Brief Summary
A multi-center Phase 1b/2 study testing the combination of AMG 820 and pembrolizumab in subjects with select advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
117 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase1b/2 Study Assessing Safety and Anti-tumor Activity of AMG 820 in Combination With Pembrolizumab in Select Advanced Solid Tumors
Actual Study Start Date
:
Apr 14, 2016
Actual Primary Completion Date
:
Jan 2, 2019
Actual Study Completion Date
:
May 17, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AMG820 and pembrolizumab Treatment with AMG820 and pembrolizumab |
Biological: AMG820 and pembrolizumab
Treatment with AMG820 and pembrolizumab
|
Outcome Measures
Primary Outcome Measures
- Participants With Dose Limiting Toxicities (DLT) [The DLT evaluation period was Day 1 to Day 21]
DLTs were evaluated by the Dose Level Review Team (DLRT). A DLT was defined as any grade >=3 adverse event occurring during a DLT time window (21 day period from the initial administration of AMG 820 and pembrolizumab in combination), and if judged by the investigator to be related to the administration of AMG 820 and/or pembrolizumab.
- 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]
TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.
- 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]
TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.
- 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]
TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.
- Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) [Baseline: Day -28; Treatment: up to Month 13.7]
ORR was defined as the percentage of participants with a best overall response of complete response or partial response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). During treatment radiographic imaging was performed at Week 10 and repeated at least every 10 weeks until disease progression. Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required.
Secondary Outcome Measures
- 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)]
Time to response was defined as the time from first dose of AMG 820 until first documented complete or partial response per irRECIST divided by 365.25 days/12.
- Time to Progression (TTP) for Participants Who Had Progressive Disease [Day 1 up to 14.4 months (max time to censoring)]
Time to progression was defined as the time from first dose of AMG 820 until first documented progressive disease per irRECIST divided by 365.25 days/12.
- Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12 [Day 1 up to Month 6 or Month 12]
Overall survival time was calculated as the number of days from the first administration of AMG 820 to date of death or censoring divided by (365.25/12). Data are reported as the percentage of participants who were alive at Month 6 and Month 12.
- 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]
Progression-free survival time was calculated as the number of days from the first administration of AMG 820 to date of progressive disease or death or censoring divided by (365.25/12). Data are reported as the percentage of participants who were alive and progression-free at Month 6 and Month 12.
- 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]
- 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]
- 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]
AUClast is the area under the serum concentration-time curve from time zero to time of last quantifiable concentration.
- 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]
AUCtau is the area under the serum concentration-time curve over the dose interval tau, with tau equal to 21 days.
- 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]
- 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]
- 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]
Volume of distribution observed at terminal phase after intravenous dosing.
- 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]
Drug clearance observed after intravenous dosing.
- 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]
Accumulation ratio is AUCtau following administration in Cycle 2 / AUCtau after administration in Cycle 1
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Pathologically documented, advanced colorectal, pancreatic or non-small cell lung cancer that is refractory to standard treatment, or the subjects have been intolerant to or refuse standard treatment.
-
Measurable disease per RECIST 1.1 guidelines.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
-
Adequate hematologic, renal, and hepatic function determined by laboratory blood and urine tests.
-
Availability of recent tumor tissue within 3 months prior to enrollment, when feasible.
Exclusion Criteria:
-
Has known active central nervous system metastases and/or carcinomatous meningitis.
-
History of other malignancy with the past 2 years with some exceptions
-
Evidence of active non-infectious pneumonitis/interstitial lung disease
-
Evidence of other active autoimmune disease that has required prolonged systemic treatment in past 2 years.
-
Evidence of clinically significant immunosuppression such as organ or stem cell transplantation, any severe congenital or acquired cellular and/or humoral immune deficiency, concurrent opportunistic infection.
-
Receiving systemic immunostimulatory agents within 6 weeks or 5 half-lives, whichever is shorter, prior to first dose of study treatment (except ant PD-1/PD-L1 treatment if recruited into Group 4a or 4b).
-
Evidence of active infection within 2 weeks prior to first dose of study treatment.
-
Prior chemotherapy, radiotherapy, biological cancer therapy or major surgery within 28 days prior to enrollment
-
Currently participating or has participated in a study (treatment period only) of an investigational agent or used an investigational device within 28 days of enrollment
-
Received live vaccine within 28 days prior to enrollment
-
Adverse event due to cancer therapy administered more than 28 days prior to enrollment that has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better.
-
Positive for human immunodeficiency virus (HIV), Hepatitis B or C
-
Women planning to become pregnant or who are lactating/breastfeeding while on study through 4 months after receiving the last dose of study drug.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Atlanta | Georgia | United States | 30332 |
| 2 | Research Site | Boston | Massachusetts | United States | 02114 |
| 3 | Research Site | Boston | Massachusetts | United States | 02215 |
| 4 | Research Site | Grand Rapids | Michigan | United States | 49546 |
| 5 | Research Site | New York | New York | United States | 10021 |
| 6 | Research Site | Philadelphia | Pennsylvania | United States | 19111 |
| 7 | Research Site | Greenville | South Carolina | United States | 29605 |
| 8 | South Texas Accelerated Research Therapeutics | San Antonio | Texas | United States | 78229 |
| 9 | Research Site | Camperdown | New South Wales | Australia | 2050 |
| 10 | Research Site | Parkville | Victoria | Australia | 3050 |
| 11 | Research Site | Wilrijk | Belgium | 2610 | |
| 12 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G 2M9 |
| 13 | Research Site | Heidelberg | Germany | 69120 | |
| 14 | Research Site | Madrid | Spain | 28040 | |
| 15 | Research Site | Madrid | Spain | 28050 |
Sponsors and Collaborators
- Amgen
- Merck Sharp & Dohme LLC
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT02713529
Other Study ID Numbers:
- 20150195
- MASTERKEY
- 2016-001080-36
- KEYNOTE-347
First Posted:
Mar 18, 2016
Last Update Posted:
Jul 17, 2020
Last Verified:
Jul 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 15 centers in Australia, Canada, United States of America, and Europe. |
|---|---|
| Pre-assignment Detail | Part 1 was a phase Ib safety study comprised of two cohorts. Part 2 was a phase 2 safety and efficacy study comprised of 5 groups. |
| Arm/Group Title | Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg | Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If >= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Period Title: Overall Study | |||||||
| STARTED | 8 | 7 | 42 | 31 | 4 | 19 | 6 |
| COMPLETED | 1 | 3 | 11 | 2 | 1 | 5 | 2 |
| NOT COMPLETED | 7 | 4 | 31 | 29 | 3 | 14 | 4 |
Baseline Characteristics
| Arm/Group Title | Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg | Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If >= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Total of all reporting groups |
| Overall Participants | 8 | 7 | 42 | 31 | 4 | 19 | 6 | 117 |
| Age, Customized (Count of Participants) | ||||||||
| 18-64 years |
2
25%
|
6
85.7%
|
24
57.1%
|
18
58.1%
|
3
75%
|
7
36.8%
|
4
66.7%
|
64
54.7%
|
| 65-74 years |
6
75%
|
1
14.3%
|
15
35.7%
|
10
32.3%
|
1
25%
|
6
31.6%
|
2
33.3%
|
41
35%
|
| 75-84 years |
0
0%
|
0
0%
|
3
7.1%
|
3
9.7%
|
0
0%
|
5
26.3%
|
0
0%
|
11
9.4%
|
| >=85 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.3%
|
0
0%
|
1
0.9%
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
5
62.5%
|
3
42.9%
|
16
38.1%
|
14
45.2%
|
1
25%
|
1
5.3%
|
3
50%
|
43
36.8%
|
| Male |
3
37.5%
|
4
57.1%
|
26
61.9%
|
17
54.8%
|
3
75%
|
18
94.7%
|
3
50%
|
74
63.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||
| Hispanic or Latino |
0
0%
|
1
14.3%
|
3
7.1%
|
1
3.2%
|
0
0%
|
0
0%
|
0
0%
|
5
4.3%
|
| Not Hispanic or Latino |
8
100%
|
6
85.7%
|
36
85.7%
|
29
93.5%
|
4
100%
|
19
100%
|
6
100%
|
108
92.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
3
7.1%
|
1
3.2%
|
0
0%
|
0
0%
|
0
0%
|
4
3.4%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
14.3%
|
1
2.4%
|
3
9.7%
|
0
0%
|
0
0%
|
0
0%
|
5
4.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
0
0%
|
2
10.5%
|
1
16.7%
|
4
3.4%
|
| White |
8
100%
|
5
71.4%
|
39
92.9%
|
26
83.9%
|
4
100%
|
17
89.5%
|
5
83.3%
|
104
88.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
14.3%
|
2
4.8%
|
1
3.2%
|
0
0%
|
0
0%
|
0
0%
|
4
3.4%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants) | ||||||||
| Grade 0 |
6
75%
|
4
57.1%
|
19
45.2%
|
7
22.6%
|
1
25%
|
4
21.1%
|
2
33.3%
|
43
36.8%
|
| Grade 1 |
2
25%
|
3
42.9%
|
23
54.8%
|
24
77.4%
|
3
75%
|
15
78.9%
|
4
66.7%
|
74
63.2%
|
| Grade 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Grade 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Number of Prior Line of Therapy (Count of Participants) | ||||||||
| 0 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 1 |
0
0%
|
0
0%
|
2
4.8%
|
3
9.7%
|
3
75%
|
1
5.3%
|
0
0%
|
9
7.7%
|
| 2 |
1
12.5%
|
1
14.3%
|
9
21.4%
|
13
41.9%
|
1
25%
|
7
36.8%
|
3
50%
|
35
29.9%
|
| 3 |
4
50%
|
3
42.9%
|
11
26.2%
|
8
25.8%
|
0
0%
|
7
36.8%
|
3
50%
|
36
30.8%
|
| 4 |
1
12.5%
|
1
14.3%
|
10
23.8%
|
5
16.1%
|
0
0%
|
1
5.3%
|
0
0%
|
18
15.4%
|
| 5 |
2
25%
|
2
28.6%
|
10
23.8%
|
2
6.5%
|
0
0%
|
3
15.8%
|
0
0%
|
19
16.2%
|
| >5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Disease Stage at Screening (Count of Participants) | ||||||||
| Stage I |
1
12.5%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
1.7%
|
| Stage II |
1
12.5%
|
0
0%
|
3
7.1%
|
3
9.7%
|
1
25%
|
1
5.3%
|
0
0%
|
9
7.7%
|
| Stage III |
0
0%
|
0
0%
|
4
9.5%
|
2
6.5%
|
0
0%
|
2
10.5%
|
1
16.7%
|
9
7.7%
|
| Stage IV |
6
75%
|
6
85.7%
|
35
83.3%
|
26
83.9%
|
3
75%
|
16
84.2%
|
5
83.3%
|
97
82.9%
|
Outcome Measures
| Title | Participants With Dose Limiting Toxicities (DLT) |
|---|---|
| Description | DLTs were evaluated by the Dose Level Review Team (DLRT). A DLT was defined as any grade >=3 adverse event occurring during a DLT time window (21 day period from the initial administration of AMG 820 and pembrolizumab in combination), and if judged by the investigator to be related to the administration of AMG 820 and/or pembrolizumab. |
| Time Frame | The DLT evaluation period was Day 1 to Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg | Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If >= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 8 | 7 | 41 | 31 | 4 | 19 | 6 |
| Participants with treatment emergent DLTs |
0
0%
|
1
14.3%
|
3
7.1%
|
2
6.5%
|
0
0%
|
1
5.3%
|
0
0%
|
| DLT: Autoimmune pancreatitis |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| DLT: Autoimmune hepatitis |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| DLT: Cholecystitis |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| DLT: Electrolyte imbalance |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| DLT: Fatigue |
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| DLT: Aspartate aminotransferase increased |
0
0%
|
0
0%
|
1
2.4%
|
1
3.2%
|
0
0%
|
0
0%
|
0
0%
|
| DLT: Lipase increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.3%
|
0
0%
|
| DLT: Epilepsy |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
0
0%
|
0
0%
|
0
0%
|
| DLT: Rash generalised |
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| DLT: Rash maculo-papular |
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Participants With Treatment -Emergent Adverse Events (TEAEs) |
|---|---|
| Description | TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe. |
| Time Frame | Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg | Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If >= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 8 | 7 | 41 | 31 | 4 | 19 | 6 |
| >=1 TEAE |
8
100%
|
7
100%
|
41
97.6%
|
31
100%
|
4
100%
|
19
100%
|
6
100%
|
| Grade >=3 |
7
87.5%
|
7
100%
|
40
95.2%
|
30
96.8%
|
4
100%
|
19
100%
|
6
100%
|
| Grade >=4 |
2
25%
|
4
57.1%
|
24
57.1%
|
26
83.9%
|
2
50%
|
12
63.2%
|
4
66.7%
|
| Grade >=5 |
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
| Serious AE |
5
62.5%
|
2
28.6%
|
31
73.8%
|
23
74.2%
|
3
75%
|
11
57.9%
|
5
83.3%
|
| Leading to interruption of AMG 820 |
4
50%
|
3
42.9%
|
23
54.8%
|
7
22.6%
|
1
25%
|
7
36.8%
|
2
33.3%
|
| Leading to discontinuation AMG 820 |
0
0%
|
0
0%
|
6
14.3%
|
5
16.1%
|
2
50%
|
1
5.3%
|
3
50%
|
| ---- SAE leading to d/c AMG 820 |
0
0%
|
0
0%
|
4
9.5%
|
4
12.9%
|
1
25%
|
0
0%
|
2
33.3%
|
| ----Non-serious AE leading to d/c AMG 820 |
0
0%
|
0
0%
|
2
4.8%
|
1
3.2%
|
1
25%
|
1
5.3%
|
1
16.7%
|
| Leading to discontinuation of PEM |
1
12.5%
|
0
0%
|
7
16.7%
|
5
16.1%
|
2
50%
|
1
5.3%
|
3
50%
|
| ---- SAE leading to d/c PEM |
0
0%
|
0
0%
|
4
9.5%
|
4
12.9%
|
1
25%
|
0
0%
|
2
33.3%
|
| ----Non-serious AE leading to d/c PEM |
1
12.5%
|
0
0%
|
3
7.1%
|
1
3.2%
|
1
25%
|
1
5.3%
|
1
16.7%
|
| Fatal TEAE |
1
12.5%
|
0
0%
|
4
9.5%
|
3
9.7%
|
0
0%
|
3
15.8%
|
2
33.3%
|
| TEAE related to study procedure/activity |
0
0%
|
1
14.3%
|
11
26.2%
|
5
16.1%
|
0
0%
|
3
15.8%
|
1
16.7%
|
| Title | Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment |
|---|---|
| Description | TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe. |
| Time Frame | Day 1 up to 207 days for Part 1; Day 1 up to 572 days for Part 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg | Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If >= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 8 | 7 | 41 | 31 | 4 | 19 | 6 |
| >=1 TEAE |
5
62.5%
|
7
100%
|
41
97.6%
|
25
80.6%
|
4
100%
|
14
73.7%
|
6
100%
|
| Grade >=3 |
3
37.5%
|
5
71.4%
|
28
66.7%
|
11
35.5%
|
1
25%
|
10
52.6%
|
6
100%
|
| Grade >=4 |
1
12.5%
|
1
14.3%
|
5
11.9%
|
5
16.1%
|
0
0%
|
2
10.5%
|
2
33.3%
|
| Grade >=5 |
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
| Serious AE |
2
25%
|
2
28.6%
|
12
28.6%
|
4
12.9%
|
0
0%
|
3
15.8%
|
3
50%
|
| Leading to interruption of AMG 820 |
2
25%
|
3
42.9%
|
16
38.1%
|
7
22.6%
|
0
0%
|
5
26.3%
|
2
33.3%
|
| Leading to discontinuation AMG 820 |
0
0%
|
0
0%
|
3
7.1%
|
3
9.7%
|
1
25%
|
0
0%
|
3
50%
|
| ---- SAE leading to d/c AMG 820 |
0
0%
|
0
0%
|
3
7.1%
|
2
6.5%
|
0
0%
|
0
0%
|
2
33.3%
|
| ----Non-serious AE leading to d/c AMG 820 |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
1
25%
|
0
0%
|
1
16.7%
|
| Leading to discontinuation of PEM |
0
0%
|
0
0%
|
4
9.5%
|
3
9.7%
|
1
25%
|
0
0%
|
3
50%
|
| ---- SAE leading to d/c PEM |
0
0%
|
0
0%
|
3
7.1%
|
2
6.5%
|
0
0%
|
0
0%
|
2
33.3%
|
| ----Non-serious AE leading to d/c PEM |
0
0%
|
0
0%
|
1
2.4%
|
1
3.2%
|
1
25%
|
0
0%
|
1
16.7%
|
| Fatal TEAE |
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| TEAE related to study procedure/activity |
0
0%
|
0
0%
|
8
19%
|
2
6.5%
|
0
0%
|
3
15.8%
|
1
16.7%
|
| Title | Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment |
|---|---|
| Description | TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe. |
| Time Frame | Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg | Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If >= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 8 | 7 | 41 | 31 | 4 | 19 | 6 |
| >=1 TEAE |
5
62.5%
|
7
100%
|
39
92.9%
|
24
77.4%
|
4
100%
|
13
68.4%
|
6
100%
|
| Grade >=3 |
2
25%
|
5
71.4%
|
29
69%
|
9
29%
|
1
25%
|
10
52.6%
|
4
66.7%
|
| Grade >=4 |
1
12.5%
|
1
14.3%
|
5
11.9%
|
4
12.9%
|
0
0%
|
2
10.5%
|
2
33.3%
|
| Grade >=5 |
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
| Serious AE |
2
25%
|
2
28.6%
|
16
38.1%
|
5
16.1%
|
0
0%
|
3
15.8%
|
4
66.7%
|
| Leading to interruption of PEM |
1
12.5%
|
3
42.9%
|
15
35.7%
|
6
19.4%
|
0
0%
|
5
26.3%
|
2
33.3%
|
| Leading to discontinuation AMG 820 |
0
0%
|
0
0%
|
4
9.5%
|
2
6.5%
|
1
25%
|
1
5.3%
|
3
50%
|
| ---- SAE leading to d/c AMG 820 |
0
0%
|
0
0%
|
3
7.1%
|
1
3.2%
|
0
0%
|
0
0%
|
2
33.3%
|
| ----Non-serious AE leading to d/c AMG 820 |
0
0%
|
0
0%
|
1
2.4%
|
1
3.2%
|
1
25%
|
1
5.3%
|
1
16.7%
|
| Leading to discontinuation of PEM |
0
0%
|
0
0%
|
5
11.9%
|
2
6.5%
|
1
25%
|
1
5.3%
|
3
50%
|
| ---- SAE leading to d/c PEM |
0
0%
|
0
0%
|
3
7.1%
|
1
3.2%
|
0
0%
|
0
0%
|
2
33.3%
|
| ----Non-serious AE leading to d/c PEM |
0
0%
|
0
0%
|
2
4.8%
|
1
3.2%
|
1
25%
|
1
5.3%
|
1
16.7%
|
| Fatal TEAE |
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
| TEAE related to study procedure/activity |
0
0%
|
0
0%
|
9
21.4%
|
3
9.7%
|
0
0%
|
2
10.5%
|
1
16.7%
|
| Title | Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) |
|---|---|
| Description | ORR was defined as the percentage of participants with a best overall response of complete response or partial response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). During treatment radiographic imaging was performed at Week 10 and repeated at least every 10 weeks until disease progression. Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required. |
| Time Frame | Baseline: Day -28; Treatment: up to Month 13.7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1: AMG 820 + Pem | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohorts 1 + 2 combined. Participants with advanced solid tumors were treated with 1400 mg or 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 15 | 41 | 31 | 4 | 19 | 6 |
| Number (95% Confidence Interval) [percentage of participants] |
0.0
0%
|
4.9
70%
|
0.0
0%
|
0.0
0%
|
5.3
132.5%
|
0.0
0%
|
| Title | Time to Response (TTR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) For Participants Who Responded |
|---|---|
| Description | Time to response was defined as the time from first dose of AMG 820 until first documented complete or partial response per irRECIST divided by 365.25 days/12. |
| Time Frame | Day 1 up to Month 16 (max time to censoring) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1: AMG 820 + Pem | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohorts 1 + 2 combined. Participants with advanced solid tumors were treated with 1400 mg or 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 0 | 2 | 0 | 0 | 1 | 0 |
| Mean (Full Range) [month] |
2.1587
|
2.0698
|
| Title | Time to Progression (TTP) for Participants Who Had Progressive Disease |
|---|---|
| Description | Time to progression was defined as the time from first dose of AMG 820 until first documented progressive disease per irRECIST divided by 365.25 days/12. |
| Time Frame | Day 1 up to 14.4 months (max time to censoring) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1: AMG 820 + Pem | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohorts 1 + 2 combined. Participants with advanced solid tumors were treated with 1400 mg or 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 10 | 29 | 13 | 3 | 8 | 4 |
| Mean (Full Range) [month] |
2.1865
|
3.0691
|
2.3878
|
4.6762
|
6.0863
|
7.7864
|
| Title | Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12 |
|---|---|
| Description | Overall survival time was calculated as the number of days from the first administration of AMG 820 to date of death or censoring divided by (365.25/12). Data are reported as the percentage of participants who were alive at Month 6 and Month 12. |
| Time Frame | Day 1 up to Month 6 or Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1: AMG 820 + Pem 200 mg | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohorts 1 + 2 combined. Participants with advanced solid tumors were treated with 1400 mg or 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 15 | 41 | 31 | 4 | 19 | 6 |
| Month 6 |
59.077
738.5%
|
53.915
770.2%
|
16.705
39.8%
|
75.000
241.9%
|
52.105
1302.6%
|
41.667
219.3%
|
| Month 12 |
47.262
590.8%
|
38.963
556.6%
|
8.353
19.9%
|
25.00
80.6%
|
34.737
868.4%
|
41.667
219.3%
|
| Title | Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and Month 12 |
|---|---|
| Description | Progression-free survival time was calculated as the number of days from the first administration of AMG 820 to date of progressive disease or death or censoring divided by (365.25/12). Data are reported as the percentage of participants who were alive and progression-free at Month 6 and Month 12. |
| Time Frame | Day 1 up to Month 6 or Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part 1: AMG 820 + Pem 200 mg | Part 2, Group 1: CRC MMR-proficient | Part 2, Group 2: Pancreatic Cancer | Part 2, Group 3: NSCLC PD-L1 Low, Naïve | Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low | Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High |
|---|---|---|---|---|---|---|
| Arm/Group Description | Part 1 Cohorts 1 + 2 combined. Participants with advanced solid tumors were treated with 1400 mg or 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. | Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. | Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent. |
| Measure Participants | 15 | 41 | 31 | 4 | 19 | 6 |
| Month 6 |
10.476
131%
|
13.490
192.7%
|
0.000
0%
|
25.000
80.6%
|
26.471
661.8%
|
33.333
175.4%
|
| Month 12 |
0.000
0%
|
5.396
77.1%
|
0.000
0%
|
0.000
0%
|
6.618
165.5%
|
33.333
175.4%
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2 |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Cycle 1 |
2.0
|
2.0
|
| Cycle 2 |
3.00
|
2.00
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Maximum Observed Drug Concentration (Cmax) During Treatment Cycles 1 + 2 |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Cycle 1 |
331
(27)
|
485
(23)
|
| Cycle 2 |
363
(32)
|
536
(21)
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Last (AUClast) During Treatment Cycles 1 + 2 |
|---|---|
| Description | AUClast is the area under the serum concentration-time curve from time zero to time of last quantifiable concentration. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Cycle 1 |
55100
(37)
|
80400
(33)
|
| Cycle 2 |
55200
(38)
|
73500
(45)
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Over the Dose Interval (AUCtau) During Treatment Cycles 1 + 2 |
|---|---|
| Description | AUCtau is the area under the serum concentration-time curve over the dose interval tau, with tau equal to 21 days. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Cycle 1 |
59300
(33)
|
90000
(29)
|
| Cycle 2 |
75400
(35)
|
114000
(31)
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Minimum Observed Drug Concentration (Cmin) During Treatment Cycles 1 + 2 |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Cycle 1 |
49.9
(51)
|
90.9
(35)
|
| Cycle 2 |
78.7
(66)
|
199
(34)
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Terminal Elimination Half-life (t1/2z) During Treatment Cycles 1 + 2 |
|---|---|
| Description | |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Cycle 1 |
217
(26)
|
214
(24)
|
| Cycle 2 |
170
(16)
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Volume of Distribution (Vz) During Treatment Cycles 1 + 2 |
|---|---|
| Description | Volume of distribution observed at terminal phase after intravenous dosing. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Cycle 1 |
5200
(35)
|
4110
(25)
|
| Cycle 2 |
4560
(21)
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Drug Clearance (CL) During Treatment Cycles 1 + 2 |
|---|---|
| Description | Drug clearance observed after intravenous dosing. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Cycle 1 |
16.6
(37)
|
13.3
(33)
|
| Cycle 2 |
18.6
(30)
|
| Title | AMG 820 Pharmacokinetic Parameter by Dose Group: Accumulation Ratio (AR) |
|---|---|
| Description | Accumulation ratio is AUCtau following administration in Cycle 2 / AUCtau after administration in Cycle 1 |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected. |
| Arm/Group Title | AMG 820 1100 mg | AMG 820 1400 mg |
|---|---|---|
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms who were administered AMG 820 1400 mg |
| Measure Participants | 97 | 18 |
| Geometric Mean (Geometric Coefficient of Variation) [ratio] |
1.23
(18)
|
1.25
(16)
|
Adverse Events
| Time Frame | The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries. | |||
| Arm/Group Title | AMG 820 1100 MG | AMG 820 1400 MG | ||
| Arm/Group Description | Includes participants from all treatment arms that were administered AMG 820 1100 mg. | Includes participants from all treatment arms that were administered AMG 820 1400 mg. | ||
All Cause Mortality |
||||
| AMG 820 1100 MG | AMG 820 1400 MG | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/98 (12.2%) | 1/18 (5.6%) | ||
Serious Adverse Events |
||||
| AMG 820 1100 MG | AMG 820 1400 MG | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 70/98 (71.4%) | 10/18 (55.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/98 (3.1%) | 0/18 (0%) | ||
| Febrile neutropenia | 1/98 (1%) | 0/18 (0%) | ||
| Cardiac disorders | ||||
| Atrial flutter | 1/98 (1%) | 0/18 (0%) | ||
| Cardiac arrest | 1/98 (1%) | 0/18 (0%) | ||
| Cardiac failure congestive | 1/98 (1%) | 0/18 (0%) | ||
| Pericardial effusion | 1/98 (1%) | 0/18 (0%) | ||
| Eye disorders | ||||
| Periorbital oedema | 0/98 (0%) | 1/18 (5.6%) | ||
| Uveitis | 0/98 (0%) | 1/18 (5.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 3/98 (3.1%) | 2/18 (11.1%) | ||
| Abdominal pain upper | 2/98 (2%) | 0/18 (0%) | ||
| Autoimmune pancreatitis | 0/98 (0%) | 1/18 (5.6%) | ||
| Colitis | 1/98 (1%) | 0/18 (0%) | ||
| Diarrhoea | 1/98 (1%) | 0/18 (0%) | ||
| Duodenal perforation | 1/98 (1%) | 0/18 (0%) | ||
| Enterovesical fistula | 1/98 (1%) | 0/18 (0%) | ||
| Gastrointestinal haemorrhage | 1/98 (1%) | 0/18 (0%) | ||
| Ileus | 1/98 (1%) | 0/18 (0%) | ||
| Nausea | 1/98 (1%) | 1/18 (5.6%) | ||
| Obstruction gastric | 0/98 (0%) | 1/18 (5.6%) | ||
| Proctalgia | 1/98 (1%) | 0/18 (0%) | ||
| Small intestinal obstruction | 1/98 (1%) | 0/18 (0%) | ||
| Upper gastrointestinal haemorrhage | 1/98 (1%) | 1/18 (5.6%) | ||
| Vomiting | 1/98 (1%) | 1/18 (5.6%) | ||
| General disorders | ||||
| Asthenia | 3/98 (3.1%) | 0/18 (0%) | ||
| Fatigue | 2/98 (2%) | 2/18 (11.1%) | ||
| Malaise | 1/98 (1%) | 0/18 (0%) | ||
| Non-cardiac chest pain | 1/98 (1%) | 0/18 (0%) | ||
| Oedema peripheral | 1/98 (1%) | 0/18 (0%) | ||
| Pyrexia | 8/98 (8.2%) | 0/18 (0%) | ||
| Hepatobiliary disorders | ||||
| Autoimmune hepatitis | 0/98 (0%) | 1/18 (5.6%) | ||
| Bile duct obstruction | 3/98 (3.1%) | 0/18 (0%) | ||
| Biliary colic | 1/98 (1%) | 0/18 (0%) | ||
| Cholecystitis | 0/98 (0%) | 1/18 (5.6%) | ||
| Hepatitis | 2/98 (2%) | 0/18 (0%) | ||
| Hepatotoxicity | 0/98 (0%) | 1/18 (5.6%) | ||
| Immune-mediated hepatitis | 1/98 (1%) | 0/18 (0%) | ||
| Infections and infestations | ||||
| Abdominal infection | 1/98 (1%) | 0/18 (0%) | ||
| Bacteraemia | 0/98 (0%) | 1/18 (5.6%) | ||
| Cellulitis | 2/98 (2%) | 0/18 (0%) | ||
| Clostridium difficile infection | 1/98 (1%) | 0/18 (0%) | ||
| Cystitis | 0/98 (0%) | 1/18 (5.6%) | ||
| Device related infection | 3/98 (3.1%) | 0/18 (0%) | ||
| Endocarditis staphylococcal | 1/98 (1%) | 0/18 (0%) | ||
| Influenza | 1/98 (1%) | 0/18 (0%) | ||
| Klebsiella bacteraemia | 1/98 (1%) | 0/18 (0%) | ||
| Liver abscess | 1/98 (1%) | 0/18 (0%) | ||
| Lower respiratory tract infection | 1/98 (1%) | 0/18 (0%) | ||
| Lung infection | 2/98 (2%) | 0/18 (0%) | ||
| Pelvic abscess | 1/98 (1%) | 0/18 (0%) | ||
| Pneumonia | 3/98 (3.1%) | 2/18 (11.1%) | ||
| Pneumonia bacterial | 1/98 (1%) | 0/18 (0%) | ||
| Sepsis | 1/98 (1%) | 0/18 (0%) | ||
| Septic shock | 1/98 (1%) | 0/18 (0%) | ||
| Staphylococcal sepsis | 1/98 (1%) | 0/18 (0%) | ||
| Urinary tract infection | 5/98 (5.1%) | 0/18 (0%) | ||
| Urosepsis | 1/98 (1%) | 0/18 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/98 (1%) | 0/18 (0%) | ||
| Aspartate aminotransferase increased | 3/98 (3.1%) | 0/18 (0%) | ||
| Blood alkaline phosphatase increased | 1/98 (1%) | 0/18 (0%) | ||
| Hepatic enzyme increased | 1/98 (1%) | 1/18 (5.6%) | ||
| Transaminases increased | 2/98 (2%) | 0/18 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Diabetes mellitus | 1/98 (1%) | 0/18 (0%) | ||
| Electrolyte imbalance | 0/98 (0%) | 1/18 (5.6%) | ||
| Failure to thrive | 1/98 (1%) | 0/18 (0%) | ||
| Hypercalcaemia | 2/98 (2%) | 0/18 (0%) | ||
| Hyperkalaemia | 2/98 (2%) | 0/18 (0%) | ||
| Hypoalbuminaemia | 1/98 (1%) | 0/18 (0%) | ||
| Hypokalaemia | 1/98 (1%) | 0/18 (0%) | ||
| Hyponatraemia | 1/98 (1%) | 0/18 (0%) | ||
| Hypophosphataemia | 1/98 (1%) | 0/18 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/98 (1%) | 1/18 (5.6%) | ||
| Musculoskeletal chest pain | 1/98 (1%) | 0/18 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 0/98 (0%) | 1/18 (5.6%) | ||
| Colorectal cancer | 2/98 (2%) | 0/18 (0%) | ||
| Colorectal cancer metastatic | 1/98 (1%) | 0/18 (0%) | ||
| Malignant pleural effusion | 1/98 (1%) | 0/18 (0%) | ||
| Non-small cell lung cancer | 1/98 (1%) | 0/18 (0%) | ||
| Non-small cell lung cancer metastatic | 2/98 (2%) | 0/18 (0%) | ||
| Pancreatic carcinoma metastatic | 1/98 (1%) | 0/18 (0%) | ||
| Rectal cancer | 1/98 (1%) | 0/18 (0%) | ||
| Tumour flare | 1/98 (1%) | 0/18 (0%) | ||
| Tumour haemorrhage | 1/98 (1%) | 1/18 (5.6%) | ||
| Nervous system disorders | ||||
| Cerebellar infarction | 1/98 (1%) | 0/18 (0%) | ||
| Cerebrovascular accident | 2/98 (2%) | 0/18 (0%) | ||
| Dizziness | 1/98 (1%) | 0/18 (0%) | ||
| Embolic cerebral infarction | 1/98 (1%) | 0/18 (0%) | ||
| Encephalopathy | 1/98 (1%) | 0/18 (0%) | ||
| Epilepsy | 1/98 (1%) | 0/18 (0%) | ||
| Product Issues | ||||
| Device dislocation | 1/98 (1%) | 0/18 (0%) | ||
| Psychiatric disorders | ||||
| Mental status changes | 0/98 (0%) | 1/18 (5.6%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 2/98 (2%) | 0/18 (0%) | ||
| Haematuria | 2/98 (2%) | 0/18 (0%) | ||
| Nephritis | 1/98 (1%) | 0/18 (0%) | ||
| Nephrotic syndrome | 0/98 (0%) | 1/18 (5.6%) | ||
| Renal haemorrhage | 1/98 (1%) | 0/18 (0%) | ||
| Urinary tract obstruction | 1/98 (1%) | 0/18 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 3/98 (3.1%) | 0/18 (0%) | ||
| Hypoxia | 1/98 (1%) | 0/18 (0%) | ||
| Pharyngeal inflammation | 1/98 (1%) | 0/18 (0%) | ||
| Pleural effusion | 4/98 (4.1%) | 0/18 (0%) | ||
| Pneumonitis | 3/98 (3.1%) | 1/18 (5.6%) | ||
| Pulmonary embolism | 2/98 (2%) | 0/18 (0%) | ||
| Respiratory failure | 1/98 (1%) | 0/18 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Erythema nodosum | 1/98 (1%) | 0/18 (0%) | ||
| Rash | 1/98 (1%) | 0/18 (0%) | ||
| Rash generalised | 1/98 (1%) | 0/18 (0%) | ||
| Rash maculo-papular | 3/98 (3.1%) | 0/18 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| AMG 820 1100 MG | AMG 820 1400 MG | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 97/98 (99%) | 18/18 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 35/98 (35.7%) | 4/18 (22.2%) | ||
| Cardiac disorders | ||||
| Bradycardia | 1/98 (1%) | 1/18 (5.6%) | ||
| Endocrine disorders | ||||
| Hypothyroidism | 6/98 (6.1%) | 0/18 (0%) | ||
| Parathyroid disorder | 0/98 (0%) | 1/18 (5.6%) | ||
| Eye disorders | ||||
| Periorbital oedema | 38/98 (38.8%) | 10/18 (55.6%) | ||
| Periorbital swelling | 2/98 (2%) | 1/18 (5.6%) | ||
| Photophobia | 0/98 (0%) | 1/18 (5.6%) | ||
| Uveitis | 0/98 (0%) | 1/18 (5.6%) | ||
| Vision blurred | 2/98 (2%) | 2/18 (11.1%) | ||
| Visual impairment | 0/98 (0%) | 1/18 (5.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 6/98 (6.1%) | 1/18 (5.6%) | ||
| Abdominal pain | 20/98 (20.4%) | 6/18 (33.3%) | ||
| Ascites | 6/98 (6.1%) | 0/18 (0%) | ||
| Constipation | 22/98 (22.4%) | 9/18 (50%) | ||
| Diarrhoea | 23/98 (23.5%) | 5/18 (27.8%) | ||
| Dry mouth | 8/98 (8.2%) | 3/18 (16.7%) | ||
| Duodenal obstruction | 0/98 (0%) | 1/18 (5.6%) | ||
| Dyspepsia | 5/98 (5.1%) | 0/18 (0%) | ||
| Dysphagia | 3/98 (3.1%) | 1/18 (5.6%) | ||
| Flatulence | 2/98 (2%) | 1/18 (5.6%) | ||
| Gastrooesophageal reflux disease | 2/98 (2%) | 1/18 (5.6%) | ||
| Nausea | 26/98 (26.5%) | 7/18 (38.9%) | ||
| Oral pain | 0/98 (0%) | 1/18 (5.6%) | ||
| Proctalgia | 1/98 (1%) | 1/18 (5.6%) | ||
| Rectal haemorrhage | 2/98 (2%) | 1/18 (5.6%) | ||
| Stomatitis | 3/98 (3.1%) | 1/18 (5.6%) | ||
| Vomiting | 12/98 (12.2%) | 5/18 (27.8%) | ||
| General disorders | ||||
| Asthenia | 8/98 (8.2%) | 0/18 (0%) | ||
| Chills | 11/98 (11.2%) | 3/18 (16.7%) | ||
| Face oedema | 14/98 (14.3%) | 5/18 (27.8%) | ||
| Fatigue | 52/98 (53.1%) | 10/18 (55.6%) | ||
| Hyperthermia malignant | 0/98 (0%) | 1/18 (5.6%) | ||
| Oedema | 4/98 (4.1%) | 1/18 (5.6%) | ||
| Oedema peripheral | 10/98 (10.2%) | 2/18 (11.1%) | ||
| Pain | 6/98 (6.1%) | 0/18 (0%) | ||
| Pyrexia | 25/98 (25.5%) | 3/18 (16.7%) | ||
| Hepatobiliary disorders | ||||
| Hepatotoxicity | 0/98 (0%) | 1/18 (5.6%) | ||
| Portal vein thrombosis | 0/98 (0%) | 1/18 (5.6%) | ||
| Infections and infestations | ||||
| Bacteraemia | 0/98 (0%) | 1/18 (5.6%) | ||
| Candida infection | 8/98 (8.2%) | 0/18 (0%) | ||
| Conjunctivitis | 1/98 (1%) | 1/18 (5.6%) | ||
| Lower respiratory tract infection | 0/98 (0%) | 1/18 (5.6%) | ||
| Lung infection | 3/98 (3.1%) | 1/18 (5.6%) | ||
| Mucosal infection | 0/98 (0%) | 2/18 (11.1%) | ||
| Oral candidiasis | 5/98 (5.1%) | 0/18 (0%) | ||
| Skin infection | 2/98 (2%) | 1/18 (5.6%) | ||
| Upper respiratory tract infection | 5/98 (5.1%) | 0/18 (0%) | ||
| Urinary tract infection | 6/98 (6.1%) | 0/18 (0%) | ||
| Viral infection | 1/98 (1%) | 1/18 (5.6%) | ||
| Investigations | ||||
| Activated partial thromboplastin time prolonged | 6/98 (6.1%) | 0/18 (0%) | ||
| Alanine aminotransferase | 1/98 (1%) | 1/18 (5.6%) | ||
| Alanine aminotransferase increased | 21/98 (21.4%) | 4/18 (22.2%) | ||
| Amylase increased | 19/98 (19.4%) | 5/18 (27.8%) | ||
| Aspartate aminotransferase abnormal | 0/98 (0%) | 1/18 (5.6%) | ||
| Aspartate aminotransferase increased | 58/98 (59.2%) | 12/18 (66.7%) | ||
| Blood alkaline phosphatase increased | 13/98 (13.3%) | 5/18 (27.8%) | ||
| Blood bilirubin increased | 5/98 (5.1%) | 0/18 (0%) | ||
| Blood creatine phosphokinase increased | 1/98 (1%) | 2/18 (11.1%) | ||
| Blood lactate dehydrogenase increased | 0/98 (0%) | 1/18 (5.6%) | ||
| International normalised ratio increased | 5/98 (5.1%) | 0/18 (0%) | ||
| Lipase increased | 18/98 (18.4%) | 5/18 (27.8%) | ||
| Liver function test abnormal | 0/98 (0%) | 1/18 (5.6%) | ||
| Lymphocyte count decreased | 1/98 (1%) | 1/18 (5.6%) | ||
| Transaminases increased | 7/98 (7.1%) | 0/18 (0%) | ||
| Troponin increased | 0/98 (0%) | 1/18 (5.6%) | ||
| Weight decreased | 6/98 (6.1%) | 1/18 (5.6%) | ||
| White blood cell count decreased | 1/98 (1%) | 1/18 (5.6%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 22/98 (22.4%) | 9/18 (50%) | ||
| Dehydration | 6/98 (6.1%) | 1/18 (5.6%) | ||
| Hyperglycaemia | 4/98 (4.1%) | 1/18 (5.6%) | ||
| Hyperlipasaemia | 5/98 (5.1%) | 0/18 (0%) | ||
| Hyperuricaemia | 1/98 (1%) | 1/18 (5.6%) | ||
| Hypoalbuminaemia | 11/98 (11.2%) | 2/18 (11.1%) | ||
| Hypocalcaemia | 6/98 (6.1%) | 1/18 (5.6%) | ||
| Hypokalaemia | 9/98 (9.2%) | 3/18 (16.7%) | ||
| Hypomagnesaemia | 10/98 (10.2%) | 0/18 (0%) | ||
| Hyponatraemia | 12/98 (12.2%) | 2/18 (11.1%) | ||
| Hypophosphataemia | 18/98 (18.4%) | 8/18 (44.4%) | ||
| Ketoacidosis | 0/98 (0%) | 1/18 (5.6%) | ||
| Vitamin D deficiency | 0/98 (0%) | 1/18 (5.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 9/98 (9.2%) | 2/18 (11.1%) | ||
| Back pain | 10/98 (10.2%) | 1/18 (5.6%) | ||
| Muscular weakness | 5/98 (5.1%) | 0/18 (0%) | ||
| Musculoskeletal pain | 7/98 (7.1%) | 0/18 (0%) | ||
| Myalgia | 2/98 (2%) | 2/18 (11.1%) | ||
| Myopathy | 0/98 (0%) | 1/18 (5.6%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Colon cancer metastatic | 1/98 (1%) | 3/18 (16.7%) | ||
| Colorectal cancer metastatic | 4/98 (4.1%) | 1/18 (5.6%) | ||
| Non-small cell lung cancer metastatic | 2/98 (2%) | 1/18 (5.6%) | ||
| Pancreatic carcinoma | 6/98 (6.1%) | 2/18 (11.1%) | ||
| Pancreatic carcinoma metastatic | 9/98 (9.2%) | 4/18 (22.2%) | ||
| Rectal cancer | 1/98 (1%) | 1/18 (5.6%) | ||
| Tumour haemorrhage | 0/98 (0%) | 1/18 (5.6%) | ||
| Nervous system disorders | ||||
| Akathisia | 0/98 (0%) | 1/18 (5.6%) | ||
| Aphasia | 1/98 (1%) | 1/18 (5.6%) | ||
| Dizziness | 6/98 (6.1%) | 1/18 (5.6%) | ||
| Dysgeusia | 5/98 (5.1%) | 0/18 (0%) | ||
| Facial paresis | 0/98 (0%) | 1/18 (5.6%) | ||
| Headache | 11/98 (11.2%) | 2/18 (11.1%) | ||
| Lethargy | 1/98 (1%) | 1/18 (5.6%) | ||
| Peripheral sensory neuropathy | 0/98 (0%) | 1/18 (5.6%) | ||
| Psychiatric disorders | ||||
| Anxiety | 5/98 (5.1%) | 2/18 (11.1%) | ||
| Confusional state | 6/98 (6.1%) | 1/18 (5.6%) | ||
| Insomnia | 4/98 (4.1%) | 4/18 (22.2%) | ||
| Renal and urinary disorders | ||||
| Bladder spasm | 0/98 (0%) | 1/18 (5.6%) | ||
| Haematuria | 7/98 (7.1%) | 1/18 (5.6%) | ||
| Nephrotic syndrome | 0/98 (0%) | 1/18 (5.6%) | ||
| Proteinuria | 1/98 (1%) | 1/18 (5.6%) | ||
| Urinary retention | 0/98 (0%) | 1/18 (5.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 19/98 (19.4%) | 1/18 (5.6%) | ||
| Dyspnoea | 22/98 (22.4%) | 3/18 (16.7%) | ||
| Hiccups | 2/98 (2%) | 1/18 (5.6%) | ||
| Nasal congestion | 5/98 (5.1%) | 1/18 (5.6%) | ||
| Oropharyngeal pain | 3/98 (3.1%) | 1/18 (5.6%) | ||
| Pleural effusion | 9/98 (9.2%) | 0/18 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dry skin | 5/98 (5.1%) | 0/18 (0%) | ||
| Photosensitivity reaction | 0/98 (0%) | 1/18 (5.6%) | ||
| Pruritus | 19/98 (19.4%) | 4/18 (22.2%) | ||
| Rash | 25/98 (25.5%) | 2/18 (11.1%) | ||
| Rash maculo-papular | 14/98 (14.3%) | 5/18 (27.8%) | ||
| Skin lesion | 0/98 (0%) | 1/18 (5.6%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 2/98 (2%) | 1/18 (5.6%) | ||
| Embolism | 2/98 (2%) | 1/18 (5.6%) | ||
| Hypertension | 16/98 (16.3%) | 4/18 (22.2%) | ||
| Hypotension | 5/98 (5.1%) | 0/18 (0%) | ||
| Venous thrombosis | 1/98 (1%) | 1/18 (5.6%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
| medinfo@amgen.com |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT02713529
Other Study ID Numbers:
- 20150195
- MASTERKEY
- 2016-001080-36
- KEYNOTE-347
First Posted:
Mar 18, 2016
Last Update Posted:
Jul 17, 2020
Last Verified:
Jul 1, 2020