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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02713529




Registration number
NCT02713529
Ethics application status
Date submitted
3/03/2016
Date registered
18/03/2016
Date last updated
1/06/2020

Titles & IDs
Public title
Safety and Efficacy Study of AMG 820 and Pembrolizumab Combination in Select Advanced Solid Tumor Cancer
Scientific title
A Phase1b/2 Study Assessing Safety and Anti-tumor Activity of AMG 820 in Combination With Pembrolizumab in Select Advanced Solid Tumors
Secondary ID [1] 0 0
MASTERKEY
Secondary ID [2] 0 0
20150195
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 0 0
Colorectal Cancer 0 0
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AMG820 and pembrolizumab

Experimental: AMG820 and pembrolizumab - Treatment with AMG820 and pembrolizumab


Other interventions: AMG820 and pembrolizumab
Treatment with AMG820 and pembrolizumab

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Participants With Dose Limiting Toxicities (DLT) - 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.
Timepoint [1] 0 0
The DLT evaluation period was Day 1 to Day 21
Primary outcome [2] 0 0
Participants With Treatment -Emergent Adverse Events (TEAEs) - 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.
Timepoint [2] 0 0
Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2
Primary outcome [3] 0 0
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment - 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.
Timepoint [3] 0 0
Day 1 up to 207 days for Part 1; Day 1 up to 572 days for Part 2
Primary outcome [4] 0 0
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment - 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.
Timepoint [4] 0 0
Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2
Primary outcome [5] 0 0
Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) - 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.
Timepoint [5] 0 0
Baseline: Day -28; Treatment: up to Month 13.7
Secondary outcome [1] 0 0
Time to Response (TTR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) For Participants Who Responded - 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.
Timepoint [1] 0 0
Day 1 up to Month 16 (max time to censoring)
Secondary outcome [2] 0 0
Time to Progression (TTP) for Participants Who Had Progressive Disease - 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.
Timepoint [2] 0 0
Day 1 up to 14.4 months (max time to censoring)
Secondary outcome [3] 0 0
Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and 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.
Timepoint [3] 0 0
Day 1 up to Month 6 or Month 12
Secondary outcome [4] 0 0
Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and 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.
Timepoint [4] 0 0
Day 1 up to Month 6 or Month 12
Secondary outcome [5] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Maximum Observed Drug Concentration (Cmax) During Treatment Cycles 1 + 2
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Last (AUClast) During Treatment Cycles 1 + 2 - AUClast is the area under the serum concentration-time curve from time zero to time of last quantifiable concentration.
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Over the Dose Interval (AUCtau) During Treatment Cycles 1 + 2 - AUCtau is the area under the serum concentration-time curve over the dose interval tau, with tau equal to 21 days.
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Minimum Observed Drug Concentration (Cmin) During Treatment Cycles 1 + 2
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Terminal Elimination Half-life (t1/2z) During Treatment Cycles 1 + 2
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Volume of Distribution (Vz) During Treatment Cycles 1 + 2 - Volume of distribution observed at terminal phase after intravenous dosing.
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Drug Clearance (CL) During Treatment Cycles 1 + 2 - Drug clearance observed after intravenous dosing.
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
AMG 820 Pharmacokinetic Parameter by Dose Group: Accumulation Ratio (AR) - Accumulation ratio is AUCtau following administration in Cycle 2 / AUCtau after administration in Cycle 1
Timepoint [13] 0 0
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

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Belgium
State/province [8] 0 0
Wilrijk
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Germany
State/province [10] 0 0
Heidelberg
Country [11] 0 0
Spain
State/province [11] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
A multi-center Phase 1b/2 study testing the combination of AMG 820 and pembrolizumab in
subjects with select advanced solid tumors.
Trial website
https://clinicaltrials.gov/show/NCT02713529
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications