E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Colorectal cancer (CRC), pancreatic cancer or non-small cell lung cancer (NSCLC), and other indications dependent on emerging data |
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E.1.1.1 | Medical condition in easily understood language |
Advanced Pancreatic Cancer, Colorectal Cancer or Non-Small Cell Lung Cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049280 |
E.1.2 | Term | Solid tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | Pancreatic cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the safety and tolerability of AMG 820 administered in combination with pembrolizumab in subjects with select advanced solid tumors
Evaluate the objective response rate (ORR) of AMG 820 and pembrolizumab combination as per irRECIST in subjects with select advanced solid tumors |
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E.2.2 | Secondary objectives of the trial |
Evaluate the anti-tumor activity of AMG 820 and pembrolizumab combination in select advanced solid tumors by assessing
- ORR per RECIST1.1
- time to response (TTR), duration of response (DOR), and time to progression (TTP)
- progression free survival (PFS) and overall survival (OS) at 6 and 12 months
Characterize the pharmacokinetics (PK) of AMG 820 after intravenous (IV) infusion administration of AMG 820 in combination with pembrolizumab
Evaluate the relationship between the immune infiltrate status in pre-study tumor biopsies vs. clinical response |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 with 3 months prior to enrollment, when feasible.
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E.4 | Principal exclusion criteria |
- Has known active central nervous system metastases
- History of other malignancy with the past 2 years with some exceptions
- Subject has history of interstitial lung disease, (non-infectious) pneumonitis that required steroids, or current pneumonitis.
- History or evidence of other active autoimmune diseases that has required prolonged systemic treatment in past 2 years (ie, with use of disease modifying agents such as corticosteroids or immunosuppressive drugs).
- 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 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Dose limiting toxicities (DLT), treatment-emergent adverse events, treatment-related adverse events and clinically significant changes in vital signs, physical examinations, and clinical laboratory tests
- Objective response rate (ORR) per irRECIST in subjects treated at the recommended combination dose |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At 6 months: once the target enrollment is complete and each subject has been treated for at least 6 months or responded or withdrawn from the study, the analysis of the primary endpoints will occur.
2. At 12 months: once the target enrollment is complete and each subject has been treated for at least 12 months or has been followed up for PFS and OS for 12 months or withdrawn from the study, the analysis of primary and secondary endpoints (safety endpoints, ORR, PFS and OS at 6 and 12 months) will occur
Final Analysis - after all subjects have ended the study |
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E.5.2 | Secondary end point(s) |
- OR per RECIST 1.1; TTR, DOR and TTP; OS and PFS at 6 and 12 months
- PK parameters for AMG 820 including, but not limited to, maximum observed concentration (Cmax) and minimum observed concentration (Cmin). In addition, area under the concentration-time curve (AUC) and, if feasible, half-life (t1/2) for AMG 820.
- CD4, CD8 & CD68 cells number in fresh pre-treatment biopsies |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At 6 months: once the target enrollment is complete and each subject has been treated for at least 6 months or responded or withdrawn from the study, the analysis of the primary endpoints will occur.
2. At 12 months: once the target enrollment is complete and each subject has been treated for at least 12 months or has been followed up for PFS and OS for 12 months or withdrawn from the study, the analysis of primary and secondary endpoints (safety endpoints, ORR, PFS and OS at 6 and 12 months) will occur
Final Analysis - after all subjects have ended the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Primary Completion: is anticipated to occur when all Study Part 1 and 2 subjects have been enrolled and treated for at least 12 months, been followed up for PFS and OS at 12 months or discontinued from the study.
End of Trial: LSLV |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 3 |