Phase 1 Study of AMG 404 in Patients with Advanced Solid Tumours
Research type
Research Study
Full title
A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 404, a Programmed Death-1 (PD-1) Antibody, in Patients With Advanced Solid Tumors
IRAS ID
262257
Contact name
Tobias Arkenau
Contact email
Sponsor organisation
Amgen Ltd
Eudract number
2018-004268-80
Duration of Study in the UK
3 years, 6 months, 7 days
Research summary
Research Summary:
AMG 404 is an antibody that is made by identical immune cells that are all clones of a unique parent cell and works by activating an immune response against cancer. It blocks the activity of a molecule found in our bodies, called PD-1, that prevents immune cells from recognising and attacking cancer cells.
Animal studies have shown no serious toxic effects of AMG 404.
This is a first in human study to determine the side effects and best dose of AMG 404 in treating patients with advanced solid tumours in approximately 42 participants across 4 groups of patients (cohorts) in different dose levels-- Cohort 1-240mg; Cohort 2—480mg, Cohort 3-Also 480 mg for confirming the efficacy of this dose and Cohort 4—1050mg to evaluate if this high dose can be given.
AMG 404 will be administered intravenously every 4 weeks in participants with advanced solid tumours continuing until disease progression, intolerance to study medication, consent withdrawal, or if up to 12 months participant achieves a complete response, and up to 24 months if participant shows partial response or stable disease.
During the study, the participants will undergo AMG 404 treatment, safety and research evaluation of the study product through their blood and urine samples, archival tumour blocks (fresh biopsy if archival samples are not available) and radiographic scans through CT or MRI (as appropriate).
Participants who have consented for this study and are above 18 years with advanced solid tumours would be eligible for the study. The study will last for 2.5 years.
The study will take place in Australia, Brazil, Belgium, Poland, France, UK, USA, Japan and South Korea.
In the UK, the study will take place at the Sarah Cannon Research Institute, 93, Harley Street, London, W1G 6ADSummary of Results:
1. Study Name Title of the Study: A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 404, a Programmed Death-1 (PD-1) Antibody, and AMG 404 in Combination With Other Cancer Therapies, in Patients With Advanced Solid Tumors Brief Title: AMG 404 in Patients With Advanced Solid Tumors Protocol Number: 20180143 EU Trial Number: 2018-004268-80 Other Identifiers: NCT03853109 Date of This Summary: 23 July 2024 What does this summary cover?
This summary shows the main results from one clinical study. The results are only for this study. Other studies may find different results. Researchers and health authorities look at the results of many studies to decide which medicines work best and are safest for patients.
Amgen has committed to make research results available to the public. This summary has been provided as part of that commitment and should not be used for any other purpose. It should not be considered to make a claim for any product or to guide treatment decisions.2. Who Sponsored This Study?
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799 USA
Phone (United States): +1 805-447-1000
Phone (United Kingdom): +44 1223 436441
Amgen Inc. is the sponsor of the study who made AMG 404, the medicine tested in the study. Amgen would like to thank everyone who participated in this study and feels it is important to share the results of this study.3. General Information About the Clinical Study Where and when was the study done?
• This study took place in Australia, Belgium, Brazil, Canada, Japan, Poland, Singapore, South Korea, Spain, Taiwan, Turkey, the United Kingdom, and the United States.
• The study began in March 2019 and ended in November 2023.
• The study was stopped earlier than planned for business strategy reasons. The study was not stopped because of safety reasons.
Why was the study done?
• This was a phase 1 study conducted as part of the early process to develop new medicines for humans to treat cancer. Researchers looked at how this medicine works in the body and the effect that it has in the body, including side effects.
• The main purpose of this study was to find out information about the safety of the study medicine AMG 404 alone and also in combination with other cancer therapies. To do this, researchers looked at:
- The number of participants who developed medical problems considered significant enough to stop any further increase in the dose of study medicine (called dose-limiting toxicities).
- The number of participants who developed adverse events at any time after being given their first dose of study medicine. An adverse event is any unwanted medical problem that may or may not have been caused by the study medicine.
- The number of participants who developed medical problems that the doctor thought could have been caused by the study medicine.
- Changes in vital signs (eg, blood pressure and heart rate) and clinical laboratory tests (eg, blood and urine tests).
• The study was stopped early for business strategy reasons. AMG 404 was not given in combination with other cancer therapies in this study as originally planned.4. Who Was Included in This Study?
Who took part in the study?
This study included 171 participants with advanced solid tumors, including cancers of the digestive system, chest, head, neck, reproductive system, soft tissue, and kidney. 79 participants (46%, or about 46 out of 100) were women and 92 participants (54%, or about 54 out of 100) were men. They ranged in age from 26 to 84 years. 103 participants (60%, or about 60 out of 100) were younger than 65 years old and 68 participants (40%, or about 40 out of 100) were older than 65 years. This study took place at 34 study centers across Australia, Belgium, Brazil, Canada, Japan, Poland, Singapore, South Korea, Spain, Taiwan, Turkey, the United Kingdom, and the United States. The numbers of participants in each country are listed below:
• Australia: 30
• Belgium: 20
• Brazil: 9
• Canada: 12
• Japan: 13
• Poland: 25
• Singapore: 7
• South Korea: 10
• Spain: 4
• Taiwan: 1
• Turkey: 1
• United Kingdom: 9
• United States: 30
Participants were examined by a study doctor and chosen to be in the study if they:
• were 18 years or older
• had an advanced solid tumor5. Which Medicines Were Studied?
• AMG 404 is a type of medicine called an immunotherapy, which is designed to help the body’s immune system find and destroy cancer cells. AMG 404 blocks a type of protein (called programmed cell death protein 1) on the cell surface. Blocking this protein is thought to help the body’s immune system destroy cancer cells.
• AMG 404 was given once every 4 weeks by short-term intravenous infusion, where a tube is placed into a blood vessel (usually a vein in the participant’s arm) and the study medicine is given over a short period of time (30 minutes in this study).
• 3 of the 171 participants did not receive any study medicine and are not included in the side effects or results sections below. The remaining 168 participants received AMG 404.
• Participants were placed into 1 of 8 groups (called “cohorts”), numbered 1 to 4 and 6 to 9. Other cohorts numbered 5 and 10 to 13 were planned but never opened to participants. Cohorts were selected based on tumor type and were administered doses of AMG 404 as described below:
- Cohort 1: 3 participants were given low dose AMG 404.
- Cohort 2: 9 participants were given medium dose AMG 404.
- Cohort 3: 20 participants were given medium dose AMG 404.
- Cohort 4: 21 participants were given high dose AMG 404.
- Cohort 6: 20 participants were given medium dose AMG 404.
- Cohort 7: 41 participants were given medium dose AMG 404.
- Cohort 8: 41 participants were given medium dose AMG 404.
- Cohort 9: 13 participants were given medium dose AMG 404.6. What Were the Side Effects?
What is a side effect?
All medicines can cause side effects, or unwanted medical problems that may happen when you take a medicine. In this study, doctors reported all the medical problems participants had. Doctors believed some of the problems could have been caused by the study medicine(s). These possible side effects are listed below.
What side effects were seen?
The table below shows how many participants had side effects.
Side Effects During the Study
How many participants had serious side effects?
How many participants had non-serious side effects?
How many participants died from side effects?
How many participants stopped taking the study medicine because of side effects?
Cohort 1 AMG 404 low dose (3 participants)
0 participants (0%)
1 participant (33%)
0 participants (0%)
0 participants (0%)
Cohort 2 AMG 404 medium dose (9 participants)
1 participant (11%)
5 participants (56%)
0 participants (0%)
1 participant (11%)
Cohort 3 AMG 404 medium dose (20 participants)
1 participant (5%)
8 participants (40%)
0 participants (0%)
0 participants (0%)
Cohort 4 AMG 404 high dose (21 participants)
0 participants (0%)
15 participants (71%)
0 participants (0%)
0 participants (0%)
Cohort 6 AMG 404 medium dose (20 participants)
1 participant (5%)
13 participants (65%)
0 participants (0%)
1 participant (5%)
Cohort 7 AMG 404 medium dose (41 participants)
3 participants (7%)
33 participants (81%)
1 participant (2%)
1 participant (2%)
Cohort 8 AMG 404 medium dose (41 participants)
4 participants (10%)
26 participants (63%)
0 participants (0%)
1 participant (2%)
Cohort 9 AMG 404 medium dose (13 participants)
2 participants (15%)
8 participants (62%)
0 participants (0%)
1 participant (8%)
Total (All cohorts) (168 participants)
12 participants (7%)
109 participants (65%)
1 participant (1%)
5 participants (3%)If a participant, for example, had to stay in the hospital or died because of a side effect, the doctor reported that the side effect was serious.
13 serious side effects were reported in this study. Each serious side effect was reported in 1 out of 168 participants (1%):
• Brain swelling with usually temporary effects such as headache, changes in vision, reduced consciousness and seizures was reported in 1 out of 9 participants (11%) in cohort 2.
• Low red blood cell count was reported in 1 out of 20 participants (5%) in cohort 3.
• Inflammation of intestines related to the immune system was reported in 1 out of 20 participants (5%) in cohort 6.
• Cancer that spread to the spine was reported in 1 out of 41 participants (2%) in cohort 7. The participant passed away following spread of cancer to the spine.
• Inflammation of the lung was reported in 1 out of 41 participants (2%) in cohort 7.
• Underactive thyroid gland was reported in 1 out of 41 participants (2%) in cohort 7.
• Adrenal gland not working properly was reported in 1 out of 41 participants (2%) in cohort 8.
• Difficulty breathing was reported in 1 out of 41 participants (2%) in cohort 8.
• Inflammation of liver related to the immune system was reported in 1 out of 41 participants (2%) in cohort 8.
• Lack of oxygen in body tissues was reported in 1 out of 41 participants (2%) in cohort 8.
• Queasy/feeling like you need to throw up was reported in 1 out of 41 participants (2%) in cohort 8.
• Inflammation of large intestine was reported in 1 out of 13 participants (8%) in cohort 9.
• Loss of muscle control/coordination was reported in 1 out of 13 participants (8%) in cohort 9.9 non-serious side effects occurred in at least 5% of participants (or about 5 out of
100) in this study:
• Tiredness was reported in 28 out of 168 participants (17%):
o 2 out of 20 participants (10%) in cohort 3
o 6 out of 21 participants (29%) in cohort 4
o 3 out of 20 participants (15%) in cohort 6
o 6 out of 41 participants (15%) in cohort 7
o 9 out of 41 participants (22%) in cohort 8
o 2 out of 13 participants (15%) in cohort 9
• Itching was reported in 18 out of 168 participants (11%):
o 1 out of 3 participants (33%) in cohort 1
o 3 out of 21 participants (14%) in cohort 4
o 4 out of 41 participants (10%) in cohort 7
o 8 out of 41 participants (20%) in cohort 8
o 2 out of 13 participants (15%) in cohort 9
• Queasy/feeling like you need to throw up was reported in 15 out of 168 participants (9%):
o 2 out of 9 participants (22%) in cohort 2
o 2 out of 21 participants (10%) in cohort 4
o 2 out of 20 participants (10%) in cohort 6
o 2 out of 41 participants (5%) in cohort 7
o 6 out of 41 participants (15%) in cohort 8
o 1 out of 13 participants (8%) in cohort 9
• Underactive thyroid gland was reported in 15 out of 168 participants (9%):
o 1 out of 9 participants (11%) in cohort 2
o 2 out of 20 participants (10%) in cohort 3
o 3 out of 21 participants (14%) in cohort 4
o 2 out of 20 participants (10%) in cohort 6
o 4 out of 41 participants (10%) in cohort 7
o 3 out of 41 participants (7%) in cohort 8
• Fever was reported in 13 out of 168 participants (8%):
o 1 out of 20 participants (5%) in cohort 3
o 1 out of 21 participants (5%) in cohort 4
o 2 out of 20 participants (10%) in cohort 6
o 8 out of 41 participants (20%) in cohort 7
o 1 out of 13 participants (8%) in cohort 9
• Loss of appetite was reported in 13 out of 168 participants (8%):
o 1 out of 20 participants (5%) in cohort 3
o 1 out of 21 participants (5%) in cohort 4
o 2 out of 20 participants (10%) in cohort 6
o 1 out of 41 participants (2%) in cohort 7
o 5 out of 41 participants (12%) in cohort 8
o 3 out of 13 participants (23%) in cohort 9
• Rash was reported in 11 out of 168 participants (7%):
o 1 out of 21 participants (5%) in cohort 4
o 5 out of 41 participants (12%) in cohort 7
o 3 out of 41 participants (7%) in cohort 8
o 2 out of 13 participants (15%) in cohort 9
• Loose stools were reported in 10 out of 168 participants (6%):
o 2 out of 20 participants (10%) in cohort 3
o 1 out of 21 participants (5%) in cohort 4
o 1 out of 20 participants (5%) in cohort 6
o 2 out of 41 participants (5%) in cohort 7
o 4 out of 41 participants (10%) in cohort 8
• Joint pain was reported in 9 out of 168 participants (5%):
o 2 out of 21 participants (10%) in cohort 4
o 1 out of 20 participants (5%) in cohort 6
o 3 out of 41 participants (7%) in cohort 7
o 3 out of 41 participants (7%) in cohort 8
This section only shows the most often reported side effects considered by the study doctor as related to study medicine. No single clinical study can give a complete picture of the benefits and risks of a medicine. Information about other side effects may be available at the websites listed at the end of this summary.7. What Were the Overall Results of the Study?
• No dose-limiting toxicities were reported in this study.
• 167 out of 168 participants (99%) had at least 1 adverse event after receiving the first dose of study medicine.
• 110 out of 168 participants (65%) had at least 1 possible side effect.
• 1 out of 168 participants (1%) died of a possible side effect (cancer that spread to the spine).
• More results may be available at the websites listed at the end of this summary.8. How Has This Study Helped Participants and Researchers?
What else is important to know about these results?
These results are only for this clinical study, which looked at a sample of 171 people with advanced solid tumors. Not all participants in the study had the same results. The results for any single participant could have been better or worse than the results for their group. Other studies may find different results. These results do not explain how a study medicine may work in a single person. Many studies are needed to show the benefits and risks of a medicine that is still being tested. This research may help future participants and families by helping doctors understand more about the study medicine being studied.9. Are There Plans for Further Studies?
If more clinical studies are done, they may be listed on public websites, such as those below. Search for study medicine name AMG 404 on the websites below.10. Where Can I Find More Information About This Study?
To find out more about this study, check these websites:
- https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Coxfordb.rec%40hra.nhs.uk%7Cfac9289398e3400c136d08dcff36b1af%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638665857582171568%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=7SuMOa6MjuP9uUtlUfqKs2np44cY2K3Ex0FrJszhzhg%3D&reserved=0. Use the study identifier 2018-004268-80.
- https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Coxfordb.rec%40hra.nhs.uk%7Cfac9289398e3400c136d08dcff36b1af%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638665857582187210%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=QGFoOGfhy9tEAQvoWTEY9ZnkOTsfMpAhA2tsn8RUujo%3D&reserved=0.REC name
South Central - Oxford B Research Ethics Committee
REC reference
19/SC/0252
Date of REC Opinion
18 Jun 2019
REC opinion
Further Information Favourable Opinion