The study of AMG 160 in combination with other therapies for mCRPC
Research type
Research Study
Full title
A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC) Subprotocol A: A Phase 1b Study Evaluating the Safety and Efficacy of AMG 160 in Combination With Enzalutamide in Subjects With Metastatic Castration-resistant Prostate Cancer (mCRPC). Subprotocol B: A Phase 1b Study Evaluating the Safety and Efficacy of AMG 160 in Combination With Abiraterone in Subjects With Metastatic Castration-resistant Prostate Cancer (mCRPC). Subprotocol C: A Phase 1b/2 Study Evaluating the Safety and Efficacy of AMG 160 + AMG 404 and AMG 404 Monotherapy in Subjects With Metastatic Castration Resistant Prostate Cancer (mCRPC).
IRAS ID
285061
Contact name
Johann De Bono
Contact email
Eudract number
2020-001305-23
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 4 months, 29 days
Research summary
This study is a master protocol evaluating the safety and efficacy of therapies for metastatic castration-resistant prostate cancer (mCRPC).Prostate cancer is the second most frequent (after lung cancer) in men worldwide, counting 1276106 new cases and causing 358989 deaths (3.8% of all deaths caused by cancer in men) in 2018. In prostate cancer expression of PSMA (prostate specific membrane antigen) increases with disease progression and is highest in metastatic (development of secondary malignant growth from primary site of cancer) disease and strong correlation between negative prognosis and cell surface expression of PSMA. AMG 160 is a type of protein being used to stimulate the body’s immune system to kill cancer cells. In a Phase 1 first-in-human study, AMG 160 monotherapy demonstrates safety and tolerability with evidence of durable efficacy in late-line mCRPC population. Two novel therapies, enzalutamide and abiraterone, have demonstrated significant survival benefits in mCRPC patients. AMG 404 is a type of protein that binds to a protein called PD-1, which blocks immune cells from destroying cancer cells. Because the PD-1 protein is found at high levels in certain cancers, combining AMG 160 with AMG 404 may result in greater tumour killing. Therefore in this Phase 1b master protocol, the combination of AMG 160 with enzalutamide, abiraterone and AMG 404 (PD-1 inhibitor) will be evaluated in an earlier line of mCRPC population. To understand the contribution of AMG 404 to the efficacy of the combination, a cohort of subjects will participate in AMG 404 monotherapy study under sub-protocol C. Male subjects (≥ 18 years of age) with mRCPC will be eligible. This study will last approx. 3 years across 30 sites globally (US, Canada, Australia, Germany, Sweden, Denmark, Italy, France, Netherlands, Belgium, Spain and UK). 30 subjects to enrol globally for sub-protocol A and B and 45 for C.
Lay Summary of Results
Unless noted otherwise, the results presented below include all adverse events regardless of whether or not the doctors believed they could have been caused by the study medicine(s).
• Medical problems considered significant enough to stop any further increase in the dose of the study medicine:
o Substudy A: 3 out of 14 participants (21%) had dose-limiting toxicities
o Substudy B: 1 out of 14 participants (8%) had dose-limiting toxicities
o Substudy C: 6 out of 15 participants (40%) had dose-limiting toxicities
• Adverse events at any time after being given the first dose of study medicine:
o Substudy A: All 14 participants (100%) had at least 1 adverse event; 10 out of 14 participants (71%) had serious adverse events. No participants had an adverse event that resulted in death.
o Substudy B: All 14 participants (100%) had at least 1 adverse event; 9 out of 14 participants (64%) had serious adverse events. No participants had an adverse event that resulted in death.
o Substudy C: Parts 1 and 2: All 15 participants (100%) had at least 1 adverse event; 11 out of 15 participants (73%) had serious adverse events. No participants had an adverse event that resulted in death. Part 3: All
10 participants (100%) had at least 1 adverse event; 1 out of 10 participants (10%) had a serious adverse event (prostate cancer) that resulted in death. This event was not considered to have been caused by the study medicine.
• Effect of AMG 404 on the participant’s cancer (Substudy C only):
o Of the 6 participants included in the analysis measuring the main effect of the study medicine on the participant’s cancer, there was no meaningful shrinkage of the tumor for any participants.
o Of the 5 participants included in the analysis measuring the main effect of the study medicine on the participant’s circulating tumor cells, 1 participant (20%) had a response.o Of the 10 participants included in the analysis measuring the main effect of
the study medicine on the participant’s prostate specific antigen (PSA),
2 participants (20%) had a reduction in PSA by at least 30. Both of these participants (20%) had a reduction in PSA by at least 50% and 1 (10% overall) of these participants also had a reduction in PSA by at least 90%.
• There were no meaningful changes in vital signs and clinical laboratory tests related to the study medicines in any of the substudies.
• Treatment in all substudies was generally safe and tolerable.
• 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 these clinical substudies, which looked at a small sample of people with mCRPC. Not all participants in the substudies 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 160 on the websites below.
10. Where Can I Find More Information About This Study?
To find out more about this study, check these websites:
• EU Clinical Trials Information System https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7C886def7ad8234ffe969908dce216e3df%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638633835141430488%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=4CptYuviQfMLF%2BsVfBBEhIVMRnal%2BLucFmSK%2BQJ%2FXRE%3D&reserved=0. Use the study identifier 2020-001305-23.
• https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7C886def7ad8234ffe969908dce216e3df%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638633835141446473%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=OF7rM1%2BtSmCl9YCrEayBH8cwjmDb82bajmjAb5V4b3g%3D&reserved=0. Use the study identifier NCT04631601
If you participated in the study and have questions about the study results, the doctor or staff at your study center may be able to answer them.
Has the registry been updated to include summary results?: No
If yes - please enter the URL to summary results:
If no – why not?: Not yet, expected Oct 2025
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Pending
If yes, describe or provide URLs to disseminated materials:
If pending, date when dissemination is expected: 31/10/2025
If no, explain why you didn't follow it:
Have participants been informed of the results of the study?: Pending
If yes, describe and/or provide URLs to materials shared and how they were shared:
If pending, date when feedback is expected: 31/10/2025
If no, explain why they haven't:
Have you enabled sharing of study data with others?: No
If yes, describe or provide URLs to how it has been shared:
If no, explain why sharing hasn't been enabled: Consent for future research on participants’ study data is
always sought and Amgen will store this data after the end
of the study if consent is obtained. If in the future Amgen
approves a collaboration request involving the use of
participant study data, the appropriate privacy, ethical, and
legal measures would be taken to ensure compliance with
UK laws and regulationsHave you enabled sharing of tissue samples and associated data with others?: No
If yes, describe or provide a URL:
If no, explain why: Consent for future research on participants’ samples is
always sought and Amgen will store these samples after the
end of the study if consent is obtained. If a participant does
not consent to future research, samples will be destroyed
once all protocol-defined procedures are completed. If in
the future Amgen approves a collaboration request involving
the use of tissue samples from this trial, the appropriate
privacy, ethical, and legal measures would be taken to
ensure compliance with UK laws and regulationREC name
London - Surrey Borders Research Ethics Committee
REC reference
21/LO/0053
Date of REC Opinion
8 Mar 2021
REC opinion
Further Information Favourable Opinion