IMCgp100-202 Phase II Study in Advanced Uveal Melanoma
Research type
Research Study
Full title
A Phase II Randomized, Open-label, Multi-centre Study of the Safety and Efficacy of IMCgp100 Compared with Investigator's Choice in HLA-A*0201 Positive Patients with Previously Untreated Advanced Uveal Melanoma
IRAS ID
220229
Contact name
Paul Nathan
Contact email
Sponsor organisation
Immunocore Limited
Eudract number
2015-003153-18
Duration of Study in the UK
3 years, 3 months, 10 days
Research summary
Summary of Research
This research study is being conducted to find out whether IMCgp100, an experimental immunotherapy treatment for people with Advanced Uveal Melanoma, is safe and superiorly beneficial in terms of overall survival of patients who have uveal cancer compared to an Investigators choice of standard treatment. 327 patients will take part, 2/3 will receive IMCgp100 and 1/3 will receive their Investigator's choice of treatment. Recruitment is expected to take 16 months. Patients who take part will receive IMCgp100 treatment by an intravenous infusion on days 1, 8 and 15 of every 21 day treatment cycle. Patients who receive their Investigator's choice of treatment will receive their treatment once every 21 days. The study will look at what the body does to the drug as well as what the drug does to the body by taking and examining blood and urine samples and reviewing radiological scans. Tumour samples will also be examined from the start of the study and during the study should the patient agree to this optional aspect of the study to see how the drug is affecting the tumour tissue through treatment.Summary of Results
LAY SUMMARY OF CLINICAL TRIAL RESULTS
1. CLINICAL TRIAL IDENTIFICATION
EU CTR Number: 2024-517290-24
EudraCT: 2015-003153-18
Protocol Number: IMCgp100-202
Protocol Title: A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared with Investigator’s Choice in HLA-A*0201 Positive Patients with Previously Untreated Advanced Uveal Melanoma Study Title: Safety and efficacy of IMCgp100 versus Investigator’s Choice in advanced uveal melanoma
2. SPONSOR INFORMATION
Sponsor: Immunocore, Ltd.
Address: 92 Park Drive, Milton Park, Abingdon, Oxfordshire, OX14 4RY, United Kingdom
Telephone: +44 (0)1235 438600
Email: info@immunocore.com
Website: https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.immunocore.com%2F&data=05%7C02%7Cchelsea.rec%40hra.nhs.uk%7Cc73410c21c884271e59a08deebfe0184%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639207673356353303%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=qADl5bmG4%2BUCeEctwuhJtjrvDTOYSK2Pe1yYTXXlCYc%3D&reserved=0
3. GENERAL INFORMATION ABOUT THE CLINICAL TRIAL
This clinical trial studied advanced uveal melanoma, a rare cancer that starts in the eye and can spread to other parts of the body, primarily the liver.
The purpose was to determine whether tebentafusp, an immunotherapy, could help patients live longer and control the disease compared with standard treatments.
4. WHO PARTICIPATED
A total of 378 adult patients participated in this study across 14 countries.
All patients had advanced disease and had not received prior treatment for metastatic uveal melanoma.5. HOW THE TRIAL WAS CONDUCTED
Participants were randomly assigned (similar to flipping a coin) to receive tebentafusp weekly or standard treatment (pembrolizumab, ipilimumab, or dacarbazine) every 3 weeks. For every two people who got the new drug tebentafusp (given once a week), one person got the usual treatment (pembrolizumab, ipilimumab, or dacarbazine, given once every three weeks). Splitting people randomly this way helps make sure the groups are balanced, so the two treatments can be compared fairly, while letting more people receive the new drug.
The study was open-label, meaning both doctors and patients knew the treatment that was given.
6. RESULTS
Tebentafusp improved survival compared with standard treatment.
After 1 year, 73% of patients receiving tebentafusp were alive compared with 59% receiving standard treatment.
Initial (Primary) Results
The first analysis of the study showed that patients who received tebentafusp lived longer than those who received the standard treatments chosen by their doctor. On average, patients treated with tebentafusp lived about 21.7 months, compared with 16.0 months for patients receiving other treatments. This difference was large enough that researchers were confident it was due to the treatment rather than chance.
Three-Year Follow-up
Researchers continued to follow patients for three years after the study began. The results showed that the survival benefit of tebentafusp was maintained over time. Patients treated with tebentafusp continued to live longer on average than those who received the standard treatments (21.6 months versus 16.9 months), confirming that the benefit persisted with longer follow-up.
Five-Year Follow-up
After five years of follow-up, tebentafusp continued to show a lasting survival benefit. Patients treated with tebentafusp still lived longer on average than those who received the standard treatments (21.6 months versus 16.9 months). In addition, 16 out of every 100 patients treated with tebentafusp were alive five years after starting treatment, compared with 8 out of every 100 patients who received other treatments.
The survival benefit was seen across different patient groups, including those with more advanced disease. Some patients benefited even if their tumors did not shrunk or appeared to grow on scans.
7. SIDE EFFECTS
Common side effects included fever, rash, fatigue, nausea, chills, and low blood pressure.
A reaction called cytokine release syndrome where the immune system overreacts, often causing fever, chills, and low blood pressure happened often, but doctors were usually able to control it. Some patients did have serious side effects, but only a small number had to stop treatment because of them. Most of these side effects happened in the first few weeks of treatment and then became less frequent and less severe over time.
CONCLUSIONS
Tebentafusp helped people live longer and kept their cancer under control better than the standard treatments. Side effects were common but could be managed. Following patients for 5 years confirmed that this survival benefit lasts over time and that more people treated with tebentafusp were still alive at 5 years comparing to those who received standard treatments.
8. STUDY DATES
October 2017 to October 2020 (enrollment and treatment period) Patients were followed for survival for at least 5 years (through 2025) to evaluate long-term outcomes.
9. FURTHER INFORMATION
More information may be available from clinical trial registries such as ClinicalTrials.gov or EU CTIS, or from healthcare providers.REC name
London - Chelsea Research Ethics Committee
REC reference
17/LO/0497
Date of REC Opinion
21 Apr 2017
REC opinion
Favourable Opinion