Sponsor: Immunocore Ltd (industry)
Phase: 3
Start date: June 5, 2024
Planned enrollment: 680
Brenetafusp (IMC-F106C; PRAME-A02) is an investigational cancer immunotherapy. Human results have been reported from an early-phase study, chiefly in previously treated melanoma and platinum-resistant ovarian cancer. A phase 3 trial is evaluating it with nivolumab in advanced cutaneous melanoma; its clinical benefit has not yet been established in a randomized trial. (ascopubs.org)
Brenetafusp is a bispecific T-cell engager. Its engineered T-cell receptor recognizes a fragment of the cancer-associated protein PRAME displayed by HLA-A*02:01 on a cell, while its other component binds CD3 on T cells to redirect them toward that cell. This HLA requirement limits the population eligible for the reported trials. (dfhcc.harvard.edu)
In a 2026 conference abstract reporting 66 previously treated patients with advanced melanoma who received brenetafusp alone, the objective response rate was 12% and the disease-control rate (response or stable disease) was 52%. In the 24-patient group receiving a 160-microgram target dose, the respective rates were 17% and 67%. A separate 10-patient group receiving brenetafusp plus pembrolizumab had a 20% response rate. These small, nonrandomized groups cannot establish whether one dose or combination is superior. (ascopubs.org)
A 2024 conference abstract in platinum-resistant ovarian cancer reported 2 partial responses among 28 evaluable patients (7%) receiving brenetafusp alone, with disease control in 17 of 28 (61%). Three of 12 evaluable patients receiving brenetafusp with chemotherapy had partial responses. (s3.eu-central-1.amazonaws.com)
In the melanoma abstract, grade 1–2 cytokine-release syndrome occurred in 56% of patients in the 40-microgram group and 42% in the 160-microgram group; rash occurred in 44% and 42%, respectively. Grade 3–4 events occurred in 25% and 54%, mainly transient decreases in lymphocytes. In the ovarian-cancer abstract, grade 1–2 cytokine-release syndrome was the most common adverse event, occurring in 53% with brenetafusp alone and 80% with chemotherapy. These findings remain preliminary. (ascopubs.org)
Last updated: Sep 2026
Goal: Determine whether brenetafusp plus nivolumab improves progression-free survival compared with nivolumab-based regimens as first-line treatment for advanced melanoma.
Patients: Adults with HLA-A*02:01-positive, unresectable stage III or stage IV melanoma, measurable disease, known BRAF V600 status, and ECOG performance status 0–1. Prior systemic therapy for unresectable or metastatic melanoma is not permitted. Key exclusions include active or symptomatic CNS metastases, active autoimmune disease requiring immunosuppression, and significant cardiac or pulmonary disease.
Design: Randomized, controlled phase 3 trial comparing two brenetafusp dose levels plus nivolumab against an active comparator of nivolumab alone or nivolumab plus relatlimab.
Treatments: Brenetafusp is given weekly for 13 weeks, every 2 weeks through week 51, then every 4 weeks, with nivolumab every 4 weeks. It is an investigational bispecific T-cell engager that recognizes PRAME peptides presented by HLA-A*02:01 and binds CD3 to redirect T cells toward tumor cells. In a small, nonrandomized study of previously treated melanoma, brenetafusp monotherapy produced a 12% objective response rate; its benefit in this first-line combination remains unestablished. The comparator is nivolumab 480 mg alone or nivolumab 480 mg plus relatlimab 160 mg, given every 4 weeks; these are immune-checkpoint inhibitor regimens.
Outcomes: The primary endpoint is progression-free survival by blinded independent central review using RECIST 1.1. Secondary measures include overall survival, objective response rate, adverse and serious adverse events, treatment modifications due to adverse events, brenetafusp pharmacokinetics and immunogenicity, health-related quality of life, and an exploratory association between intratumoral immune cells and progression-free survival.
Burden on patient: Burden is moderate to high, particularly during the first 13 weeks, when brenetafusp requires weekly treatment visits rather than the comparator’s every-4-week schedule. Pharmacokinetic blood draws before dosing and at 0.5 and 4 hours afterward on day 1 of weeks 1, 2, and 3 add time at the clinic. Participants also need HLA and tumor-tissue screening, response assessments, and long-term follow-up; a fresh tumor sample may be needed if archived tissue is inadequate.
Last updated: Sep 2026
Inclusion Criteria:
* Participants must be HLA-A\*02:01-positive
* Participants must have histologically confirmed Stage IV or unresectable Stage III melanoma
* Archived or fresh tumor tissue sample that must be confirmed as adequate
* Participants must have measurable disease per RECIST 1.1
* Participant must have BRAF V600 mutation status determined
* Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the study screening date until 5 months after the final dose of study intervention
Exclusion Criteria:
* Participants with a history of a malignant disease other than those being treated in this study
* Participants with untreated, active, or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis
* Hypersensitivity to IMC-F106C, nivolumab, relatlimab, or any associated excipients
* Participants with clinically significant pulmonary disease or impaired lung function
* Participants with clinically significant cardiac disease or impaired cardiac function
* Participants with active autoimmune disease requiring immunosuppressive treatment
* Participants with any medical condition that is poorly controlled or that would, in the Investigator's or Sponsor's judgment, adversely impact the participant's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results
* Participants who received prior systemic anticancer therapy for unresectable or metastatic melanoma
* Participants with a history of a life-threatening AE related to prior anti-PD-(L)1 or anti-LAG-3
Córdoba, X5008HHW, Argentina
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Boulogne-Billancourt, 92104, France
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Caen, 14000, France
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Marseille, Cedex, 13385, France
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Toulouse, Cedex, 31059, France
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Erfurt, 99089, Germany
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Frankfurt, 60590, Germany
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Minden, 32429, Germany
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Giessen, D-35392, Germany
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Bremen, 28205, Germany
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Dortmund, 44137, Germany
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Erlangen, 91054, Germany
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Essen, 45122, Germany
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Marburg, 35043, Germany
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Heidelberg, 69120, Germany
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Kiel, DE-24105, Germany
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Debrecen, Hungary
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Coimbra, 3004-561, Portugal
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Lisbon, 1099-023, Portugal
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Cluj-Napoca, 400015, Romania
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Craiova, 200542, Romania
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Iași, 700106, Romania
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A Coruña, 15006, Spain
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Barcelona, 08908, Spain
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Málaga, 29016, Spain
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Las Palmas de Gran Canaria, 35016, Spain
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Madrid, 28034, Spain
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Córdoba, 14004, Spain
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Seville, 41009, Spain
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Granada, 18014, Spain
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Seville, 41013, Spain
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Valencia, 46010, Spain
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San Sebastián, 20014, Spain
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Zaragoza, 50009, Spain
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Pamplona, 31008, Spain
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Valencia, 46026, Spain
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Santander, Cantabria, 39008, Spain
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Stockholm, 171 76, Sweden
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Jönköping, 553 05, Sweden
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Uppsala, SE75185, Sweden
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Zurich, 8901, Switzerland
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Çankaya, 6800, Turkey (Türkiye)
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Malatya, 44280, Turkey (Türkiye)
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Altındağ, 6230, Turkey (Türkiye)
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Seyhan, 1140, Turkey (Türkiye)
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Yenimahalle, 06170, Turkey (Türkiye)
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Cordaleo, İzmir, 35575, Turkey (Türkiye)
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Glasgow, G12 0YN, United Kingdom
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Manchester, M204BX, United Kingdom
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Liverpool, L78YA, United Kingdom
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Oxford, Ox37LE, United Kingdom
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Denver, Colorado, 80222, United States
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Aurora, Colorado, 80045, United States
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Washington D.C., District of Columbia, 20007, United States
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Jacksonville, Florida, 32224, United States
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Miami, Florida, 33136, United States
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Chicago, Illinois, 60611, United States
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Westwood, Kansas, 66205, United States
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Edgewood, Kentucky, 41017, United States
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Boston, Massachusetts, 02215, United States
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Detroit, Michigan, 04820, United States
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Minneapolis, Minnesota, 55407, United States
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Hackensack, New Jersey, 07601, United States
[email protected] / 551-996-1777
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Lake Success, New York, 11042, United States
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Columbus, Ohio, 43210, United States
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Philadelphia, Pennsylvania, 19107, United States
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Pittsburgh, Pennsylvania, 15232, United States
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Greenville, South Carolina, 29605, United States
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Spartanburg, South Carolina, 29303, United States
[email protected] / 864-530-6554
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Nashville, Tennessee, 37203, United States
No email / No phone
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Nashville, Tennessee, 37203, United States
[email protected] / 888-555-2835
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Knoxville, Tennessee, 37920, United States
No email / 865-305-6284
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Dallas, Texas, 75235-9179, United States
[email protected] / 214-645-9830
Status: Recruiting
Salt Lake City, Utah, 84112, United States
[email protected] / 801-213-8486
Status: Recruiting
Charlottesville, Virginia, 22903, United States
[email protected] / No phone
Status: Recruiting
Richmond, Virginia, 23298-0070, United States
[email protected] / 804-628-0616
Status: Recruiting
Seattle, Washington, 98104, United States
[email protected] / 206-215-3125
Status: Recruiting
Greenslopes, Queensland, 4120, Australia
No email / No phone
Status: Completed
Prague, 110 00, Czechia
No email / No phone
Status: Completed
Bobigny, 93000, France
No email / No phone
Status: Completed
Skorzewo, 60185, Poland
No email / No phone
Status: Completed
Bydgoszcz, 85796, Poland
No email / No phone
Status: Completed
London, W1G 6AD, United Kingdom
No email / No phone
Status: Completed
Palo Alto, California, 94304, United States
No email / No phone
Status: Completed
Farmington, Connecticut, 06030-2205, United States
No email / No phone
Status: Completed
St Louis, Missouri, 63110, United States
No email / No phone
Status: Completed
New York, New York, 10032, United States
No email / No phone
Status: Completed