Sponsor: Immunocore Ltd (industry)
Phase: 3
Start date: June 5, 2024
Planned enrollment: 680
Brenetafusp (IMC-F106C; PRAME-A02) is an investigational, off‑the‑shelf, soluble T‑cell receptor (TCR)–CD3 bispecific (ImmTAC) that targets the cancer–testis antigen PRAME presented by HLA‑A02:01. It is in clinical development across multiple solid tumors, with a registrational Phase 3 trial in first‑line advanced cutaneous melanoma (PRISM‑MEL‑301) and an ongoing Phase 1/2 program including melanoma, ovarian, endometrial, and NSCLC cohorts. Patients must be HLA‑A02:01–positive and have PRAME‑expressing tumors. (immunocore.com)
Brenetafusp uses an affinity‑enhanced human TCR that recognizes an HLA‑A*02:01‑restricted PRAME peptide (SLLQHLIGL) fused to an anti‑CD3 effector domain. By binding PRAME–pHLA on tumor cells and CD3 on T cells, it redirects polyclonal T cells to kill PRAME‑positive cancer cells. Preclinical work shows highly sensitive, selective killing of PRAME+ targets across several tumor types and provides a rationale for combining with PD‑1 blockade. (pmc.ncbi.nlm.nih.gov)
Cutaneous melanoma (post‑checkpoint, Phase 1/2) - Monotherapy: Among evaluable patients, disease control rate (DCR) 56–61%; objective response rate (ORR) ~11–13%; confirmed tumor reduction in ~28–42% depending on analysis set. Clinical benefit was enriched in PRAME‑positive tumors. Median PFS ~4.2–4.5 months in PRAME‑positive vs ~2.1 months in PRAME‑negative; 6‑month OS ~94–95% vs 40%. ctDNA molecular response in ~41–42% and associated with longer PFS/OS. (ascopubs.org, immunocore.com) - Combination with anti‑PD‑1 (pembrolizumab, small cohort): 4/7 evaluable achieved disease control, including 1 confirmed partial response; ctDNA responses in 3/4 evaluable. (immunocore.com)
Ovarian cancer (platinum‑resistant, Phase 1/2) - Monotherapy: In heavily pretreated, high‑grade serous PROC, DCR ~58–61% with ORR 6–7%; median PFS ~3.3 months; 6‑month OS ~73%. ctDNA molecular response ~24–31% and associated with longer PFS/OS. Activity was higher in patients with a favorable baseline “T‑cell fitness” blood signature. (oncologypro.esmo.org, mskcc.org, immunocore.com) - Combination with chemotherapy (gemcitabine, nab‑paclitaxel, or pegylated doxorubicin): DCR ~67–69% with ORR ~23–25% in evaluable patients; ctDNA molecular response reported in ~82–90% of evaluable patients. (oncologypro.esmo.org, mskcc.org)
Ongoing/Planned trials - Phase 3 PRISM‑MEL‑301 (first‑line advanced/metastatic cutaneous melanoma): brenetafusp + nivolumab versus country‑specific control (nivolumab or nivolumab + relatlimab). Primary endpoint: PFS by BICR. As of June 18, 2024, the first patient was randomized; dose‑selection readout by IDMC anticipated in 2H 2025 per company updates. (immunocore.com, nasdaq.com)
Across melanoma and ovarian Phase 1 cohorts, brenetafusp was generally well tolerated: - Most common treatment‑related adverse events: grade 1–2 cytokine release syndrome (CRS) and rash, typically during the first three doses; no grade ≥3 CRS reported in melanoma cohorts. (immunocore.com) - In ovarian cancer, monotherapy CRS was mostly grade 1; no treatment‑related discontinuations or deaths. Combination safety was consistent with the individual agents. (immunocore.com, oncologypro.esmo.org) - In a small melanoma combination cohort, one dose‑limiting transaminitis occurred in a patient with prior checkpoint inhibitor–induced autoimmune hepatitis. (immunocore.com)
Last updated: Sep 2025
Goal: To determine whether adding the PRAME‑targeted TCR/CD3 bispecific brenetafusp (IMC‑F106C) to nivolumab improves outcomes versus contemporary PD‑1–based regimens (nivolumab or nivolumab plus relatlimab) in previously untreated, HLA‑A*02:01–positive advanced melanoma.
Patients: Adults with histologically confirmed unresectable stage III or stage IV melanoma, HLA‑A*02:01–positive, measurable disease by RECIST 1.1, ECOG 0–1, and known BRAF V600 status. Key exclusions include prior systemic therapy for advanced melanoma, active or untreated CNS metastases, clinically significant pulmonary or cardiac disease, active autoimmune disease requiring immunosuppression, and hypersensitivity to study drugs.
Design: Global, randomized, controlled, phase 3 study with parallel arms. Allocation is randomized; dose selection between two brenetafusp dose levels will occur within the experimental arms. Planned enrollment ~680 participants.
Treatments: Two experimental regimens: brenetafusp plus nivolumab. Brenetafusp is an investigational, off‑the‑shelf, soluble T‑cell receptor–CD3 bispecific (ImmTAC) that binds an HLA‑A*02:01‑restricted PRAME peptide on tumor cells and CD3 on T cells to redirect polyclonal T‑cell cytotoxicity. Early phase melanoma data show manageable safety with predominantly grade 1–2 cytokine release syndrome and rash, disease control rates around 56–61% and modest ORR as monotherapy post‑checkpoint; combination with PD‑1 blockade has shown preliminary disease control including partial responses. The control arm receives standard nivolumab 480 mg every 4 weeks or fixed‑dose nivolumab 480 mg plus relatlimab 160 mg every 4 weeks, consistent with approved PD‑1 or PD‑1/LAG‑3 regimens. Dosing schedules: brenetafusp weekly for 13 weeks, then every 2 weeks through Week 51, then every 4 weeks thereafter; nivolumab every 4 weeks in all arms.
Outcomes: Primary endpoint: progression‑free survival by blinded independent central review per RECIST 1.1. Key secondary endpoints include overall survival, overall response rate by BICR, safety (AEs, SAEs, and treatment modifications), pharmacokinetics (IMC‑F106C Cmax), anti‑drug antibodies, exploratory biomarker associations between intra‑tumoral immune contexture (CD3+/CD163+ ratio) and PFS in the IMC‑F106C arms, and health‑related quality of life. Follow‑up for efficacy up to approximately 45 months for PFS/response and 57 months for OS and safety.
Burden on patient: Moderate. Visit intensity is front‑loaded with weekly brenetafusp infusions for 13 weeks, then biweekly through one year before moving to every 4 weeks; control arm visits are every 4 weeks. Expect baseline and on‑study tumor assessments per RECIST at standard intervals, additional blood draws for safety labs, pharmacokinetics on early cycles (predose and multiple postdose timepoints during Weeks 1–3), and immunogenicity sampling. Archival or fresh tumor tissue is required, and exploratory biomarker work may necessitate adequate tissue, with possible optional biopsies. Travel and chair time are greater in the experimental arms during the first year relative to standard PD‑1 regimens, but otherwise procedures align with typical phase 3 oncology standards, without inpatient requirements anticipated for routine care.
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
Caba, Buenos Aires, 1213, Argentina
[email protected] / 541158216233
Status: Recruiting
Caba, Buenos Aires, C1430EGF, Argentina
[email protected] / 5491132682903
Status: Recruiting
Viedma, R8500ACE, Argentina
[email protected] / 542920601693
Status: Recruiting
Córdoba, X5008HHW, Argentina
[email protected] / 54 9 351 678-3938
Status: Recruiting
CABA, CP1426ANZ, Argentina
No email / No phone
Status: Recruiting
Waratah, New South Wales, 02298, Australia
[email protected] / (02) 40143280
Status: Recruiting
Greenslopes, Queensland, 4120, Australia
No email / No phone
Status: Completed
Nedlands, Western Australia, 06009, Australia
[email protected] / 61-8-6383 3189
Status: Recruiting
Nedlands, Western Australia, 06009, Australia
[email protected] / +61 8 6279 9466
Status: Recruiting
Woolloongabba, Australia
No email / No phone
Status: Recruiting
Wollstonecraft, Australia
No email / No phone
Status: Recruiting
North Melbourne, 3051, Australia
[email protected] / 61385595000
Status: Recruiting
Heidelberg, 3084, Australia
No email / No phone
Status: Recruiting
Graz, 8036, Austria
[email protected] / 43 31 638 580 169
Status: Recruiting
Salzburg, 5020, Austria
No email / No phone
Status: Recruiting
Pölten, Austria
No email / No phone
Status: Recruiting
Anderlecht, 01070, Belgium
[email protected] / 00 32 2 541 33 77
Status: Recruiting
Brussels, 1090, Belgium
[email protected] / 02 476 33 94
Status: Recruiting
Bruges, 8000, Belgium
[email protected] / 3250452849
Status: Recruiting
Brussels, 1200, Belgium
[email protected] / 32 276 48 509
Status: Recruiting
Leuven, 03000, Belgium
[email protected] / No phone
Status: Recruiting
Ijuí, Rio Grande do Sul, 98700-000, Brazil
[email protected] / 55 55 3195-0504
Status: Recruiting
Porto Alegre, Rio Grande do Sul, 90110-270, Brazil
[email protected] / +55 51-33072943
Status: Recruiting
Liberdade, 01509-010, Brazil
[email protected] / 2189-5000 (5138)
Status: Recruiting
Florianópolis, 88034-000, Brazil
[email protected] / +55 48 3331-1553
Status: Recruiting
Brasília, DF CEP 70200-730, Brazil
[email protected] / 55 61 2141 4856
Status: Recruiting
Barretos, 14784, Brazil
No email / No phone
Status: Recruiting
São Paulo, 15090-000, Brazil
[email protected] / +55 17 32015054
Status: Recruiting
Porto Alegre, 90035-903, Brazil
[email protected] / 55 51 3359-8619
Status: Recruiting
Porto Alegre, 90610-000, Brazil
[email protected] / 51 3320-3039
Status: Recruiting
Rio de Janeiro, 20220-410, Brazil
[email protected] / +55 (21) 99173-9618
Status: Recruiting
Rio de Janeiro, 22775-001, Brazil
[email protected] / +5521 96845-7879
Status: Recruiting
São Paulo, 01246-000, Brazil
No email / No phone
Status: Recruiting
São Paulo, 01308-070, Brazil
[email protected] / 11 9948-3000
Status: Recruiting
Fortaleza, 60135-237, Brazil
[email protected] / 55 85 30348677
Status: Recruiting
Sofia, 1527, Bulgaria
No email / No phone
Status: Recruiting
Panagyurishte, 4500, Bulgaria
[email protected] / 359888844526
Status: Recruiting
Plovdiv, 4000, Bulgaria
No email / No phone
Status: Recruiting
Sofia, Bulgaria
No email / No phone
Status: Recruiting
Toronto, Ontario, M5G 2C1, Canada
[email protected] / 416-946-4501
Status: Recruiting
Edmonton, T6G 1Z2, Canada
No email / 780-577-8082
Status: Recruiting
Olomouc, 77900, Czechia
[email protected] / (+420)588444295
Status: Recruiting
Hradec Králové, 500 05, Czechia
[email protected] / 42 0495834980
Status: Recruiting
Prague, 110 00, Czechia
[email protected] / 420737806453
Status: Recruiting
Herlev, 2730, Denmark
[email protected] / 004538362131
Status: Recruiting
Marseille, Cedex, 13385, France
No email / No phone
Status: Recruiting
Toulouse, Cedex, 31059, France
No email / No phone
Status: Recruiting
Lille, 59037, France
[email protected] / 0033320444193
Status: Recruiting
Nantes, France
No email / No phone
Status: Recruiting
Paris, 75010, France
No email / No phone
Status: Recruiting
Pierre-Bénite, 69310, France
No email / No phone
Status: Recruiting
Rouen, 76031, France
[email protected] / 0232886699
Status: Recruiting
Valence, 26000, France
No email / No phone
Status: Recruiting
Villejuif, 94800, France
No email / No phone
Status: Recruiting
Bobigny, 93000, France
No email / No phone
Status: Recruiting
Boulogne-Billancourt, 92104, France
No email / No phone
Status: Recruiting
Caen, 14000, France
[email protected] / 33234455050
Status: Recruiting
Dijon, France
[email protected] / 33380293842
Status: Recruiting
Munich, 81377, Germany
[email protected] / +4989440056326
Status: Recruiting
Würzburg, 97080, Germany
[email protected] / 4993120126762
Status: Recruiting
Leipzig, 4103, Germany
[email protected] / 00493419718600
Status: Recruiting
Minden, 32429, Germany
[email protected] / 57179054523
Status: Recruiting
Tübingen, 72076, Germany
[email protected] / 004970712985748
Status: Recruiting
Hamburg, 22045, Germany
[email protected] / 4941617036212
Status: Recruiting
Hamburg, 20246, Germany
[email protected] / 4940741057626
Status: Recruiting
Berlin, 10115, Germany
[email protected] / 4930450518448
Status: Recruiting
Giessen, D-35392, Germany
No email / (+)49641-985-43200
Status: Recruiting
Frankfurt, 60590, Germany
[email protected] / 4969630183115
Status: Recruiting
Essen, 45122, Germany
[email protected] / 02017232325
Status: Recruiting
Erfurt, 99089, Germany
[email protected] / 0361 781-4301
Status: Recruiting
Dresden, 01307, Germany
No email / 0049 351 458 19782
Status: Recruiting
Heidelberg, 69120, Germany
[email protected] / 496221568562
Status: Recruiting
Budapest, 1085, Hungary
[email protected] / +36-20-8258870
Status: Recruiting
Pécs, 7624, Hungary
[email protected] / 36303599887
Status: Recruiting
Szeged, 6720, Hungary
[email protected] / +36-303468499
Status: Recruiting
Meldola, 47014, Italy
No email / No phone
Status: Recruiting
Bari, 70124, Italy
No email / No phone
Status: Recruiting
Bergamo, 24125, Italy
No email / No phone
Status: Recruiting
Milan, 20141, Italy
[email protected] / No phone
Status: Recruiting
Milan, 20133, Italy
No email / No phone
Status: Recruiting
Napoli, 80131, Italy
No email / No phone
Status: Recruiting
Padua, 35128, Italy
No email / No phone
Status: Recruiting
Padua, I-35128, Italy
No email / No phone
Status: Recruiting
Perugia, 06129, Italy
No email / No phone
Status: Recruiting
Ponderano, 13875, Italy
No email / No phone
Status: Recruiting
Roma, 00128, Italy
No email / No phone
Status: Recruiting
Roma, 0168, Italy
No email / No phone
Status: Recruiting
Siena, 53100, Italy
No email / No phone
Status: Recruiting
Torino, 10126, Italy
No email / No phone
Status: Recruiting
Oslo, 0379, Norway
[email protected] / +47 452 59938
Status: Recruiting
Bergen, 05009, Norway
[email protected] / 4755972010
Status: Recruiting
Skorzewo, 60185, Poland
No email / No phone
Status: Completed
Warsaw, 02-781, Poland
[email protected] / 225462603
Status: Recruiting
Bydgoszcz, 85796, Poland
No email / No phone
Status: Recruiting
Gdansk, 80-214, Poland
[email protected] / No phone
Status: Recruiting
Cluj-Napoca, 400015, Romania
[email protected] / 40 745 364 514
Status: Recruiting
Iași, 700106, Romania
[email protected] / 40 746 110 096
Status: Recruiting
Craiova, 200542, Romania
[email protected] / 40723557512
Status: Recruiting
Santander, Cantabria, 39008, Spain
[email protected] / 942 20 33 51
Status: Recruiting
El Palmar, Murcia, 30120, Spain
[email protected] / 0034968369387
Status: Recruiting
Valencia, 46014, Spain
No email / No phone
Status: Recruiting
Valencia, 46026, Spain
[email protected] / 34 638 037 641
Status: Recruiting
Zaragoza, 50009, Spain
No email / No phone
Status: Recruiting
A Coruña, 15006, Spain
No email / No phone
Status: Recruiting
Barcelona, 08035, Spain
No email / No phone
Status: Recruiting
Barcelona, 08035, Spain
No email / No phone
Status: Recruiting
Barcelona, 08908, Spain
No email / No phone
Status: Recruiting
Barcelona, 8036, Spain
[email protected] / 0034687727943
Status: Recruiting
Córdoba, 14004, Spain
[email protected] / 957 002 343
Status: Recruiting
Madrid, 28009, Spain
[email protected] / 0034 914268161
Status: Recruiting
Granada, 18014, Spain
[email protected] / 0034 958 145 591
Status: Recruiting
Madrid, 28027, Spain
[email protected] / 0034 913 531 920
Status: Recruiting
Madrid, 28034, Spain
No email / No phone
Status: Recruiting
Madrid, 28041, Spain
[email protected] / 913908003
Status: Recruiting
Madrid, 28046, Spain
[email protected] / 917277516
Status: Recruiting
Madrid, 28050, Spain
No email / No phone
Status: Recruiting
Málaga, 29016, Spain
[email protected] / 0034 608093004
Status: Recruiting
Pamplona, 31008, Spain
[email protected] / 0034 948 296 666 + 2736
Status: Recruiting
Seville, 41009, Spain
[email protected] / 697958425
Status: Recruiting
Seville, 41013, Spain
No email / No phone
Status: Recruiting
Valencia, 46010, Spain
[email protected] / +34 961 973 517
Status: Recruiting
Stockholm, 171 76, Sweden
[email protected] / +46 08-123-717-91
Status: Recruiting
Gothenburg, SE41345, Sweden
No email / No phone
Status: Recruiting
Jönköping, 553 05, Sweden
[email protected] / 46102425943
Status: Recruiting
Lund, 22185, Sweden
No email / No phone
Status: Recruiting
Uppsala, SE75185, Sweden
No email / No phone
Status: Recruiting
Zurich, 8901, Switzerland
[email protected] / 41442552507
Status: Recruiting
Çankaya, Ankara, 06520, Turkey (Türkiye)
[email protected] / 0506 752 12 75
Status: Recruiting
Antalya, Campus, 07070, Turkey (Türkiye)
[email protected] / No phone
Status: Recruiting
Şehitkamil, Gaziantep, 27584, Turkey (Türkiye)
[email protected] / 0555 241 46 87
Status: Recruiting
Bahçelievler, Istanbul, 34180, Turkey (Türkiye)
No email / No phone
Status: Recruiting
Bornova, İzmir, 35100, Turkey (Türkiye)
[email protected] / 53 09 672 608
Status: Recruiting
Cordaleo, İzmir, 35575, Turkey (Türkiye)
[email protected] / 505 264 2353
Status: Recruiting
Altındağ, 6230, Turkey (Türkiye)
No email / No phone
Status: Recruiting
Seyhan, 1140, Turkey (Türkiye)
[email protected] / +90 533 361 69 39
Status: Recruiting
Yenimahalle, 06170, Turkey (Türkiye)
[email protected] / +90 536 640 10 20
Status: Recruiting
Samsun, 55270, Turkey (Türkiye)
[email protected] / 0532 599 28 25
Status: Recruiting
Malatya, 44280, Turkey (Türkiye)
[email protected] / 0533 572 01 75
Status: Recruiting
Çankaya, 6800, Turkey (Türkiye)
No email / No phone
Status: Recruiting
Ankara, 6100, Turkey (Türkiye)
[email protected] / +90 536 640 10 20
Status: Recruiting
London, W1G 6AD, United Kingdom
[email protected] / 0203 219 5200
Status: Recruiting
Liverpool, L78YA, United Kingdom
[email protected] / 01515565435
Status: Recruiting
Manchester, M204BX, United Kingdom
No email / No phone
Status: Recruiting
Surrey Quays, SM2 5PT, United Kingdom
No email / No phone
Status: Recruiting
Cambridge, CB20QQ, United Kingdom
No email / No phone
Status: Recruiting
Glasgow, G12 0YN, United Kingdom
[email protected] / 0141 301 7043
Status: Recruiting
Tucson, Arizona, 85720, United States
[email protected] / 520-621-2029
Status: Recruiting
Los Angeles, California, 90025, United States
[email protected] / 310-231-2181
Status: Recruiting
La Jolla, California, 92093-0698, United States
[email protected] / 858-822-6575
Status: Recruiting
Los Angeles, California, 90033, United States
[email protected] / 323-865-3935
Status: Recruiting
Santa Monica, California, 90404, United States
[email protected] / 310-582-7457
Status: Recruiting
Palo Alto, California, 94304, United States
[email protected] / 650-736-6425
Status: Recruiting
Los Angeles, California, 90095, United States
[email protected] / 310-794-3266
Status: Recruiting
Aurora, Colorado, 80045, United States
[email protected] / 720-848-9381
Status: Recruiting
Farmington, Connecticut, 06030-2205, United States
No email / No phone
Status: Recruiting
Washington D.C., District of Columbia, 20007, United States
No email / No phone
Status: Recruiting
Miami, Florida, 33136, United States
[email protected] / No phone
Status: Recruiting
Jacksonville, Florida, 32224, United States
[email protected] / 904-953-5323
Status: Recruiting
Chicago, Illinois, 60611, United States
No email / No phone
Status: Recruiting
Westwood, Kansas, 66205, United States
[email protected] / 913-945-7552
Status: Recruiting
Edgewood, Kentucky, 41017, United States
[email protected] / 859-301-4243
Status: Recruiting
Boston, Massachusetts, 02215, United States
[email protected] / 617-632-6704
Status: Recruiting
St Louis, Missouri, 63110, United States
No email / No phone
Status: Completed
Hackensack, New Jersey, 07601, United States
[email protected] / 551-996-1777
Status: Recruiting
New York, New York, 10032, United States
No email / No phone
Status: Completed
Lake Success, New York, 11042, United States
[email protected] / No phone
Status: Recruiting
Philadelphia, Pennsylvania, 19107, United States
[email protected] / 267-414-8820
Status: Recruiting
Pittsburgh, Pennsylvania, 15232, United States
[email protected] / 412-623-3544
Status: Recruiting
Greenville, South Carolina, 29605, United States
[email protected] / No phone
Status: Recruiting
Spartanburg, South Carolina, 29303, United States
[email protected] / 864-530-6554
Status: Recruiting
Nashville, Tennessee, 37203, United States
No email / No phone
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
Seattle, Washington, 98104, United States
[email protected] / 206-215-3125
Status: Recruiting