In 17 first-line patients treated with the combination, the estimated two-year overall survival (OS) rate was 70% - Median OS was not reached at a median follow-up of 29 months and 10 patients remained on study
Majority of patients (64%) with an OS over 2 years received only the combination
The combination achieved a 29% overall response rate with a median duration of response of 24 months and a 71% disease control rate
First data showing clinical activity and manageable safety profile with a combination of two T cell engagers in a solid tumor
The Company is planning a Phase 2/3 randomized trial evaluating the combination in unresectable or metastatic uveal melanoma
(OXFORDSHIRE, England & RADNOR, PA & GAITHERSBURG, MD, US, November 6, 2026) Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, presented data from its Phase 1/2 trial evaluating brenetafusp alone and in combination with KIMMTRAK in HLA-A*02:01-positive patients with metastatic uveal melanoma (mUM), in a poster session at the 2026 Society for Immunotherapy of Cancer (SITC) Annual Meeting. The data will also be presented in an oral session on Saturday, November 7, at 3:45 p.m. ET.
KIMMTRAK and brenetafusp are ImmTAC molecules targeting gp100 and PRAME, respectively, with PRAME representing an established negative prognostic factor in mUM. KIMMTRAK is the first bispecific T cell receptor therapy to demonstrate survival benefit in a solid tumor and is the standard of care for HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma. Brenetafusp is an investigational candidate being evaluated in a range of tumors, including first-line cutaneous melanoma in the PRISM-MEL-301 Phase 3 trial. Adding brenetafusp to KIMMTRAK tests the hypothesis of whether the combination may improve outcomes in patients with HLA-A*02:01-positive mUM by increasing target engagement and enhancing T cell-mediated tumor killing.
“Immunocore continues to lead bispecific T cell engager innovation, having demonstrated the first overall survival benefit in metastatic uveal melanoma. We are now seeing the synergistic potential of combining two clinically active ImmTAC therapies. The 1- and 2-year overall survival data could be practice-changing, and I look forward to evaluating this combination in a randomized trial for patients with metastatic uveal melanoma,” said Dr. Omid Hamid, Chief of Research & Immuno-Oncology, Co-Director, Cutaneous Malignancy Program at The Angeles Clinic & Research Institute.
“These encouraging Phase 1 data suggest combining brenetafusp with tebentafusp may offer a meaningful new option for HLA-A*02:01-positive patients with metastatic uveal melanoma,” said Dr. Mohammed Dar, Executive Vice President, Clinical Development and Chief Medical Officer of Immunocore. “Building on our leadership with KIMMTRAK, we believe that targeting both gp100 and PRAME – a combined ImmTAC approach – offers the potential to deliver an even greater benefit for HLA-A*02:01-positive patients.”
At the June 2026 data cut-off, 22 patients with mUM had received clinically active doses of brenetafusp monotherapy and 26 had received brenetafusp plus tebentafusp. The Company believes that this is the first data showing clinical activity and a manageable safety profile for a combination of two T cell engagers in a solid tumor.
Across the 17 evaluable first-line patients who received the combination, overall response rate (ORR) was 29% with a median duration of response (mDoR) of 24.1 months. The disease control rate (DCR) was 71% and median progression-free survival (mPFS) was 8.1 months. At the data cut-off, median overall survival (mOS) had not been reached at a median follow-up of 29 months. OS rates were 88% at one year and 70% at two years with 10 of the 17 patients remaining on study. The majority of patients with OS >2 years (64%; 7 out of 11) had received only the brenetafusp and tebentafusp combination.
In the 16 evaluable patients who received brenetafusp monotherapy in the second-line or later setting, ORR was 19%, mDoR 14.5 months, DCR 63%, mPFS 4.2 months, and mOS 20.3 months. OS rates were 63% at one year and 31% at two years.
The safety profile of brenetafusp as monotherapy and in combination with tebentafusp was generally well tolerated and consistent with that observed for the individual agents, with no new safety signals reported. The most frequent treatment-related adverse event (TRAE) was reversible and manageable cytokine release syndrome (CRS), observed in 77% of combination patients and 73% of monotherapy patients, with the majority being Grade 1 or 2 (no Grade 3/4 CRS for the combination and 5% Grade 3 CRS for brenetafusp monotherapy). Grade 3 or 4 TRAEs were reported in 38% of combination patients and 41% of monotherapy patients, with the most frequent being transient lymphocyte count decrease that resolved without intervention. No TRAE led to discontinuation or death in either group.
The data also demonstrated molecular responses for the combination. Out of the nine patients who were evaluable for ctDNA response, eight (89%) had a molecular response, and four (44%) achieved ctDNA clearance.
The Company is planning to start DUET-UVEAL, a randomized Phase 2/3 trial, to further evaluate the combination for the treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma.
The data presented at SITC come from an ongoing Phase 1/2 trial (NCT04262466; EudraCT 2019-004046-16) evaluating brenetafusp as monotherapy as well as in combination across a number of solid tumors, including HLA-A*02:01-positive patients with unresectable or metastatic uveal melanoma. Brenetafusp and tebentafusp were administered by weekly intravenous infusion with step-up dosing.
Presentation details
Title: Phase 1 evaluation of brenetafusp alone and in combination with tebentafusp in metastatic uveal melanoma (Abstract number: 1177)
Poster session: Poster Hall
Date and Time: Friday, November 6, 2026, 10:00 a.m. MST / 12:00 p.m. EST
Clinical oral abstract session: Session 2
Date and Time: Saturday, November 7, 2026, 1:45 p.m. MST / 3:45 p.m. EST
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About ImmTAC® molecules for cancer
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancer cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on demonstrated T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including tumors that are characterized as immune “cold” or having low mutation burden.
About the IMC-F106C-101 Phase 1/2 trial
IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumors, including non-small cell lung and ovarian cancers, as well as uveal melanoma, evaluating brenetafusp both as monotherapy and in combination arms with standards-of-care. The Phase 1 dose escalation portion of the trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp) both as monotherapy and in combination with standards-of-care. Brenetafusp is a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen.
About Uveal Melanoma
Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. This is the most common primary intraocular malignancy in adults and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.
About PRISM-MEL-301 (NCT06112314) – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma
The Phase 3 registrational trial is enrolling HLA-A*02:01-positive patients with previously untreated, advanced or metastatic cutaneous melanoma, with randomization to brenetafusp 160 mcg + nivolumab or a control arm of either nivolumab or nivolumab + relatlimab. The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR).
About KIMMTRAK
KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma.
IMPORTANT SAFETY INFORMATION
Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK, with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.
Skin Reactions
Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.
Elevated Liver Enzymes
Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.
Embryo-Fetal Toxicity
KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.
The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.
For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).
About Immunocore
Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including clinical and pre-clinical programs in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK, has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in 39 countries, including the United States, European Union, Canada, Australia, and the United Kingdom.
Forward Looking Statements
This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “may”, “will”, “believe”, “expect”, “plan”, “anticipate”, “aim”, “continue”, “target” and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding the expected efficacy and safety profile of brenetafusp, alone and in combination with KIMMTRAK; timing of the presentation of clinical trial data; the therapeutic potential and expected clinical benefits of brenetafusp alone and in combination with KIMMTRAK; plans to initiate a randomized Phase 2/3 trial evaluating brenetafusp in combination with KIMMTRAK in HLA-A*02:01-positive adults with unresectable or mUM; and expectations regarding the development of the Company’s pipeline. Any forward-looking statements are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to, preliminary, interim and top-line clinical trial results may not be indicative of, and may differ from, final clinical data; clinical trial data are subject to differing interpretations and assessments, including by regulatory authorities; the impact of worsening macroeconomic conditions, including as a result of health epidemics or pandemics, war in Ukraine, the conflict in the Middle East, or global geopolitical tension, on the Company’s business, financial position, strategy and anticipated milestones, including the Company’s ability to conduct ongoing and planned clinical trials; the Company’s ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products; the Company’s ability to obtain and maintain regulatory approval of KIMMTRAK and its other product candidates; the Company’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; the Company’s ability to successfully expand the approved indications for KIMMTRAK or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; the Company’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; the Company’s need for and ability to obtain additional funding, on favorable terms or at all, including as a result of changes in inflation and interest rates and unfavorable general market conditions; the Company’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any of its product candidates it or its collaborators are developing; and the success of the Company’s current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section titled "Risk Factors" in the Company’s filings with the Securities and Exchange Commission, including the Company’s most recent Annual Report on Form 10-K for the year ended December 31, 2025 filed with the Securities and Exchange Commission on February 25, 2026, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the SEC. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information, except as required by law.
Contact Information
Immunocore
Sébastien Desprez, Vice President, Communications
T: +44 (0) 7458030732
E: sebastien.desprez@immunocore.com
Follow on LinkedIn: @Immunocore
Ryan Baker, Vice President, Investor Relations
T: +1 (215) 384-4781
E: ryan.baker@immunocore.com
