Immunocore presents promising data from Phase 1/2 trial cohort evaluating brenetafusp plus KIMMTRAK® (tebentafusp-tebn) in metastatic uveal melanoma

Immunocore plans a randomized Phase 2/3 study following combination results in 17 evaluable first-line patients.

Rhea-AI Summary

Immunocore (Nasdaq: IMCR) reported an estimated 70% two-year overall survival rate with brenetafusp plus KIMMTRAK in metastatic uveal melanoma. The ongoing Phase 1/2 trial included HLA-A*02:01-positive patients. Among 17 evaluable first-line combination patients, median overall survival was not reached after median follow-up of 29 months; 10 remained on study. Response rate was 29%, median response duration was 24 months, disease control was 71%, and median time without progression was 8.1 months.

Among 16 evaluable patients receiving brenetafusp alone after prior treatment, response rate was 19% and median overall survival was 20.3 months. Grade 3 or 4 treatment-related adverse events affected 38% of combination patients and 41% receiving monotherapy; none caused treatment discontinuation or death. Immunocore plans DUET-UVEAL, a randomized Phase 2/3 trial, to further evaluate the combination.

Positive

• Minor pointCombination estimated two-year overall survival was 70% among 17 evaluable first-line patients; one-year survival was 88%.
• Minor pointCombination median overall survival was not reached at median follow-up of 29 months; 10 patients remained on study.
• Minor pointCombination response rate was 29%, with median response duration of 24 months.
• Minor pointCombination disease control rate was 71% among evaluable first-line patients.
• Minor pointCombination median progression-free survival was 8.1 months, measuring time without disease progression.

10 minor points

• Minor pointCombination-only treatment accounted for 64% (7 out of 11) of patients surviving over two years.
• Minor pointBrenetafusp monotherapy response rate was 19% in 16 evaluable second-line or later patients.
• Minor pointMonotherapy median response duration was 14.5 months in second-line or later patients.
• Minor pointMonotherapy disease control rate was 63% in second-line or later patients.
• Minor pointMonotherapy median progression-free survival was 4.2 months in second-line or later patients.
• Minor pointMonotherapy median overall survival was 20.3 months; one-year and two-year survival rates were 63% and 31%.
• Minor pointCombination molecular responses occurred in eight of nine evaluable patients (89%), measuring circulating tumor DNA changes.
• Minor pointCombination circulating tumor DNA clearance occurred in four of nine evaluable patients (44%).
• Minor pointTreatment-related adverse events caused no discontinuations or deaths in either treatment group; no new safety signals emerged.
• Minor point. Forward-looking: it has not happened yet and may not happen.Immunocore plans DUET-UVEAL, a randomized Phase 2/3 trial, evaluating the combination in HLA-A*02:01-positive adults.

Negative

• Minor pointCombination Grade 3 or 4 treatment-related adverse events affected 38%; transient lymphocyte count decreases were most frequent.
• Minor pointMonotherapy Grade 3 or 4 treatment-related adverse events affected 41%; transient lymphocyte count decreases were most frequent.
• Minor pointCombination cytokine release syndrome affected 77%, with no Grade 3/4 cases; cases were reversible and manageable.
• Minor pointMonotherapy cytokine release syndrome affected 73%, including 5% Grade 3; cases were reversible and manageable.

Key Figures

First-line combination cohort: 17 patients Overall response rate: 29% Median duration of response: 24.1 months +5 more

First-line combination cohort

17 patients

Evaluable patients receiving brenetafusp plus tebentafusp

Overall response rate

29%

First-line combination cohort

Median duration of response

24.1 months

First-line combination cohort

Disease control rate

71%

First-line combination cohort

Median progression-free survival

8.1 months

First-line combination cohort

Two-year overall survival

70%

First-line combination cohort

Median overall survival

Not reached at 29 months median follow-up

First-line combination cohort

Grade 3 or 4 treatment-related adverse events

38%

Combination patients

Key Terms

overall response rate, median progression-free survival, cytokine release syndrome, ctdna, +2 more

6 terms

overall response rate medical

"overall response rate (ORR) was 29%"

Overall response rate is the percentage of patients in a clinical study whose measurable disease shrinks or disappears after receiving a treatment. Investors watch it like a product’s “hit rate” because higher response rates can signal a drug’s effectiveness, boost chances of regulatory approval and market demand, and affect a company’s future revenue prospects, similar to how a higher batting average suggests a more reliable player.

median progression-free survival medical

"median progression-free survival (mPFS) was 8.1 months"

Median progression-free survival is the length of time at which half of patients in a clinical study have not experienced disease worsening or progression. Think of it like the moment in a race when 50% of runners have not yet crossed a trouble line—it shows how long a therapy can delay disease activity for a typical patient. Investors use it as a straightforward signal of a drug’s effectiveness that can influence regulatory approval, market demand, and revenue potential.

cytokine release syndrome medical

"reversible and manageable cytokine release syndrome (CRS)"

An intense immune overreaction in which the body's defense system releases a large surge of signaling proteins, causing fever, low blood pressure, breathing trouble or organ stress; imagine the immune system's alarm going into overdrive and flooding the body with emergency responders. Investors care because this side effect can slow or block regulatory approval, increase clinical trial costs and liabilities, limit how widely a therapy can be used, and therefore affect a drug's market value and sales potential.

ctdna medical

"Out of the nine patients who were evaluable for ctDNA response"

Circulating tumor DNA (ctDNA) is tiny fragments of genetic material shed by cancer cells into the bloodstream, like breadcrumbs that can reveal a tumor’s presence and genetic makeup without needing a biopsy. For investors, ctDNA matters because tests and technologies that detect and analyze these fragments can speed diagnosis, track treatment response, and signal relapse, creating commercial opportunities in diagnostics, personalized therapies, and monitoring services.

maximum tolerated dose medical

"determine the maximum tolerated dose (MTD)"

Maximum tolerated dose is the highest amount of a substance, such as a medication or chemical, that can be used without causing unacceptable side effects or harm. It’s like finding the maximum speed you can drive without risking a ticket or accident. For investors, understanding this concept helps gauge how much risk or exposure is safe or sustainable in a given situation.

pharmacokinetics medical

"evaluate the safety, preliminary anti-tumor activity and pharmacokinetics"

Pharmacokinetics is the study of how a substance, such as a drug or chemical, moves through and is processed by the body over time. It tracks how it is absorbed, distributed, broken down, and eventually eliminated. For investors, understanding pharmacokinetics helps gauge the effectiveness, safety, and potential risks of new medications or treatments, which can influence a company’s success and valuation in the healthcare industry.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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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

###

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

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Immunocore's brenetafusp plus KIMMTRAK trial show in metastatic uveal melanoma?

Among 17 evaluable first-line patients, estimated two-year overall survival was 70% and response rate was 29%. Median overall survival had not been reached at median follow-up of 29 months. The trial evaluated patients with HLA-A*02:01-positive metastatic uveal melanoma.

What is Immunocore planning after the brenetafusp plus KIMMTRAK results?

Immunocore plans to start DUET-UVEAL, a randomized Phase 2/3 trial, evaluating the combination in HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma.

How were brenetafusp and KIMMTRAK administered in Immunocore's Phase 1/2 trial?

Brenetafusp and tebentafusp, marketed as KIMMTRAK, were administered by weekly intravenous infusion with step-up dosing. At the June 2026 data cut-off, 26 patients with metastatic uveal melanoma had received the combination and 22 had received clinically active doses of brenetafusp alone.