Immunocore presents updated Phase 1 data of brenetafusp in patients with heavily pretreated advanced melanoma
Immunocore presents updated Phase 1 data of brenetafusp in patients with heavily pretreated advanced melanoma
Brenetafusp monotherapy resulted in a 6-month overall survival rate of 87% and disease control rate of 52% in heavily pretreated HLA-A*02:01-positive patients with melanoma
Data support selection of 160 mcg dose for the ongoing Phase 3 PRISM-MEL-301 trial in first-line advanced melanoma
Clinical benefit was consistent across difficult-to-treat subgroups, including patients with primary PD-1 resistance
Brenetafusp was generally well tolerated as monotherapy and in combination with pembrolizumab
(OXFORDSHIRE, England & RADNOR, Penn. & GAITHERSBURG, Md., US, 31 May 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, today announced updated results from its Phase 1/2 trial evaluating brenetafusp in patients with heavily pretreated advanced melanoma. The data is presented in a poster at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
"I am pleased to present these updated brenetafusp data at ASCO. Patients with advanced melanoma who progress on anti-PD-1 therapy have limited options, and seeing meaningful disease control in heavily pretreated patients is genuinely promising. These results support continued evaluation of brenetafusp in advanced melanoma," said Professor Georgina Long, Medical Director, Melanoma Institute Australia, The University of Sydney.
"These data with brenetafusp in heavily pretreated advanced melanoma show consistent responses and survival even in those with poor prognosis, including patients with primary PD-1 resistance," said Mohammed Dar, Chief Medical Officer of Immunocore. "These data also reinforce our confidence in the potential of brenetafusp at the dose of 160 mcg in combination with nivolumab in first-line advanced melanoma, in the ongoing Phase 3 PRISM-MEL-301 trial."
Phase 1/2 efficacy data
In the 66 patients treated with brenetafusp monotherapy (target doses 20-320 mcg), the median overall survival (OS) was 14.3 months (95% CI: 11.3-20.4; median follow up of 22.4 months) with a landmark OS rate of 87% at 6 months and 57% at 12 months. The disease control rate (DCR = partial responses and stable diseases) was 52%, while the overall response rate (ORR) was 12%.
Multiple measures of clinical benefit (6-month OS, DCR, ORR, tumor reduction) were numerically higher for patients treated with the 160 mcg dose – despite worse baseline prognostic factors compared to those treated with 40 mcg. These data support selection of 160 mcg for the ongoing Phase 3 trial evaluating brenetafusp + nivolumab vs. standard nivolumab regimens (NCT06112314) in first-line advanced melanoma. The safety profile was similar at both doses.
Median OS was 14.7 months for patients with primary PD-1 resistance, defined as progression within 6 months of starting the first regimen containing anti-PD1. Despite these patients having primary PD-1 resistance, the median OS was similar to all monotherapy patients (14.3 months).
In exploratory analyses, circulating tumor DNA (ctDNA) response in patients with PD-1 primary resistance was numerically higher (53%; 8/15) compared to the overall group (38%; 19/50). Treatment outcome was not impacted by PD-L1 status and was shown, in this exploratory analysis, to be associated with tumor expression of beta 2 microglobulin – a protein involved in antigen presentation – and baseline peripheral blood T cell fitness, which has been shown to be better in earlier lines of therapy.
In the 10 patients treated with brenetafusp in combination with pembrolizumab, the data showed numerically higher ORR and DCR compared to monotherapy, with efficacy also reported in patients with PD-1 primary resistance.
Phase 1/2 safety data
Brenetafusp was generally well tolerated, showing a predictable, mechanism-driven safety profile as monotherapy and in combination. The most common treatment-related adverse events (TRAEs) (≥20%) – which were reversible and attenuated over time – included CRS (56%; predominantly low grade, reversible, and attenuated over time), rash (44%), pyrexia (44%), chills (38%), fatigue (31%), decreased lymphocyte count (38%), nausea (25%), and pruritus (44%). The most frequent Grade 3-4 TRAE was transient decreased lymphocyte count (25%). There were three TRAEs that led to treatment discontinuation (two monotherapy patients and one combination patient).
Phase 1/2 trial overview
The Phase 1/2 trial (NCT04262466; EudraCT 2019-004046-16) enrolled patients with unresectable or metastatic melanoma who were HLA-A*02:01-positive (central testing) and previously treated with anti-PD-(L)1 therapy. Brenetafusp was administered as a weekly IV infusion with step dosing to a target dose. Tumor response was assessed by RECIST every 9 weeks; ctDNA was assessed every three weeks.
Second poster: Effect of IL7 on T cell fitness and ImmTAC anti-tumor activity
In a second poster presented during ASCO 2026, the Company built on previously disclosed data regarding the importance of T cell fitness for the efficacy of ImmTAC molecules. The new data demonstrated the anti-tumor activity of these therapies may increase when combined with IL7 in vitro. This study showed that IL7 treatment expanded naïve/stem-like memory T cells, enhanced ImmTAC-mediated T cell induction of IFNγ secretion and tumor killing, as well as reduced immune checkpoint receptor expression and T cell exhaustion. Additionally, a single dose of IL7 resulted in a sustained increase in T cell fitness of cancer patients. Taken together, the in vitro and in vivo data are consistent with the hypothesis that a combination with IL7 may increase the anti-tumor activity of ImmTAC therapies.
Presentations details (ASCO 2026)
Title: Phase 1 evaluation of the PRAME-targeted ImmTAC brenetafusp in advanced melanoma (Mel). (Abstract number: 9527)
Session: Melanoma/Skin Cancers (Poster Board: 243)
Date and Time: May 31, 2026, 9:00 AM-12:00 PM CDT
Title: Effect of IL7 on ImmTAC-mediated killing by T cells in vitro and T cell fitness in patients (Abstract number: 2662)
Session: Developmental Therapeutics - Immunotherapy (Poster Board: 452)
Date and Time: May 30, 2026, 1:30 PM-4:30 PM CDT
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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 cancerous 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 the demonstrated mechanism of 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 immune "cold" low mutation rate tumors.
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 randomizing HLA-A*02:01-positive patients with previously untreated, advanced or metastatic cutaneous melanoma, 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 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. The Phase 1 dose escalation 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), a bispecific protein built on Immunocore's ImmTAC technology, and the Company's first molecule to target the PRAME antigen. The Company is currently focusing on enrolling patients in combination arms with standards-of-care across multiple tumor types.
About Cutaneous Melanoma
Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments.
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; the sufficiency of initial trial data to support the continued evaluation of brenetafusp in advanced melanoma; and the anticipated development of brenetafusp including timeline and expected future data readouts. 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 Immunocore'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; Immunocore'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 Immunocore'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 Immunocore's filings with the Securities and Exchange Commission, including Immunocore'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.
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