brenetafusp (IMC-F106C) / Immunocore - LARVOL DELTA

Results from phase I dose escalation of IMC-F106C, the first PRAME × CD3 ImmTAC bispecific protein in solid tumors (ESMO 2022) - P1/2 | "ImmTAC bispecifics redirect polyclonal T cells to target intra/extracellular cancer proteins, as validated by tebentafusp (tebe; gp100×CD3 ImmTAC) with an overall survival benefit in metastatic uveal melanoma (mUM). Conclusions IMC-F106C, the first PRAME×CD3 ImmTAC, is well tolerated and demonstrated durable RECIST partial responses and ctDNA response in PRAME+ pts across multiple tumor types. Dose escalation and multiple expansions are ongoing."

IO biomarker • P1 data • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • Uveal Melanoma • CTLA4 • HLA-A • PRAME

Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM). (ASCO 2024) - P1/2, P3 | "Stable disease (SD) with any tumor reduction confirmed with ≥ 1 subsequent scan was analyzed based on association with overall survival (OS) for tebentafusp...Pembrolizumab (pembro) dosed at IV 400 mg Q6W... IMC-F106C was well tolerated with promising clinical activity in ICI-pretreated, mCM patients without clinical options. Clinical activity, measured by any confirmed tumor reduction and ctDNA molecular response, is enriched in PRAME+ patients at ~40% and associated with longer PFS and OS. IMC-F106C can be combined with anti-PD1."

Clinical • IO biomarker • P1 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • HLA-A • PRAME

Phase 1 evaluation of the PRAME‑targeted ImmTAC brenetafusp in advanced melanoma (Mel). (ASCO 2026) - P1/2, P3 | "Funded by Immunocore Ltd Clinical Trial Registration Number: NCT04262466 Background: Brenetafusp (brene) is an ImmTAC bispecific (PRAME × CD3) therapy that promotes T cell recruitment into tumors. Brene shows promising monotherapy activity in late-line Mel, including difficult to treat populations, without causing ICI-like irAEs, and can be safely combined with pembro. Ph1 results support 160 mcg as the selected dose in the Ph3 PRISM-MEL trial evaluating brene with nivolumab versus standard nivolumab regimens (NCT06112314)."

IO biomarker • Metastases • P1 data • Cutaneous Melanoma • Melanoma • Solid Tumor • B2M • BRAF • GPR183 • HLA-A • PD-L1 • PRAME

ICANS or not? A patient case with neurological symptoms during treatment with brenetafusp and nivolumab. (ADO 2026) - No abstract available

Clinical

Phase 1/2 clinical trials of brenetafusp and IMC-P115C (PRAME-A02 Half-Life Extended) in multiple solid tumors (Immunocore Press release) - "After observing an initial brenetafusp monotherapy signal in platinum-resistant ovarian cancer (PROC), the Company is evaluating, as part of an ongoing Phase 1/2 trial, combination therapy with bevacizumab in earlier lines, including platinum-sensitive ovarian cancer (PSOC). In the same trial, the Company continues signal detection across multiple metastatic non-small cell lung cancer (NSCLC) cohorts, including combinations with standards of care in earlier-line NSCLC. The Company is enrolling patients in the Phase 1 dose escalation trial evaluating IMC-P115C in patients with multiple solid tumors. The Company expects to present Phase 1/2 data from both trials in the second half of 2026."

First-in-human • P1/2 data • Platinum resistant • Platinum sensitive • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor

Testing the Anti-Cancer Drug, Brenetafusp (IMCF106C), in Rare Cancers (clinicaltrials.gov) - P2 | N=42 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P2 trial • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • PRAME

Effect of IL7 on ImmTAC-mediated killing by T cells in vitro and T-cell fitness in patients. (ASCO 2026) - P1/2, P2 | "Funded by Immunocore Ltd Background: A blood T cell fitness (TCF) signature, reflecting properties of naïve and stem cell memory T cells, was strongly associated with clinical benefit from tebentafusp (gp100 × CD3) and brenetafusp (PRAME × CD3) ImmTAC bispecific therapies¹...The proportion of TCF high patients increased from 36% at baseline to 93% post NTI7 monotherapy... Despite repeated antigen stimulation in vitro, IL7 sustained naïve/memory T cells, enhanced ImmTAC‑redirected T cell cytotoxicity and IFNγ production, and reduced T cell exhaustion. A single dose of rhIL7 resulted in a sustained increase in TCF signature and converted patients with low TCF signature into high TCF. These findings support combination with IL7 as a rational strategy to augment T cell fitness and potentially improve efficacy of ImmTAC bispecific T cell therapies."

Preclinical • Breast Cancer • Eye Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Uveal Melanoma • CD28 • GPR183 • IFNG • IL7 • IL7R • LXN • PRAME

Immunocore presents updated Phase 1 data of brenetafusp in patients with heavily pretreated advanced melanoma (GlobeNewswire) - "The data is presented in a poster at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting....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%....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)."

P1 data • Melanoma

The Company will present the following two posters at the 2026 American Society of Clinical Oncology Meeting (GlobeNewswire)

Clinical • P1 data • Melanoma

PRAME portfolio (GlobeNewswire) - "The Company is enrolling HLA-A*02:01 positive patients with first-line, advanced or metastatic cutaneous melanoma to brenetafusp 160 mcg + nivolumab or a control arm of either nivolumab or nivolumab + relatlimab...The Company continues to evaluate brenetafusp in a Phase 1/2 trial in combination in platinum-resistant ovarian cancer (PROC) and in earlier lines of platinum-sensitive ovarian cancer (PSOC). In the same trial, the Company continues signal detection in metastatic NSCLC cohorts, including combination in earlier-line NSCLC; The Company is enrolling patients in the Phase 1 dose escalation trial evaluating IMC-P115C in patients with multiple solid tumors; The Company expects to present Phase 1/2 data from both trials in the second half of 2026."

P1/2 data • Platinum resistant • Platinum sensitive • Trial status • Cutaneous Melanoma • Ovarian Cancer • Solid Tumor

IMC-F106C-101: Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors (clinicaltrials.gov) - P1/2 | N=410 | Active, not recruiting | Sponsor: Immunocore Ltd | Recruiting ➔ Active, not recruiting | N=727 ➔ 410 | Trial completion date: Aug 2026 ➔ Dec 2027 | Trial primary completion date: Feb 2026 ➔ Oct 2026

Checkpoint inhibition • Enrollment change • Enrollment closed • First-in-human • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • PRAME

Shared PRAME epitopes are T-cell targets in NUT carcinoma. (PubMed, J Immunother Cancer) - "PRAME is highly and frequently expressed in NUT carcinoma, and the most common oncoprotein causing NUT carcinoma, BRD4::NUTM1, contributes to these high PRAME levels. PRAME epitopes presented by HLA class I are a previously unrecognized therapeutic vulnerability for NUT carcinoma that warrants clinical trials testing PRAME-targeted immunotherapies in this neglected patient population."

IO biomarker • Journal • Head and Neck Cancer • Lung Cancer • NUT Midline Carcinoma • Oncology • Solid Tumor • BRD3 • BRD4 • HLA-A • NSD3 • NUTM1 • PRAME

PRAME programs (The Manila Times) - "Second half of 2026: Present data from Phase 1/2 brenetafusp combinations in ovarian, including platinum sensitive ovarian cancer; Second half of 2026: Present data from Phase 1/2 brenetafusp monotherapy and combinations in NSCLC; Second half of 2026: Present initial data from Phase 1 trial with IMC-P115C (PRAME-A02-HLE) in multiple solid tumors; Continue enrollment in Phase 3 brenetafusp combination trial in 1L cutaneous melanoma (PRISM-MEL-301)."

Clinical data • Platinum sensitive • Cutaneous Melanoma • Melanoma • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor

PRISM-MEL-301 – First PRAME Phase 3 clinical trial with brenetafusp in first-line advanced cutaneous melanoma (GlobeNewswire) - "The Independent Data Monitoring Committee (IDMC) has recommended the dose of 160 mcg as the go-forward dose in PRISM-MEL-301, the Company’s registrational Phase 3 trial in first-line, advanced cutaneous melanoma; The IDMC made the decision following a pre-planned review of safety for all three arms and of efficacy for the two brenetafusp regimens (40 mcg and 160 mcg) in the first 90 patients randomized in the Phase 3 trial. (In 1Q 2025, the IDMC reviewed the safety of the first 30 patients randomized and recommended to continue the study with no changes.); Patients treated with the dose of 160 mcg will be included in the intent-to-treat analysis for the primary endpoint; Patients who are receiving 40 mcg have the option to dose-escalate to 160 mcg but will not be included in the intent-to-treat analysis for the primary endpoint."

DSMB • Cutaneous Melanoma

Immunocore reports second quarter financial results and provides a business update (GlobeNewswire) - "KIMMTRAK (tebentafusp-tebn) net revenues of $98.0 million in Q2 2025, growing by 30% year-over-year; Phase 3 TEBE-AM trial on track to complete enrollment in 1H 2026; Dose selection for PRISM-MEL-301 Phase 3 trial expected in 2H 2025; Phase 1 single ascending dose HBV data for IMC-I109V will be presented at the 2025 AASLD Liver Meeting."

Enrollment status • P1 data • Sales • Trial status • Hepatocellular Cancer • Melanoma • Uveal Melanoma

PRAME Epitopes are T-Cell Immunovulnerabilities in BRD4::NUTM1 Initiated NUT Carcinoma. (PubMed, bioRxiv) - "NC is one of the most aggressive solid tumors to afflict humans and is refractory to chemotherapy, T-cell checkpoint blockade, and targeted therapies. We show PRAME epitopes are promising targets for TCR-based therapeutics like brenetafusp in NC, adding to growing momentum for addressing challenging fusion malignancies with TCR therapeutics."

IO biomarker • Journal • NUT Midline Carcinoma • Oncology • Solid Tumor • BRD4 • NUTM1 • PRAME

Immunocore reports fourth quarter and full year 2024 financial results and provides a business update (GlobeNewswire) - "The Company is currently enrolling the TEBE-AM registrational Phase 3 trial and expects to complete enrollment in the first half of 2026....The Company randomized the first patient in the registrational Phase 3 clinical trial evaluating brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab for HLA-A*02:01 patients with first-line, advanced or metastatic cutaneous melanoma. Selection of the go-forward dose by the independent data monitoring committee is expected in the second half of 2025."

Trial status • Cutaneous Melanoma

IMC-F106C Regimen Versus Nivolumab Regimens in Previously Untreated Advanced Melanoma (PRISM-MEL-301) (clinicaltrials.gov) - P3 | N=680 | Recruiting | Sponsor: Immunocore Ltd | Trial primary completion date: Dec 2026 ➔ Oct 2027

Metastases • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF • HLA-A

IMC-F106C-101: Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors (clinicaltrials.gov) - P1/2 | N=727 | Recruiting | Sponsor: Immunocore Ltd | Trial primary completion date: Jun 2026 ➔ Feb 2026

Trial primary completion date • Oncology • Solid Tumor • HLA-A • PRAME

Phase 1 safety and efficacy of brenetafusp, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM) (SITC 2024) - P1/2, P3 | "Pembrolizumab (pembro) was dosed IV 400 mg Q6W...All mono patients received prior ICI (100% anti-PD1, 81% ipilimumab)...A Phase 3 trial of brenetafusp with nivolumab in first-line mCM has been initiated (PRISM-MEL-301; NCT06112314). Ethics Approval The study was approved by the Institutional Review Board/Independent Ethics Committee of each study site and followed the Declaration of Helsinki and International Conference on Harmonisation Good Clinical Practice guidelines. All patients provided written informed consent before any study procedures were performed."

Clinical • IO biomarker • P1 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • HLA-A • PRAME

Single cell analysis of a T cell fitness signature associated with clinical benefit from brenetafusp, a PRAME x CD3 T cell engager (SITC 2024) - P1/2 | "Conclusions A TCF gene signature, which was associated with clinical benefit from ImmTAC T cell engagers, reflects T cells with high stemness and self-renewal capacity combined with increased co-stimulatory receptors and higher tumor homing potential. An active CD40/CD40L axis was associated with high TCF which is consistent with the hypothesis that epitope spread contributes to long term benefit from ImmTACs."

Clinical • IO biomarker • Oncology • CD2 • CD28 • CD40LG • CD8 • CXCR3 • HLA-A • PRAME

Phase I safety and efficacy of brenetafusp, a PRAME × CD3 ImmTAC T cell engager, in platinum resistant ovarian cancer (PROC) (ESMO 2024) - P1, P1/2, P1b, P1b/2a, P2 | "We present monotherapy (mono) and chemotherapy combination (CC) data in PROC, and association with a baseline blood T cell fitness (TCF) signature that was also linked with tebentafusp benefit in uveal melanoma (ESMO 2024)...Chemo options were gemcitabine (Gem), nab-paclitaxel (NP), and PLD... Brenetafusp was well tolerated, alone and with chemotherapy. Monotherapy was active in PROC, demonstrated by DCR and molecular response, which are surrogates of benefit for the ImmTAC platform. Clinical activity associated with blood TCF signature, which is another ImmTAC hallmark."

Clinical • P1 data • Eye Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • Uveal Melanoma • CD28 • HLA-A • PRAME

Association of a blood T cell fitness gene signature with clinical benefit from ImmTAC bispecific T cell engagers (ESMO 2024) - P1, P1/2, P1b, P1b/2a, P2 | "Background: Tebentafusp (tebe), an ImmTAC bispecific (gp100 x CD3), showed OS benefit in metastatic uveal melanoma (mUM). A second ImmTAC, brenetafusp (brene; PRAME x CD3), showed activity in several tumors... A blood T cell fitness signature that correlated with Tn/scm gene expression was strongly associated with tebe benefit. Association was confirmed with a second ImmTAC in mUM and in cutaneous melanoma (ASCO 2024) and ovarian cancer (ESMO 2024). Tn/scm may be an important determinant of ImmTAC benefit as described for other T cell therapies."

Clinical • Gene Signature • IO biomarker • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • Uveal Melanoma • CD28 • GPR183 • IL7R • PRAME • TCF7

Phase 1 chemotherapy combination data in heavily pre-treated platinum resistant ovarian cancer patients (GlobeNewswire) - P1/2 | N=727 | NCT04262466 | Sponsor: Immunocore Ltd | "In the Phase 1 trial, 16 patients with platinum-resistant ovarian cancer were treated with brenetafusp and either gemcitabine, nab-paclitaxel or pegylated doxorubicin chemotherapy...Sixty nine percent (9/13) of patients achieved disease control, including three partial responses (23% RECIST response rate)....Eleven of the 16 combination patients were evaluable for ctDNA response. The molecular response rate was 82% (9/11)."

P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

T cell fitness associated with clinical benefit across ImmTAC platform and in different tumor types (GlobeNewswire) - P1/2 | N=146 | NCT02570308 | P1/2 | N=727 | NCT04262466 | Sponsor: Immunocore Ltd | "In the KIMMTRAK cohort, patients with a TCF signature greater than or equal to the median had higher clinical activity compared to patients with a TCF signature below the median, respectively, including longer OS (28 months vs 11 months), PFS (5 months vs 2 months) and disease control (67% vs 36%). The association of TCF signature with longer OS was independent of known prognostic factors in uveal melanoma. In addition, the TCF signature was associated with greater tumor reduction and a higher rate of on-target, melanocyte-related adverse events; both are consistent with the mechanism action, and suggest that the signature is not purely prognostic."

Clinical data • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma