brenetafusp (IMC-F106C) / Immunocore - LARVOL DELTA

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

Phase 1 monotherapy data in heavily pre-treated platinum resistant ovarian cancer patients (GlobeNewswire) - P1/2 | N=727 | NCT04262466 | Sponsor: Immunocore Ltd | "Brenetafusp was well tolerated with no treatment-related discontinuation or death observed. The most frequent treatment-related adverse event was reversible and manageable cytokine release syndrome, observed in 57% of patients, with the majority being Grade 1. Thirty-one of the 37 monotherapy patients were evaluable for RECIST v1.1 tumor assessment, 58% of whom demonstrated disease control (partial response and stable disease), including two confirmed partial responses (6.5% RECIST response rate). Of patients who had tumor progression, 64% were treated beyond progression (median of 2 additional months). Across all 37 patients, the median progression-free survival (PFS) was 3.3 months, and the overall survival (OS), while still maturing, was 73% at 6 months."

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

Immunocore reports second quarter financial results and provides a business update (GlobeNewswire) - "Phase 1/2 clinical trial of brenetafusp (PRAME-A02) in multiple solid tumors: The Company plans to present clinical data for brenetafusp in late-line non-small cell lung cancer (NSCLC) in the fourth quarter of 2024; IMC-T119C: Remain on track for regulatory submission of Investigational New Drug (IND) or Clinical Trial Application (CTA) for IMC-T119C in the fourth quarter of 2024; The CTA for IMC-R117C was accepted in April 2024 by the EMA, and the Phase 1 clinical trial is expected to start in the second half of 2024."

IND • New P1 trial • P1/2 data • Colorectal Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Immunocore reports updated Phase 1 data of brenetafusp (IMC-F106C), an ImmTAC bispecific targeting PRAME, in immune checkpoint pre-treated cutaneous melanoma patients at ASCO 2024 (Immunocore) - "'Brenetafusp continues to demonstrate promising monotherapy clinical activity in late-line cutaneous melanoma patients who were previously treated with checkpoint therapies,' said Dr. Omid Hamid...'The disease control and PFS benefit for these brenetafusp-treated melanoma patients compares favorably to data with other immunotherapies.'"

Media quote

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

A phase 3 trial of IMC-F106C (PRAME x CD3) plus nivolumab versus standard nivolumab regimens in HLA-A*02:01+ patients with previously untreated advanced melanoma (PRISM-MEL-301). (ASCO 2024) - P1/2, P3 | "T cell receptor (TCR) bispecifics have shown overall survival (OS) benefit with tebentafusp (gp100 ´ CD3) in a phase (Ph) 3 trial in metastatic uveal melanoma [1]...Subsequently, approximately 590 additional patients will be randomized to Arm (A or B) vs. control Arm C, either nivolumab monotherapy or nivolumab + relatlimab, dependent on the country...Ann Oncol 2022; 33 (Supp7): S875 Hamid et al. J Immunother Cancer 2023; 11(6): e006747."

Clinical • IO biomarker • Metastases • P3 data • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • BRAF • HLA-A • PRAME

Immunocore announces randomization of first patient in the global, registrational Phase 3 clinical trial testing brenetafusp for the treatment of first-line advanced or metastatic cutaneous melanoma (GlobeNewswire) - "Immunocore Holdings plc...announces randomization of the first patient in the PRISM-MEL-301 trial, assessing the efficacy and safety of brenetafusp (IMC-F106C; PRAME-A02), in combination with nivolumab, in first-line advanced or metastatic cutaneous melanoma....The Phase 3 trial (NCT06112314) will randomize HLA-A*02:01 positive patients with first-line, advanced or metastatic cutaneous melanoma to brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on country."

Trial status • Cutaneous Melanoma

Immunocore reports updated Phase 1 data of brenetafusp (IMC-F106C), an ImmTAC bispecific targeting PRAME, in immune checkpoint pre-treated cutaneous melanoma patients at ASCO 2024 (GlobeNewswire) - P1/2 | N=727 | NCT04262466 | Sponsor: Immunocore Ltd | "Monotherapy brenetafusp (IMC-F106C) in late-line cutaneous melanoma demonstrated promising disease control (partial response and stable disease), progression free survival (PFS), and ctDNA molecular response; Clinical activity was enriched in PRAME positive patients with 58% disease control rate and 4.2 months median PFS; Peripheral blood T cell fitness was associated with increased brenetafusp clinical activity and was higher in earlier lines of therapy; Brenetafusp is well tolerated as monotherapy and in combination with anti-PD1."

P1 data • Cutaneous Melanoma • Melanoma • Oncology

Immunocore announces upcoming presentation and posters at ASCO 2024 (GlobeNewswire) - "Immunocore Holdings plc...will present Phase 1 expansion data for brenetafusp (IMC-F106C)...in patients with late-line cutaneous melanoma...at the 2024 American Society of Oncology (ASCO) Annual Meeting commencing on 31 May....The Company will also present four posters, including one trial-in-progress poster of the Phase 3 PRISM-MEL301 trial with brenetafusp in combination with nivolumab versus standard nivolumab regimens in HLA-A*02:01+ patients with first-line advanced melanoma, and three posters sharing clinical and translational data about KIMMTRAK in metastatic uveal melanoma."

Clinical data • P1 data • Trial status • Cutaneous Melanoma • Melanoma • Oncology • Uveal Melanoma

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 | N=170 ➔ 727 | Trial completion date: Feb 2026 ➔ Jun 2026 | Trial primary completion date: Feb 2024 ➔ Jun 2026

Checkpoint inhibition • Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • HLA-A • PRAME

Immunocore reports fourth quarter and full year 2023 financial results and provides a business update (Immunocore Press release) - "Phase 1/2 clinical trial of IMC-F106C targeting PRAME-A02 in multiple solid tumors: The Company expects to report clinical data from the ongoing monotherapy and combination cohorts throughout 2024 including cutaneous melanoma (expected in Q2 2024), ovarian (expected by Q3 2024), and non-small cell lung carcinoma (expected by Q4 2024)."

P1/2 data • Cutaneous Melanoma • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Immunocore announces clinical trial collaboration and supply agreement with Bristol Myers Squibb to evaluate IMC-F106C (PRAME HLA-A02) in combination with nivolumab in its registrational Phase 3 first-line advanced cutaneous melanoma trial (GlobeNewswire) - "Immunocore Holdings plc...today announced that it has entered into a clinical trial collaboration and supply agreement with Bristol Myers Squibb...to investigate Immunocore’s ImmTAC bispecific TCR (T cell receptor) candidate targeting PRAME HLA-A02, IMC-F106C, in combination with Bristol Myers Squibb’s nivolumab, in first-line advanced cutaneous melanoma...Under the terms of the collaboration, Immunocore will sponsor and fund the registrational Phase 3 clinical trial of IMC-F106C in combination with nivolumab in first-line advanced cutaneous melanoma (PRISM-MEL-301), and Bristol Myers Squibb will provide nivolumab. The PRISM-MEL-301 trial will randomize HLA-A*02:01+ first-line advanced cutaneous melanoma patients to IMC-F106C + nivolumab....Immunocore plans to randomize the first patient in this trial in the first quarter of 2024."

Licensing / partnership • Trial status • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer • Solid Tumor

IMC-F106C Regimen Versus Nivolumab Regimens in Previously Untreated Advanced Melanoma (PRISM-MEL-301) (clinicaltrials.gov) - P3 | N=680 | Recruiting | Sponsor: Immunocore Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Melanoma • Oncology • Solid Tumor • BRAF • HLA-A

Immunocore announces strategic priorities and pipeline expansion ahead of 42nd Annual J.P. Morgan Healthcare Conference presentation (GlobeNewswire) - "Advancing our PRAME franchise in multiple solid tumors and broadening the addressable population. Randomization is expected to begin in the first quarter of 2024 in the registrational trial for IMC-F106C in first-line advanced cutaneous melanoma (PRISM-MEL-301), and we expect to present data from the Phase 1/2 clinical trial monotherapy and combination cohorts throughout 2024. We further expect to submit investigational new drug (IND) applications or clinical trial applications (CTA) for IMC-P115C (PRAME HLA-A2 Half-Life-Extended) and IMC-T119C (PRAME HLA-A24) candidates in 2024."

IND • New trial • P1/2 data • Trial status • Cutaneous Melanoma • Gynecologic Cancers • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Skin Cancer • Solid Tumor

AGC Biologics to Prepare Late-Phase and Commercial Runs for Immunocore (AGC Biologics Press Release) - "Today, we announced a new late-stage clinical and process performance qualification (PPQ) project at our Heidelberg, Germany site with Immunocore Holdings Plc...Immunocore intends to use the Heidelberg site to complete late-stage manufacturing and prepare for commercialization for IMC-F106C, Immunocore’s PRAME-targeted bispecific therapy....Under the agreement, AGC Biologics will leverage our microbial fermentation and manufacturing experience to perform bench-scale qualification and process characterization, and other required studies to support phase III manufacturing, as well as PPQ runs."

Licensing / partnership • Oncology

Immunocore Reports Third Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "PRISM-MEL301 – First PRAME Phase 3 trial with IMC-F106C in first-line cutaneous melanoma: The Company plans to randomize the first patient in this trial in the first quarter of 2024; Phase 1/2 IMC-F106C targeting PRAME-A02 in multiple solid tumors: The Company expects to report data from the trial in the first half of 2024."

P1/2 data • Trial status • Cutaneous Melanoma • Oncology • Solid Tumor