Abstract talks
Explore our abstract talks below.
Session 1: Melanoma evolution
Abstract submission 16: Leah Pomfret: Lancaster University, Lancaster, United Kingdom
Investigating the role of primary cilia and the ciliome in melanoma phenotype switching
Background and aims
Melanoma has innate phenotypic plasticity, allowing switching between heterogenous cell phenotypes in response to immune and targeted therapies, therefore contributing to treatment resistance. These phenotypic subtypes closely resemble the differentiation trajectory from the early embryo, through the neural crest and embryonic melanoblasts, to differentiated melanocytes. Primary cilia are present on differentiated melanocytes, and loss is sufficient to drive cell cycle re-entry and metastatic melanoma progression.
Methods
To investigate ciliary and cell cycle parameters in melanoma cells we developed a cell and cilia cycle biosensor by fusing the Fucci(CA) probes hCdt1-mCherry and hGeminin-mVenus with cilia localised Arl13b-RFP670 allowing discrimination of the G1, S and and G2/M cell cycle phases and the primary cilium. We used PiggyBac to integrate our biosensor into melanoblast, melanocyte and a range of melanoma cell lines and observed ciliated cells in all of these cell types. In parallel we screened cilia associated genes for involvement in melanoma using the TCGA and melanoblast RNAseq data.
Results
We observed a higher mutation frequency in cilia associated genes for melanoma compared to other solid tumours, including breast, lung and ovarian cancer. Cilia length and number increased with the differentiation status of melanoma cell lines as determined by MITF expression. Differentiation trajectory analysis of TCGA melanoma data revealed a group of cilia genes specifically expressed in a predefined undifferentiated subtype, associated with an invasive phenotype. Our results suggest that ciliation status reflects melanoma differentiation status and that our new Arl13b-Fucci(CA) biosensor allows better cell cycle phase discrimination and tracking of cilia dynamics in these cells.
Conclusions
We conclude that the primary ciliome warrants further investigation for melanoma associated genetic variants that may influence melanoma phenotype switching.
Authors and affiliations
Leah Pomfret Lancaster University, Lancaster, United Kingdom; Louise Brennan University of Liverpool, Liverpool, United Kingdom; Emma Wilkinson Lancaster University, Lancaster, United Kingdom; Sarah Allinson Lancaster University, Lancaster, United Kingdom; Barbara Shih Lancaster University, Lancaster, United Kingdom; Richard Mort Lancaster University, Lancaster, United Kingdom
Abstract submission 19. Pakavarin Louphrasitthiphol: University of Oxford, Oxford, United Kingdom
To be or not to be: invasive melanoma’s survival strategy
Emerging approaches targeting circulating tumour cells (CTCs) that seed metastases by enhancing patients’ anti-cancer immunity and antibody-directed nanoparticles rely on cancer-specific or cancer-associated antigens. We aim to target CTCs through an alternative, yet largely unexplored, approach by promoting the activation of regulated cell death pathways that respond to heightened stress while cancer cells are in transit.
Proliferative to invasive phenotype switch in melanoma is characterised by downregulation of the melanocyte-inducing transcription factor (MITF) and concomitant upregulation of the neuronal-specific transcription factor, BRN2, a recognised driver of invasion and metastasis. This proliferative to invasive switch is driven by the highly conserved integrated stress response (ISR), which is activated by diverse stressors including reactive oxygen species, endoplasmic reticulum stress, and anoikis encountered by circulating tumour cells (CTCs). Sustained ISR activation promotes transcriptional induction and heterodimerisation of its principal effector ATF4 with the downstream target CHOP, thereby orchestrating pro-apoptotic gene expression. To persist under circulatory stress, CTCs must maintain cellular stress below the threshold that triggers cell death. Although BRN2 has been implicated in promoting melanoma survival, its role in modulating ISR-driven cell death remains unresolved.
We employed a combination of genomic and molecular biology assays to interrogate the functional crosstalk between ATF4 and BRN2 in melanoma cell survival. Our results revealed a direct role for BRN2 in modulating ATF4 activity.
Interfering with BRN2-ATF4 interaction led to precarious induction of apoptotic genes, a vulnerability that may be exploited to promote apoptosis of invasive melanoma cells under circulatory stress or in response to therapeutic stressors such as BRAF inhibition.
Authors and affiliations
Pakavarin Louphrasitthip, University of Oxford, Oxford, United Kingdom; Colin Goding, University of Oxford, Oxford, United Kingdom
Session 3: Melanoma-host interactions
Abstract submission 5: Lutong An: Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute, Manchester, United Kingdom
The impact of ageing on melanoma metastasis
Background
Older age is associated with increased solid organ metastases and melanoma mortality. Ageing and cancer are complex overlapping biological processes. Ageing drives metabolic alterations that confer survival advantages to tumour cells and alter immune function. Immunosenescence and inflammageing further impair cytotoxic responses and promote an immunosuppressive milieu. Although age-associated factors in the primary tumour microenvironment have been shown to promote melanoma metastasis, the broader impact in distant metastatic sites remains poorly defined. We aimed to study the systemic and organ-specific age-associated metabolites and immune alterations and their contribution to melanoma metastatic growth.
Methods
To study the natural ageing process, tissues from young and aged healthy female C57BL/6 mice were collected for targeted and untargeted proteomics, metabolomics, lipidomics, bulk RNA sequencing, and spectral flow cytometry. Age-matched female mice were also injected intravenously with murine melanoma cells to assess metastatic burden.
Results
We investigated the healthy young and aged lung and liver parenchyma, identifying potential premetastatic niches by age using multiomic analyses. Proteomics, metabolomics, lipidomics, and transcriptomics of the healthy lung and liver reveal unique metabolic profiles, including perturbations in major biological pathways such as glycolysis and lipid metabolism by age. Spectral flow cytometry reveals age-specific alterations in the immune landscape in the lung and liver, suggesting that ageing drives unique immune-metabolic environments that could promote melanoma seeding and metastatic outgrowth. Critically, intravenous murine melanoma models show that ageing enhances lung melanoma tumour burden. Our preliminary data indicate the aged tumour immune microenvironment is more suppressive than the young microenvironment. We are using spatial biology to explore the immune-metabolic interactions in young and aged human and mouse melanoma metastasis.
Conclusion
Our data suggest that ageing changes the solid organ metabolic and immune landscape, which impacts melanoma cell outgrowth and host survival.
Authors and affiliations
Lutong An; Karthik Mallela; Isabella Mataloni; Vanessa Parietti; Noah Palombo; Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute, Manchester, United Kingdom; Amaya Virós, Skin Cancer and Ageing Lab, Cancer Research UK Manchester Institute, Manchester, United Kingdom and Department of Dermatology, Salford Royal NHS Foundation Trust, Manchester, United Kingdom
Abstract submission 33: Jose L. Orgaz: Universidad Carlos III de Madrid, Department of Neuroscience and Biomedical Sciences, Getafe, Spain
Actomyosin signalling and phenotypic transitions in cutaneous melanoma and during adaptation to MAPK-targeted therapy
Abstract
Drug-tolerant persister (DTP) melanoma cells emerge within days of MAPK blockade with BRAF+MEK inhibitors (BMi). DTPs adapt to therapy mostly through non-genetic mechanisms that drive phenotypic transitions towards distinct differentiation states, contributing to drug resistance and patient relapse. Understanding the underlying signalling may reveal approaches to prevent therapy adaptation.
Non-muscle myosin II (NMII) forms contractile actomyosin filaments that contribute to cell invasion and metastasis. Previous studies have described NMII overactivation in BRAFi-resistant melanomas. However, whether and how NMII signalling contributes to BMi adaptation is unknown.
Melanoma cell lines and patient-derived melanoma cultures were treated with BMi, and NMII activity was assessed by immunoblotting and immunofluorescence, and by immunohistochemistry in tumour allografts from mice. Cell survival was evaluated by crystal violet staining of 2D cultures and by 3D spheroids. Protein depletion was achieved by RNAi.
We find that de-differentiating melanomas undergo actomyosin signalling rewiring as an early adaptive response to BMi. In seven melanoma models, dedifferentiating cells increased NMII activity within 1-14 days of BMi treatment, and this was confirmed in vivo in tumour allografts. Conversely, hyper-differentiating melanomas did not over-activate NMII, partly due to MITF. Functionally, co-targeting NMII with BMi impaired DTP survival in several models.
We also assessed whether NMII regulators from other systems (ROCK, MLCK, and others) control NMII in therapy-naïve melanomas. Knockdown of these proteins led to differing effects on NMII activity and cell survival in some models, suggesting distinct phenotype-specific sets of NMII regulators and associated vulnerabilities. Directly targeting NMII also caused diverse effects on cell survival and phenotype switching.
In summary, we identify actomyosin signalling as a phenotype-dependent adaptive mechanism in DTPs. Additionally, complex NMII regulatory networks operate in melanoma, suggesting novel therapeutic targets.
Authors and affiliations
Andrea Garcia-Perez ; Marta Duran-Renieblas ; Lucia Sanchez-Garcia; Jose L. Orgaz Universidad Carlos III de Madrid, Department of Neuroscience and Biomedical Sciences, Getafe, Spain. Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain
Abstract submission 32: Jenny Pui Ying Chan Wellcome Sanger Institute, Hinxton, United Kingdom
Combinatorial CRISPR screens and protein structure analysis to identify paralogue-selective synthetic lethal targets in melanoma
Abstract
Outcomes for patients with rarer melanoma subtypes remain poor. We recently performed combinatorial CRISPR-Cas9 screens across 10 uveal melanoma (UM) cell lines. Disruption of 514 gene pairs identified 105 high-confidence synthetic lethal (SL) interactions (Chan et al., Nature Genetics 2025), with the strongest signals enriched among paralogues. We aimed to identify paralogue-selective, structurally tractable sites to support therapeutic targeting across melanoma subtypes.
SL interactions were selected if significantly depleted in at least 6/10 screened cell lines. We mined our dataset to identify single-gene dependencies with paralogue partners, prioritising pairs in which one paralogue showed low expression using cell-line transcriptomics and/or Cell Model Passports. Paralogues were required to share ≥50% DNA sequence homology; genes with more than one paralogue were included if additional paralogues shared <20% homology. Extension across melanoma subtypes was assessed using DepMap/Project Score. Multiple sequence alignment and protein structure analysis were performed using Foldseek.
Paralogous genes accounted for 100% (23/23) of digenic SL interactions and 23% (19/81) of single-gene dependencies significantly depleted across at least 6 UM cell lines. Dependency negatively correlated with expression of the paralogue partner (low: log2(TPM+1) < 1; high: ≥ 1), most notably for CDS2 (P=6.18×10-33) and INTS6 (P=2.52×10-11), and extended to acral melanoma. CDS1/CDS2 (TM-score =0.868; RMSD=2.94Å) and INTS6/INTS6L (TM-score=0.608; RMSD=4.51Å) showed global structural similarity, but with discrete divergent regions that could be leveraged for paralogue-selective targeting. Notably, sequence divergence did not consistently co-localise with regions of local structural deviation.
SL paralogous genes are therapeutic targets in rare melanoma subtypes. Conventional CRISPR knockout approaches using binary gene disruption provide limited insight into which specific regions or resides of a protein drive SL. Nucleotide-resolution functional mapping is underway using genome editing to map tractable, functionally essential regions that are divergent from paralog partners, providing a blueprint for selective inhibitor design.
Authors and affiliations
Jenny Pui Ying Chan, Wellcome Sanger Institute, Hinxton, United Kingdom, Royal Marsden NHS Foundation Trust, London, United Kingdom; Diana Alexander, Wellcome Sanger Institute, Hinxton, United Kingdom; David Adams Wellcome Sanger Institute, Hinxton, United Kingdom
Session 4: precision immunotherapy
Abstract submission 37: Kieran Sefton, The University of Manchester, Manchester, United Kingdom
Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarisation in relapsed melanoma
Abstract
Despite the success of immune checkpoint blockade therapies targeting the PD-1/PD-L1 pathway for melanoma treatment, new therapeutics are necessary to overcome resistance. A key resistance driver is prolonged, ligand-independent interferon signalling, which ultimately leads to T cell exhaustion. A mono-ADP-ribosyl transferase that regulates chromatin accessibility, PARP14, has emerged as a mediator of resistance. We therefore assessed whether PARP14 inhibition (PARP14i) could restore effective anti-tumour immune responses to PD-1 blockade (αPD-1).
Pre-clinical models of acquired resistance following initial response to αPD-1 were applied to evaluate the effects of αPD-1 combined with PARP14i. Single-cell RNA sequencing (scRNA-seq) was employed to map T cell and macrophage states within the TME, with flow cytometry applied to validate phenotypic changes. These were linked to transcriptional signatures which predict clinical outcomes using Tumour Immune Dysfunction and Exclusion (TIDE) analysis.
Highly exhausted cytotoxic T cells with elevated interferon signalling were enriched in αPD-1-resistant tumours. Re-treatment with αPD-1 + PARP14i, however, diverted T cells from terminal exhaustion to delay tumour progression. scRNA-seq applied alongside TIDE analysis revealed a quiescent yet functional T cell state induced by this treatment, which is capable of reactivation, with a gene signature predictive of favourable outcomes. PARP14i also reshaped myeloid cells, promoting pro-inflammatory macrophages with elevated Pilra expression, a ligand implicated in generating CD8α-mediated T cell quiescence. These changes reinforced the quiescent T cell pool as reactivatable with enhanced anti-tumour response via Pilra macrophage modulation.
Combining αPD-1 with PARP14i represents a promising strategy to overcome ICBT resistance by diverting T cells from terminal exhaustion through maintaining a reactivatable pool. The identification of a CD8α–PILRA regulatory crosstalk between immune cell types highlights a previously unrecognised mechanism shaping T cell activity in the TME. These findings establish PARP14 as a key regulator of immune dysfunction and support its targeting as a next-generation immunotherapy approach for melanoma.
Authors and affiliations: Kieran Sefton; Rotem Leshem; I-Hsuan Lin; The University of Manchester, Manchester, United Kingdom Chun Wai Wong, The University of Manchester, Manchester, United Kingdom, Broad Institute, Cambridge, United States; Dervla Isaac, Mario Niepel, Ribon Therapeutics, Cambridge, United States Adam Hurlstone The University of Manchester, Manchester, United Kingdom
Abstract submission 15: Timothy Budden, University of Liverpool, Liverpool, United Kingdom
Spatial transcriptional biomarkers of outcome in primary cutaneous melanoma
Background
Outcomes in primary cutaneous melanoma vary considerably even among patients with similar clinicopathological features, highlighting the need for biomarkers that capture tumour–microenvironment (TME) interactions at diagnosis. We previously demonstrated that chronic UV-induced dermal remodelling diminishes melanoma invasion and impacts patient outcome, indicating that melanomas arising on chronically sun-damaged (CSD) skin may have fundamentally different tumour–microenvironmental biology compared with melanomas on sun-protected skin (non-CSD) melanomas. While prior bulk transcriptomic studies have established the prognostic relevance of immune and stromal states, the spatial organisation of these features across the tumour and surrounding tissue is not well understood and may reveal further prognostic markers in the tumour and the TME.
Methods
We applied spatial transcriptomics (Visium, 10x Genomics) on a panel of primary melanoma samples (pT1-pT4) to investigate how microenvironmental signatures across the tumour core, invasive front, and adjacent skin relate to patient survival and sun damage (CSD) status. To identify region specific clusters and signatures, we performed a region-wise integrative analysis across samples. To characterise the fibroblast landscape of each region, we additionally perform cell-type deconvolution using publicly available fibroblast atlases.
Results
We identified region-specific transcriptional differences across tumour, invasive front, and adjacent skin. Melanomas showed significant inter-sample heterogeneity, highlighting the challenge of designing robust prognostic biomarkers. However, transcriptionally distinct programs common across patients with shared clinical characteristics were identified. This revealed immune, metabolic and stromal/ECM-associated signatures were differentially expressed in patients who died, independently of primary tumour thickness.
Conclusions
Spatial transcriptomics provides a framework for characterising tumour and microenvironmental organisation in primary melanoma. By integrating spatial signatures with clinical data, this study identifies spatial features within and around primary tumours that could improve prognostication of melanoma.
Authors and affiliation
Timothy Budden, University of Liverpool, Liverpool, United Kingdom; Sokratia Georgaka The University of Manchester, Manchester, United Kingdom; Luisa Motta, Salford Royal Hospital, Manchester, United Kingdom, Amaya Viros Cancer Research UK Manchester Institute, Manchester, United Kingdom
Session 6: clinical trials and real-world data
Abstract submission 4: Ann Tivey, CRUK National Biomarker Centre, Manchester, United Kingdom
Tracking tumour and immune changes in cfDNA to predict response in advanced melanoma patients treated with immune checkpoint inhibitors.
Background
Currently, there are no clinically available biomarkers to identify which patients with advanced melanoma will respond to immune-checkpoint inhibitors (ICIs). Analysis of circulating-tumour DNA enables tracking of tumour activity and cancer intrinsic changes during treatment through assessment of mutations, copy-number aberrations and methylation profiles. However, the majority of cell-free DNA (cfDNA) is derived from immune cells, which can also be analysed using methylation and hydroxymethylation. We hypothesised that characterisation of both tumour and immune cell-derived cfDNA could identify responders vs. non-responders to ICIs and provide biological insight into tumour and immune changes throughout therapy.
Methods
CfDNA was isolated from baseline and pre-cycle-2 (C2) plasma samples from 18 patients with advanced melanoma (9 responders, 9 non-responders as per iRECIST). Genomic DNA was isolated from melanoma cell-lines and FACS isolated immune-cell populations to develop a reference methylation atlas for cfDNA deconvolution. Libraries were prepared using the duet-evoC assay and sequenced to ~10x depth which enables evaluation of mutations, methylation and hydroxymethylation. Tumour-fraction was estimated using the copy-number-based ichorCNA (v.0.3.2). Differentially (hydroxy)methylated regions were identified using methylKit R package (v1.30.0). We performed cfDNA deconvolution using our atlas with MetDecode (v1.0).
Results
Differentially (hydroxy)methylated regions could discriminate ICI responders vs. non-responders in baseline and C2 samples. Gene ontology analysis of regions hypomethylated in non-responder vs. responder samples showed enrichment for olfactory receptor signalling and keratinisation, whilst regions hypomethylated in responder samples were enriched for the PD-1 pathway. cfDNA deconvolution identified a rise in myeloid-derived cfDNA at C2 compared to baseline in non-responders (megakaryocytes p=0.005, granulocytes p=0.018, monocytes p=0.048).
Conclusion
Using a methylation-based assay, we are able characterise the tumour and immune cfDNA phenotypes in samples from patients with melanoma treated with ICIs. Data from a larger cohort (n=51) will be presented where we aim to identify cfDNA features associated with response.
Authors and affiliations
Ann Tivey; Scott Waterfield; Alexandra Clipson; Steven Hill; Alexandru Chelu; Kendal Wilson; Simon Hood; Dominic Rothwell; Caroline Dive; Florent Mouliere; CRUK National Biomarker Centre, Manchester, United Kingdom; Paul Lorigan, Rebecca Lee University of Manchester, Manchester, United Kingdom, The Christie NHS Foundation Trust, Manchester, United Kingdom
Abstract submission 39: Sarah Danson University of Sheffield, Sheffield, United Kingdom
Delivering cancer vaccines in the UK: the Vaccine Innovation Pathway
Background and aims
Cancer vaccines hold the promise of transforming cancer care. The UK has capitalised on its COVID-19 mRNA-based vaccine leadership to launch the Vaccine Innovation Pathway (VIP). The VIP is a national Clinical Trials Delivery Accelerator for cancer vaccine and infectious disease research. The VIP involves a partnership between the National Institute for Health and Care Research (NIHR), NHS England, and pharmaceutical partners. Cancer vaccine trials in melanoma have been a priority in this initiative.
Methods
The VIP has created a UK Cancer Vaccine Research Forum, bringing together experts in this field. Trial set up has been streamlined, through strategies such as pharmacy education and utilising the NCVR (National Contract Value Review). Alternative recruitment strategies are being employed, especially using the NHS England Cancer Vaccine Launchpad (CVLP), which identifies patients from numerous sites, improving equity of access, who can then be referred to treatment centres.
Results
The VIP has enabled a 500% increase in patient recruitment to cancer vaccine trials over 2 years. From April 2023 to November 2025, 2082 patients were enrolled in 35 trials across 88 sites and 11 cancer types. The CVLP is pre-screening patients across 55 NHS sites. Examples of success include: the UK provided 35% of the global recruitment to date for an ongoing study; the UK recruited the first patient, outside of the USA, to 5 studies; and the UK enrolled the first patient globally to 1 study. Updated results will be presented in March 2026.
Conclusions
The VIP has solidified the UK’s reputation at the forefront of the cancer vaccine research revolution. Trials have followed this success with more studies coming to the UK with additional patient cohorts as well as an increased number of trial sites. Improvements in clinical deployment are scalable beyond cancer vaccines and across disciplines.
Authors and affiliations
Sarah Danson University of Sheffield, Sheffield, United Kingdom, NIHR, London, United Kingdom; Robert Jones, University of Liverpool, Liverpool, United Kingdom, NIHR, London, United Kingdom; Kristina Duggleby; Joanna Calvert; Maria Koufali, NIHR, London, United Kingdom
Abstract submission 6: Kelly L Bowlt Blacklock, University of Edinburgh, Edinburgh, United Kingdom
Harnessing tigilanol tiglate for local control of canine oral mucosal melanoma: a translational approach to rare human melanomas
Background and aims
Canine oral mucosal melanoma (OMM) is an aggressive malignancy that closely parallels human mucosal melanoma at clinical, histopathological, and molecular levels. Cross-species transcriptomic work, including our recent analyses, has shown that human and canine mucosal melanomas segregate into conserved isubtypes, underscoring the strong translational relevance of the canine model. Surgery is the standard of care for local disease control in both species; however, major maxillofacial resections carry substantial morbidity. Tigilanol tiglate (TT), a novel intratumoural agent that induces rapid local tumour destruction, may offer a minimally invasive alternative. This study presents preliminary clinical data evaluating TT specifically for primary canine OMM.
Methods
All procedures were conducted under a UK Home Office licence (PP3782571) or the Veterinary Surgeons Act 1966.
Dogs with naturally occurring primary OMM were prospectively enrolled. Full body CT scans were performed. Tumours were staged and measured volumetrically before administration of intratumoural TT. Dogs were monitored for tumour response, necrosis dynamics, adverse events, and wound healing. The primary endpoints were complete local response and safety. For translational comparison, anonymised pre-treatment imaging of each case was independently reviewed by a blinded specialist veterinary surgeon, who planned a conventional surgical resection.
Results
To date, 2 dogs have been treated. TT induced rapid, predictable tumour destruction, resulting in complete local responses in both patients. All wounds resolved within 28 days. Adverse events were mild and self-limiting. Blinded surgical review indicated that both patients would have required major surgery associated with significant morbidity, whereas TT avoided the need for oral/maxillofacial resection. Circulating tumour DNA served as an orthogonal biomarker of tumour activity.
Conclusions
These preliminary results position TT as an effective local therapy for canine OMM and underscore its translational relevance, providing a comparative system capable of de-risking and accelerating the development of treatments for human mucosal melanoma.
Authors and affiliations
Kelly L Bowlt Blacklock, E. Elizabeth Patton University of Edinburgh, Edinburgh, United Kingdom
Abstract submission 13: Joe Thornton, Department of Clinical Development, Scancell Ltd, Oxford, United Kingdom
SCOPE: A phase 2 clinical trial evaluating an off-the-shelf DNA plasmid vaccine in first line advanced melanoma combined with checkpoint blockade – interim read-out
Background
SCIB1 & iSCIB1+ are DNA plasmid off-the-shelf vaccines encoding TRP-2 and gp100 and are HLA-Class I restricted. SCIB1 is restricted to HLA-A2, whereas iSCIB1+, includes additional epitopes enabling coverage across a broader set of HLA haplotypes (A2, A3, A31, Bw4, B35 & B44) representing approximately 80% of the population. When administered by needle-free injection, these are taken up by Antigen Presenting Cells, which directly present epitopes to CD-8 killer cells to generate an anti-tumour and memory immune response.
Methods
This phase 2 open label single arm multi-cohort clinical program evaluates the immune response, safety and efficacy of SCIB1 / iSCIB1+ administered alongside standard of care (SOC) checkpoint Inhibitors (CPI) in 130 advanced first line melanoma patients at 16 clinical sites in the United Kingdom since September 2022.
Expected results
OS, PFS, ORR and DCR determined by RECIST 1.1 and vaccine-induced T-Cell immunogenicity will be reported for HLA eligible patients vaccinated with SCIB1 and iSCIB1+ ( intra-muscular and intra-dermal administration) in combination with Ipilimumab + Nivolumab (I/N) and in patients receiving SCIB1 in combination with Pembrolizumab. These efficacy endpoints will be contextualised against known SOC CPI benchmarks and compared with results from HLA-mismatched participants. Safety analyses will include SUSARs, SAEs, ≥Grade 3 AEs and immune-mediated events across the full population.
Expected conclusions
This read-out is expected to demonstrate a clinical benefit from the addition of SCIB1 and iSCIB1+ to SOC CPIs. Furthermore, it is expected that the well tolerated safety profile of SCIB1 and iSCIB1+ will be confirmed. This data has determined the follow-on Phase III placebo-controlled and blinded registrational study, which has the potential to redefine the treatment of advanced unresectable melanoma, and this will be shared.
Authors and affiliations
Joe Thornton, Nermeen Varawalla, Olivia Howard, Robert Miller, Georgia Goodhew, Department of Clinical Development, Scancell Ltd, Oxford, United Kingdom; Lindy Durrant, Sam Paston Translational Research, Scancell Ltd, Oxford, United Kingdom; Heather Shaw, University College London Hospitals NHS Foundation Trust, London, United Kingdom; Philippa Corrie, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; Sarah Danson, Oncology and Metabolism Department, Weston Park Hospital – Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom; Miranda Payne, Oncology Dept., Churchill Hospital, Oxford, United Kingdom; Kate Young, Renal / Melanoma Department, The Royal Marsden Hospital – Chelsea, London, United Kingdom; Poulam Patel, Clinical Oncology, Nottingham Hospitals University Trust, Nottingham, United Kingdom; Maria Marples, Oncology, Leeds Cancer Centre, Leeds, United Kingdom; Ioannis Karydis, Cancer Care Department, Southampton General Hospital, Southampton, United Kingdom; Satish Kumar, Medical Oncology, Velindre Cancer Centre – Velindre NHS University Trust – NHS Wales, Cardiff, United Kingdom; Rebecca Lee, Medical oncology department, The University of Manchester, Manchester, United Kingdom; Claire Barlow, Oncology Dept., Musgrove Park Hospital – Taunton and Somerset NHS Foundation Trust, Taunton, United Kingdom; Kellati Prasad, Ruth Board, Medical Oncology, Royal Preston Hospital, Preston, United Kingdom; Martin Highley, Oncology Dept., Derriford Hospital Plymouth Hospitals NHS Trust, Plymouth, United Kingdom; Amna Sheri, Royal Free London NHS Foundation Trust, London, United Kingdom; Amanda Fitzpatrick, Guys and St.Thomas, London, United Kingdom
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