Kimmtrak (tebentafusp-tebn) / Immunocore, Medison - LARVOL DELTA

Circulating tumor DNA is prognostic of patient outcome and enables therapy monitoring in metastatic uveal melanoma. (PubMed, Clin Cancer Res) - "Both the presence and level of ctDNA at baseline, along with persistence of ctDNA within 3months of treatment-start, are strong negative prognostic markers in mUM. These findings support the clinical utility of ctDNA as a non-invasive tool for disease monitoring."

Circulating tumor DNA • Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • GNAQ

Phase 2 Combination of Melphalan/HDS Via PHP + Tebentafusp in Treating Metastatic Uveal Melanoma (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute

New P2 trial • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Bispecific immunotherapy based on antibodies, T-cell receptors, and aptamers: mechanisms of action, adverse effects, and future perspectives. (PubMed, Front Immunol) - "IgG formats-including blinatumomab, teclistamab, mosunetuzumab, and tarlatamab-achieve high objective-response rates in hematologic malignancies and are increasingly demonstrating clinical activity in solid tumors. TCR-based constructs broaden the repertoire of actionable targets by recognizing intracellular antigens presented on MHC molecules, as exemplified by the approval of tebentafusp for uveal melanoma...The integrated evidence indicates that continued progress in bispecific immunotherapy will depend on the incorporation of predictive molecular biomarkers, dynamic monitoring of the evolving antigenic landscape, and the standardization of biomanufacturing processes. These advances are expected to accelerate the clinical deployment of next-generation, multipurpose bispecific constructs."

Adverse events • IO biomarker • Journal • Review • Eye Cancer • Fibrosis • Hematological Disorders • Hematological Malignancies • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Montelukast as a novel therapeutic approach in metastatic uveal melanoma harboring a CYSLTR2 mutation: a translational case report. (PubMed, ESMO Open) - "This is the first published case suggesting a potential role for leukotriene receptor antagonists in CYSLTR2-mutant UM. These findings support further preclinical and clinical investigation of montelukast as a repurposed therapy in this challenging disease entity."

IO biomarker • Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CYSLTR2

Real-world study on tebentafusp use in metastatic uveal melanoma in France: Interim analysis of the PRIMUM.0 study (ESMO-IO 2025) - "The median and 1-yr OS was 29 [21-not-reached] months and 85% [76–91%] in first-line patients and 19 [16- 22] months and 75% [56-87%] in 2L+ patients. The safety profile was consistent with known data, with no unexpected safety signals.Conclusions This real-world analysis provides compelling evidence supporting the survival benefit and safety profile of tebentafusp observed in the pivotal phase 3 study, affirming its use as a first-line standard of care for HLA-A*02:01-positive patients with mUM.Legal entity responsible for the study Immunocore."

Clinical • Metastases • Real-world • Real-world evidence • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A

Tebentafusp in Metastatic Uveal Melanoma: A Meta-analysis. (PubMed, Target Oncol) - "Tebentafusp for patients with HLA-A*02:01-positive mUM is associated with improved survival outcomes and manageable toxicity. These findings support tebentafusp as the standard of care for this patient population."

Journal • Retrospective data • Review • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A

Tebentafusp-tebn With LDT in Metastatic UM (clinicaltrials.gov) - P1/2 | N=109 | Recruiting | Sponsor: Thomas Jefferson University | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2032 ➔ Aug 2032 | Trial primary completion date: May 2030 ➔ Oct 2030

Enrollment open • Trial completion date • Trial primary completion date • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Dermatological Toxicities of Tebentafusp, a New Bispecific Drug: Case Series and Literature Review. (PubMed, Australas J Dermatol) - "Dermatological involvement is common and manageable, highlighting the need for early dermatological input in patients receiving tebentafusp. Emerging data suggest a possible association between rash and response, which warrants further investigation."

Journal • Dermatology • Eye Cancer • Immunology • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • Vitiligo • CD8 • HLA-A

Real-World Outcomes of Ipilimumab-Nivolumab vs. Anti-PD-1 Monotherapy in Metastatic Uveal Melanoma: A Single-Center Retrospective Study. (PubMed, Cancers (Basel)) - "Anti-PD-1 monotherapy demonstrated limited clinical activity, providing little benefit beyond conventional chemotherapy. Dual checkpoint blockade with ipilimumab and nivolumab achieved higher response and disease control rates, albeit with increased toxicity, suggesting a potential benefit for selected patients. Tebentafusp has emerged as an effective option and a new standard of care for a molecularly defined subgroup of HLA-A*02:01-positive patients. However, for the majority of individuals with metastatic uveal melanoma, effective systemic therapies remain an unmet need."

Journal • Monotherapy • Real-world evidence • Retrospective data • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A

Characterization of long-term survivors with liver metastases from uveal melanoma diagnosed between 2005 and 2021. (PubMed, Int J Cancer) - "Notably, all patients with chemosaturation as their first liver-specific procedure achieved DC. Further data are needed on the combination of liver-directed therapy and ST, such as ICI or Tebentafusp."

Journal • Cutaneous Melanoma • Eye Cancer • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

KIMMTRAK (GlobeNewswire) - "KIMMTRAK net product sales were $103.7 million and $295.5 million for the three and nine months ended September 30, 2025, respectively, representing increases of 29% and 31% respectively, as compared to the same periods in 2024....The Company is currently enrolling patients in the TEBE-AM registrational Phase 3 trial and expects to complete enrollment in the first half of 2026."

Enrollment status • Sales • Cutaneous Melanoma • Uveal Melanoma

Tebentafusp in mUM – mechanism of action and therapy management (DGHO 2025) - "Sponsored by Immunocore."

Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Reactivation of Tebentafusp-Induced Skin Toxicity Following PRAME-Specific TCR-T Cell Therapy in Uveal Melanoma (DGHO 2025) - "We report a case of reactivated skin toxicity following PRAME-specific TCR-T therapy in a uveal melanoma patient previously treated with Tebentafusp.A 65-year-old male with metastatic uveal melanoma, refractory to multiple treatments including Tebentafusp, received an IMA203 TCR-T-cell product within compassionate use. This case highlights the importance of considering prior immune-related toxicities when managing solid tumor patients undergoing cellular therapies. Ongoing deep immunophenotyping of peripheral blood via spectral flow cytometry will be presented to further elucidate immune dynamics underlying both therapeutic response and immune-mediated toxicity"

IO biomarker • Dermatology • Eye Cancer • Immunology • Melanoma • Pruritus • Solid Tumor • Uveal Melanoma • PRAME

Phase 2 Trial of TIL Therapy for Metastatic Uveal Melanoma: Evaluating Cellular Potency and Tumor Transcriptomic Predictors of Response (SITC 2025) - P2 | "Patients received non-myeloablative lymphodepletion with cyclophosphamide and fludarabine, followed by infusion of TIL and high-dose interleukin-2...The median number of prior metastatic therapies was two, including checkpoint blockade in 61% and tebentafusp in 32% of patients...Integration of transcriptomic biomarkers such as UMIS to identify metastases harboring potent TIL may optimize patient selection and improve outcomes.Acknowledgements Aldesleukin was provided by Clinigen Limited and Iovance Biotherapeutics.Trial Registration NCT03467516Ethics Approval Patients gave informed consent prior to trial participation in accordance with the Declaration of Helsinki. This trial was reviewed and approved by the University of Pittsburgh Institutional Review Board (Approval CR19110103-018).Abstract 598 Figure 1Request permissionsWaterfall plot of clinical responses in patients with metastatic uveal melanoma after TIL therapy (NCT03467516">NCT03467516)Abstract 598..."

Metastases • P2 data • Eye Cancer • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD8

Discovery and validation of DARKFOXTM, a novel alternative open reading frame of FOXM1 that is an attractive cancer antigen for peptide-HLA targeting immunotherapy (SITC 2025) - "Background Targeted immunotherapies are a highly promising treatment strategy for solid tumors, exemplified by the recent FDA approvals of tebentafusp and afamitresgene autoleucel, which target Class I peptide-HLA (pHLA) antigens...It is characterised by minimal presence in normal tissues, homogeneous intratumoral expression, and robust presentation by HLA on the surface of tumor cells. ENA101, an EnTiCE® bispecific T-cell engager targeting DARKFOX-A3, is currently in IND-enabling studies."

IO biomarker • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOXM1

A novel bispecific T cell engager for the treatment of solid tumors that express DARKFOXTM, a previously undiscovered antigen derived from an alternative open reading frame of FOXM1 (SITC 2025) - "Background Bispecific T cell engagers (TCEs) have demonstrated significant clinical benefit in solid tumors as evidenced by the approvals of tebentafusp and tarlatamab. These TCEs exhibit robust and selective redirection of T cell activity toward DARKFOX-expressing cells across multiple tumor types. Affinity-enhanced binders derived from these sequences will be selected to advance into IND-enabling studies with Enara's EnTiCE® half-life-extended TCE platform."

Oncology • Ovarian Cancer • Solid Tumor • FOXM1

Novel anti-CD3 heavy chain-only antibodies for use in T-cell engaging immunotherapeutics (SITC 2025) - "As TCE bispecific molecules, the panel displayed a promising functional potency range; with two molecules displaying comparable in vitro tumor cell killing efficacy to clinically validated molecules such as tebentafusp.Conclusions In this work, we showcase the discovery and engineering of novel anti-CD3 HCAbs, which demonstrate T cell cytotoxicity comparable to clinically validated TCEs when paired with IgG or TCR modalities. This introduces a flexible new tool for advancing the TCE class of biologics."

Oncology

VIB193, the first TCE prodrug targeting CAIX for the treatment of solid cancer (SITC 2025) - "Background The approval of Catumaxomab, the first T cell engager (TCE) for solid tumors in 2009 brought hope that TCEs could achieve both high response rates and durable benefits in solid tumor patients. However, over the following 15 years, efforts to develop TCEs for solid tumors have led to the approval of only two additional drugs: the TCR-based Tebentafusp and the antibody-based Tarlatamab...These rendered VIB193 a high therapeutic window not observed with conventional TCEs. It is noteworthy that, due to high TCE's high potency, VIB193 was able to achieve complete responses (per mRECIST criteria) at low doses.Conclusions VIB193 holds promise for the treatment of a wide range of solid tumors and represents a significant step forward toward overcoming the challenges traditionally associated with TCEs for solid tumors.Ethics Approval Ethical committee approval ID number for the animal work 20250206C02, Guangzhou, China."

Lung Cancer • Oncology • Solid Tumor • CA9

Evaluating the prognostic impact of tebentafusp-associated cutaneous toxicities on survival in 83 uveal melanoma patients: a multi-institutional cohort study (SITC 2025) - "These results suggest that tebentafusp-associated cAEs may serve as an early clinical marker of therapeutic efficacy. Future studies are warranted to elucidate the underlying mechanisms driving this relationship.Ethics Approval The study was approved by the Mass General Brigham Institutional Review Board (Protocol #2022P002518).Consent The study meets the criteria of secondary research, for which patient consent was not required.Abstract 1039 Table 1View inline•Open as popupBaseline characteristics of metastatic uveal melanoma patients treated with tebentafuspAbstract 1039 Table 2View inline•Open as popupOverall survival among metastatic uveal melanoma patients treated with tebentafusp"

Clinical • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A

Tebentafusp controls disease and prolongs survival by increasing the T cell:tumor cell ratio, activating T cells and inhibiting tumor proliferation in metastatic uveal melanoma patients (SITC 2025) - P1/2 | "Med. 2022; 28:2364–2373.Abstract 959 Table 1View inline•Open as popupMean fold changes of T cell counts and gene signatures in patient biopsies from tebentafusp-treated mUM patients"

Clinical • IO biomarker • Metastases • Tumor cell • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CASP3 • CASP7 • CD28 • CTLA4 • GPR183 • HLA-A • LAG3 • PD-L1 • PD-L2 • PRAME

Cancer Vaccination Induces High-Avidity T Cell Receptors Reactive to Endogenously Presented Target Antigens for Use in Future T Cell Therapies for HLA-A*03:01+ Cancer Patients (SITC 2025) - P1 | "Background FDA-approved therapies afamicel and tebentafusp target peptide antigens from MAGE-A4 and gp100, presented by HLA-A*02:01. Engineered primary CD8+ T cell expression of activation-induced markers (C) and specific lysis at varying E:T ratios (D)Abstract 340 Figure 2Request permissionsReactivity of a TCR targeting MAGE-A196-104 from patient VMM1113. Expression of activation-induced markers (A), secretion of IFNγ (B) and TNFα (C), and specific lysis at varying E:T ratios (D) by engineered primary CD8+ T cells after coculture with human cancer cell lines"

Clinical • IO biomarker • Melanoma • Oncology • Solid Tumor • CD69 • CD8 • HLA-A • IFNG • IL2RA • MAGEA4 • TNFA • TNFRSF9

Phase 2 trial of TIL therapy for metastatic uveal melanoma: Evaluating cellular potency and tumor transcriptomic predictors of response (SITC 2025) - P2 | "Patients received non-myeloablative lymphodepletion with cyclophosphamide and fludarabine, followed by infusion of TIL and high-dose interleukin-2...The median number of prior metastatic therapies was two, including checkpoint blockade in 61% and tebentafusp in 32% of patients...Integration of transcriptomic biomarkers such as UMIS to identify metastases harboring potent TIL may optimize patient selection and improve outcomes.Acknowledgements Aldesleukin was provided by Clinigen Limited and Iovance Biotherapeutics.Trial Registration NCT03467516Ethics Approval Patients gave informed consent prior to trial participation in accordance with the Declaration of Helsinki. This trial was reviewed and approved by the University of Pittsburgh Institutional Review Board (Approval CR19110103-018).Abstract 598 Figure 1Request permissionsWaterfall plot of clinical responses in patients with metastatic uveal melanoma after TIL therapy (NCT03467516">NCT03467516)Abstract 598..."

Metastases • P2 data • Eye Cancer • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD8

Discovery and validation of DARKFOXTM, a novel alternative open reading frame of FOXM1 that is an attractive cancer antigen for peptide-HLA targeting immunotherapy (SITC 2025) - "Background Targeted immunotherapies are a highly promising treatment strategy for solid tumors, exemplified by the recent FDA approvals of tebentafusp and afamitresgene autoleucel, which target Class I peptide-HLA (pHLA) antigens...It is characterised by minimal presence in normal tissues, homogeneous intratumoral expression, and robust presentation by HLA on the surface of tumor cells. ENA101, an EnTiCE® bispecific T-cell engager targeting DARKFOX-A3, is currently in IND-enabling studies."

IO biomarker • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOXM1

PLUME: A single-arm phase II trial of pembrolizumab (pembro) plus lenvatinib (lenva) in patients (pts) with metastatic uveal melanoma (mUM) (ESMO 2025) - P2 | "Clinical trial identification NCT05282901. Table: LBA58 Cohort 1 Tebentafusp-naive HLA A*02-01neg n=22 assessable pts Cohort 2 Tebentafusp-pretreated HLA A*02-01pos n=29 assessable pts Predefined statistical threshold for success ≤16 ≤17 Observed progressions at 27 weeks 15 11 % PFS at 27 weeks [IC95%] 31.8% [13.9 - 54.9] 60.7% [40.6 - 78.5] Conclusions Pembro+lenva met the predefined 27-week PFS success criteria in both Tebe-naïve and Tebe-pretreated cohorts, with particularly encouraging activity in Tebe-pretreated patients. Biomarker and real-world comparisons are ongoing."

Clinical • IO biomarker • Late-breaking abstract • Metastases • P2 data • Eye Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor • Uveal Melanoma

Evaluating the efficacy and safety of tebentafusp in the treatment of metastatic uveal melanoma: a 2025 update systematic review and meta-analysis. (PubMed, Front Oncol) - "Additionally, circulating tumor DNA (ctDNA) may serve as a more sensitive efficacy biomarker than radiological responses, warranting further investigation. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251084090."

IO biomarker • Journal • Retrospective data • Review • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A