On December 11, 2024 EORTC and Immunocore reported the randomisation of the first patient in the Phase 3 Adjuvant Trial in Ocular Melanoma (ATOM), investigating the safety and efficacy of tebentafusp as adjuvant treatment for uveal melanoma (Press release, EORTC, DEC 11, 2024, View Source [SID1234649044]).

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The primary objective of the open-label, international, multicentre trial – led by EORTC – will be to assess whether tebentafusp can prevent or delay relapse in patients with primary ocular (uveal) melanoma at high risk of relapse, as compared with observation. Tebentafusp is approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in 38 countries, under the brand name KIMMTRAK.

"I am delighted that the first patient on ATOM has been recruited. This milestone reflects a very significant effort by the EORTC melanoma group trials team, colleagues at Immunocore and our trial sites," said Professor Paul Nathan, ATOM study coordinator. "The study addresses a key question – whether the benefit seen with tebentafusp in HLA-A*02:01-positive patients with metastatic uveal melanoma will translate to a significant reduction in risk of relapse for patients who have received treatment for primary uveal melanoma and are at high risk of relapse."

The trial is expected to enrol 290 HLA-A*02:01-positive patients with uveal melanoma who have undergone definitive treatment by surgery or radiotherapy. Eligible patients will be randomised 1:1 to one of two arms: tebentafusp [as monotherapy] for six months or until disease relapse, or observation. Secondary objectives include overall survival, safety and tolerability, while exploratory objectives include evaluation of circulating tumour DNA (ctDNA) as a marker of residual disease, and a comparison of health-related quality of life.

Mohammed Dar, Chief Medical Officer at Immunocore, said: "Despite definitive local therapy, approximately 50% of patients will eventually relapse with metastatic disease. The goal of investigating adjuvant tebentafusp following primary treatment is to prevent future recurrence. Decreasing the likelihood of a patient relapsing following definitive therapy for their primary disease would be a groundbreaking advancement in treatment, given there are currently no standard treatment options available in this setting."

About the ATOM Phase 3 trial
ATOM (NCT06246149; 2023-510333-28-00) is an EORTC-led randomised open-label international multicentre Phase 3 superiority clinical trial aiming to prospectively assess whether adjuvant treatment with tebentafusp improves relapse-free survival as compared with observation. A total of 290 patients are expected to be enrolled within a span of three years, beginning in 13 countries, and with the potential for further expansion.

The goal of the experimental treatment strategy in the trial is to establish whether adjuvant tebentafusp can decrease the risk of relapse – compared to observation – in patients who have undergone definitive treatment for primary uveal melanoma and who are at high risk of relapse.

Patients included in the study must have undergone definitive treatment for primary ocular melanoma, by surgery or radiotherapy; be at high risk of relapse; be HLA-A*02:01 positive; have a good performance status (ECOG 0/1); and adequate organ function. Eligible patients will be randomised 1:1 to receive either active treatment with weekly tebentafusp [as monotherapy], or observation. Patients will receive tebentafusp for 6 months, or until relapse.

The secondary objectives are to compare overall survival and to further document the safety and tolerability of tebentafusp.

The exploratory objectives include the comparison of the health-related quality of life between the treatment arms and the evaluation of the role of circulating tumour DNA (ctDNA) as a biomarker for the presence of residual disease.

About Uveal Melanoma
Uveal melanoma is a rare disease arising from the pigmented uveal tract of the eye with an estimated incidence in Europe of 4.4 cases per million [i]. Up to 50% of people with uveal melanoma will eventually develop metastatic disease [ii]. Metastases usually appear within a median of three to five years after treatment of primary tumours, and treatment of metastatic disease is usually with palliative intent. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

Very few studies have tested the use of adjuvant treatment in uveal melanoma, and none have resulted in any change in the standard of care, reflecting a lack of active agents for this disease.

[i] Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A, Crocetti E, et al. Incidence of Uveal Melanoma in Europe. Ophthalmology 2007.
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[ii] Shields CL, Furuta M, Thangappan A, Nagori S, Mashayekhi A, Lally DR, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol 2009.
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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 recognise 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 tumours, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumours, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumours.