Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2026
Circulating Thymidine Kinase Activity Predicts Survival and Optimal Treatment Sequencing in BRAF-Mutated Metastatic Melanoma in the SECOMBIT Trial.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02631447 (A Three Arms Prospective, Randomized Phase II Study to Evaluate the Best Sequential Approach With Combo Immunotherapy), which is not on this map. Not yet cited in PubMed.
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A Three Arms Prospective, Randomized Phase II Study to Evaluate the Best Sequential Approach With Combo Immunotherapy (Ipilimumab/Nivolumab) and Combo Target Therapy (LGX818/MEK162) in Patients With Metastatic Melanoma and BRAF Mutation
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27 authors.
Funding
Abstract
purposeAlthough immune checkpoint inhibitors (ICI) are generally the preferred first-line treatment for metastatic BRAF V600-mutated melanoma, a subgroup that remains incompletely defined requires initial tumor control with BRAF/MEK-targeted therapy (TT). The purpose of this study was to evaluate circulating thymidine kinase activity (TKa), a blood-based marker of cellular proliferation, as a biomarker of outcome and treatment sequencing in patients enrolled in the randomized phase II SECOMBIT trial (NCT02631447). PATIENTS AND
methodsSerum TKa was analyzed in samples from patients at baseline and during treatment. Patients were stratified by median baseline TKa, and survival outcomes were compared across three strategies for first- and second-line treatments: TT followed by ICI (arm A), ICI followed by TT (arm B), and a "sandwich" strategy with short-term TT induction prior ICI (arm C) followed by TT.
resultsIn TKa-low (n = 41) versus TKa-high (n = 40) patients, the first progression-free survival (PFS) at 5 years was 43.3% versus 27.5% (P = 0.062), the total PFS was 60.8% versus 35% (P = 0.004), and overall survival (OS) was 70.7% versus 36.9% (P < 0.001), respectively. TKa-low patients had, compared with TKa-high, significantly longer total PFS and OS in arms A and B. Notably, TKa-high patients showed improved outcomes with the sandwich strategy compared with other sequences. Longitudinal analyses revealed an early TKa increase in the majority of patients receiving ICI and increasing TKa levels at disease progression.
conclusionsThese findings suggest that circulating TKa could serve as a clinically actionable biomarker for risk stratification, treatment sequencing, and on-treatment disease monitoring.
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