Dual immunotherapy plus lenvatinib shows early promise in endometrial cancer

Women with advanced endometrial cancer that has progressed after platinum-based chemotherapy have few good options. One established second-line combination pairs an immune-checkpoint inhibitor with lenvatinib, a drug that starves tumours of blood supply. A small trial published on 4 September in Nature Communications tests a variation on that theme, swapping in a newer, two-in-one antibody [s1].

What the trial tested

The CLEAR-EC trial was a single-arm, multicentre phase II study with a safety run-in [s1]. It combined lenvatinib with cadonilimab — a bispecific antibody that blocks two immune checkpoints at once, PD-1 and CTLA-4 — as second-line or later treatment [s1]. Three patients were enrolled in the safety run-in, followed by 29 more once the recommended dose was set, and no dose-limiting toxicities occurred, establishing lenvatinib 16 mg once daily plus cadonilimab 10 mg/kg every three weeks as the phase II dose [s1]. The primary endpoint was objective response rate — the share of patients whose tumours shrank by a defined amount [s1].

What it found

The trial met its primary endpoint, with an objective response rate of 40.6% (95% CI, 23.7–59.4) [s1]. The disease-control rate — responses plus stable disease — was 81.3% (95% CI, 63.6–92.8), and median progression-free survival was 13.8 months [s1]. Median overall survival had not been reached at the time of analysis, meaning more than half of participants were still alive, so that figure cannot yet be stated [s1]. On the safety side, grade 3 or higher treatment-related adverse events occurred in 40.6% of patients [s1]. An exploratory analysis found that early on-treatment levels of circulating tumour DNA — fragments of cancer DNA in the blood — were associated with both progression-free and overall survival [s1].

How much weight it can bear

These are encouraging numbers for a hard-to-treat cancer, but the design demands restraint. This was a single-arm trial of roughly 32 patients, with no control group [s1]. Without randomised comparison, there is no way to know how these results stack up against the existing checkpoint-inhibitor-plus- lenvatinib regimens, or against lenvatinib alone — a response rate that looks strong in isolation can shrink or vanish against an active comparator. The wide confidence interval around the response rate (23.7% to 59.4%) reflects how few patients were involved [s1].

The toxicity is not trivial either: with grade 3-or-higher treatment-related adverse events in more than four in ten patients, this is a demanding regimen, and the numbers here reflect drug doses and side effects that only a clinician can weigh for an individual [s1]. The circulating-tumour-DNA finding is explicitly exploratory — a hypothesis for future study, not a validated way to predict who will benefit [s1].

Why it matters

Bispecific antibodies like cadonilimab aim to deliver dual checkpoint blockade in a single molecule, potentially simplifying a combination that otherwise means two separate drugs. CLEAR-EC provides an early, single-arm signal that the approach is active in previously treated endometrial cancer and tolerable at the tested dose [s1]. Whether it improves on what is already available is a question only a randomised trial can answer, and this study does not attempt it.

This article is informational and does not constitute medical advice.

Sources

• [s1] Cadonilimab plus lenvatinib in advanced endometrial cancer: the multicenter, phase II CLEAR-EC trial. Nature Communications, 4 September 2026. https://doi.org/10.1038/s41467-026-77467-3