Akeso looks early in small-cell lung cancer

Small-cell lung cancer, for years a disease with few options, is evolving – and Akeso is making a bid for a piece of the market with its Summit-partnered PD-1 x VEGF drug ivonescimab. A Chinese phase 3 trial, recently posted on clinicaltrials.gov, has just begun in limited-stage SCLC.

Ivonescimab will be given here as consolidation treatment in patients who haven’t progressed following concurrent chemotherapy. AstraZeneca’s checkpoint inhibitor Imfinzi was FDA approved in a similar setting last December, based on the Adriatic trial. And Amgen has a phase 3 trial under way of its DLL3-targeting T-cell engager Imdelltra as maintenance in limited-stage SCLC.

At the recent ASCO meeting, Amgen talked up the curative potential of Imdelltra here. However, it’s notable that both Akeso and Amgen’s trials are using placebo as a control, rather than Imfinzi. This might be acceptable in a Chinese study, but Amgen’s global trial could face questions from regulators – although it did start before Imfinzi was approved.

In Adriatic Imfinzi reduced the risk of death by 27% versus placebo, setting a benchmark for the other projects to hit.

Limited-stage SCLC is generally found in one lung or one side of the chest, and accounts for approximately 30% of SCLC diagnoses, according to AstraZeneca.

Others looking at this niche include GSK and Hansoh, with their B7-H3 ADC GSK5764227. However, Hansoh’s Chinese phase 3 Artemis-008 study is enrolling a different population: limited as well as extensive-stage patients who have relapsed on or after platinum-based chemo.

Extensive push

Amgen is also making a broader push with Imdelltra into first-line extensive-stage SCLC, a more advanced form of disease. Imdelltra already has accelerated approval in second-line extensive-stage SCLC, and this looks likely to be converted into full approval, based on results of the confirmatory Dellphi-304 trial presented at ASCO.

Akeso said back in 2022 that it planned to begin a phase 3 study of invonescimab in extensive-stage SCLC, but this trial hasn’t emerged. Still, the group has been busy, with pivotal study starts in other solid tumours, including pancreatic cancer.

Meanwhile, Summit’s focus with US trials seems to be squarely on NSCLC, at least for now. In second-line EGFR-mutant NSCLC the global Harmoni trial recently disappointed on overall survival.

Ivonescimab's phase 3 trials outside NSCLC

Notes: all are Akeso-sponsored Chinese trials; HNSCC=head and neck squamous cell carcinoma; TNBC=triple-negative breast cancer. Source: OncologyPipeline & clinicaltrials.gov.