ESMO21: BeyondSpring details data from pivotal lung cancer study of plinabulin combo

BeyondSpring Pharmaceuticals on Monday released detailed results from the Phase III DUBLIN-3 study, with the combination of plinabulin and docetaxel showing a significant improvement in overall survival (OS) versus docetaxel alone for the treatment of second- or third-line non-small-cell lung cancer (NSCLC) patients with EGFR wild type. The data were presented at the European Society for Medical Oncology (ESMO) congress.

The company announced in August that the trial achieved its main goal, with shares more than tripling on the news. However, the drugmaker's stock slipped as much as 33% on Monday.

Questions over survival benefit

Results showed that in the intention-to-treat population of 559 patients, mean OS was 15.1 months for plinabulin plus docetaxel, compared to 12.8 months for docetaxel alone, while median OS in the two treatment groups was 10.5 months and 9.4 months, respectively. The study also met key secondary endpoints, with plinabulin plus docetaxel showing significant improvements versus docetaxel alone on overall response rate and progression-free survival (PFS), as well as 24- and 36-month OS rates (see table below).

BeyondSpring noted that as DUBLIN-3 started in 2015, only 23% of patients in the trial had received prior treatment with a PD-(L)1 inhibitor, despite this now being a widely used first-line treatment. In this subgroup, results showed that mean OS in those given plinabulin plus docetaxel was 18.3 months, versus 14 months for docetaxel alone, while median OS in the two arms was 12.3 months and 12.1 months, respectively (see table below).

Lead investigator Trevor Feinstein noted that "with immunotherapies [having now] moved to first line, docetaxel-based therapies are the mainstay therapy" in second- and third-line NSCLC. However, he pointed out that docetaxel is "known to cause safety concerns such as >40% severe neutropenia." Results from DUBLIN-3 showed that the combination of plinabulin and docetaxel significantly reduced the incidence of Grade 4 neutropenia, with a rate of 5.3% versus 27.8% for docetaxel alone.

Maurice Pérol, who co-chaired a discussion of the results at ESMO, asked whether the benefit seen in the study was due to an antitumour effect or an improvement in docetaxel dose intensity, although data on this were not presented. Meanwhile, Feinstein suggested that the benefit observed in DUBLIN-3 was not due to an increase in response, but rather an increase in the durability of response – although data were not available to support this.

Filings planned for 1H 2022

Commenting on the possible utility of plinabulin, Pérol said that if approved, it may be used in frail patients where there are concerns about the haematological toxicity of docetaxel. BeyondSpring CEO Lan Huang noted that the company is "working to prepare the NDA submission package for this indication in both the US and China and [we] are planning to file these…in 1H 2022." Along with questions over the survival benefit seen in the study, concerns were also raised about the study population, which was predominantly made up of patients form China, and how this will be viewed by the FDA.

Plinabulin, a selective immunomodulating microtubule-binding agent (SIMBA), is currently under review in China and the US for use in combination with G-CSF for the prevention of chemotherapy-induced neutropenia, with a target review date of November 30 in the latter country.

Join FirstWord editors Michael Flanagan, Virginia Li and Simon King on Wednesday 22 September (3pm GMT / 10am EST) for a discussion on five key takeaways from the ESMO congress. Register for free here.

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