Combination of Plinabulin and Docetaxel More Effective Than Docetaxel Alone in Certain Patients With NSCLC

The combination of plinabulin and docetaxel increased overall survival (OS) in patients with second- and third-line non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) wild type compared to docetaxel alone, according to topline data from the DUBLIN-3 registrational trial. Plinabulin is a selective immunomodulating microtubule-binding agent (SIMBA), which is an antigen presenting cell (APC) inducer. According to the data, the combination also significantly improved overall response rate, progression-free survival, and 24- and 36-month OS rates, as well as a significant reduction in the incidence of grade 4 neutropenia.

“The treatment of second- and third-line NSCLC, especially with EGFR wild type where tyrosine kinase inhibitors do not work, is an area of severe unmet medical needs,” said Trevor M. Feinstein, MD, in a press release. “Now that checkpoint inhibitor immunotherapy has moved into first line, there is a vacuum in this indication, where treatment is heavily centered around docetaxel. Currently, docetaxel-based therapies have limited survival benefit and >40% severe neutropenia. In DUBLIN-3, a prolonged survival benefit, characterized by a long-tailed OS curve, was observed with plinabulin that represents an immune associated anti-cancer benefit. The opportunity that plinabulin offers to these patients is not only to live longer, but also with significantly reduced severe neutropenia, which are both meaningful for these very sick patients.”

The DUBLIN-3 phase 3 trial is a randomized, single blind to patients, active controlled, global trial that enrolled 559 patients with second- and third-line NSCLC and EGFR wild type with measurable lung lesions. Patients were either treated on a 21-day cycle with an infusion of docetaxel (75 mg/m2 on day 1) and plinabulin (30 mg/m2 on days 1 and 8) or docetaxel alone (75 mg/m2, day 1).

“The success of the DUBLIN-3 study represents proof-of-concept of plinabulin’s immune-enhancing mechanism of action that is complimentary to that of checkpoint inhibitors, and which is the rationale for it to be combined as triple IO combinations in multiple tumor indications,” said Ramon Mohanlal, MD, PhD, MBA, in the release. “These programs are already in phase 1/2 stage and preliminary positive results were reported at ASCO 2021.”

Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to 2 separate effects. First is a durable anticancer benefit because of the maturation of dendritic cells resulting in the activation of tumor antigen-specific T cells to target cancer cells, and second is an early onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells.

REFERENCE

BeyondSpring announces positive topline results from its DUBLIN-3 registrational trial of plinabulin in combination with docetaxel for the treatment of 2nd/3rd line non-small cell lung cancer (NSCLC) with EGFR wild type [news release]. Globe Newswire; August 4, 2021. Accessed August 5, 2021.