Addition of Plinabulin to Docetaxel Produced Positive Outcomes in Second- and Third-Line EGFR Wild-Type NSCLC

Combination plinabulin (BPI-2358) and docetaxel yielded a significant improvement in survival over docetaxel alone in the second- and third-line settings for patients with EGFR wild-type non–small cell lung cancer (NSCLC), according to a press release from drug developer BeyondSpring on the topline results of the phase 3 DUBLIN-3 trial (NCT02504489).¹

Findings from the study indicated that docetaxel plus plinabulin met the key primary end point of increased overall survival (OS; P = .03; log-rank P <.04), as well as the key secondary end points of significantly improved overall response rate (P <.03) and progression-free survival (P <.01). The combination was also found to decrease the incidence of grade 4 neutropenia (5.3%) over docetaxel alone (27.8%; P <.0001).

Moreover, docetaxel and plinabulin elicited a 24-month OS rate of 22.1% vs 12.5% in the docetaxel-alone arm (P <.01). Additionally, the 36-month OS rates in both arms were 11.7% and 5.3%, respectively (P = .04), and corresponding 48-month rates were 10.6% and 0%.

“DUBLIN-3 is a pivotal study which succeeded in demonstrating OS benefit for the first agent with a novel mechanism–plinabulin–since the 2015 nivolumab approval,” Yan Sun, MD, co-founder and former chairman of Chinese Society of Clinical Oncology (CSCO), chairman of NCCN Guidelines of NSCLC in China, and director of the Good Clinical Practice Center at the Cancer Hospital of Chinese Academy of Medical Sciences, said in a press release. “It was very rewarding to be the global Principal Investigator throughout the 6 years for the DUBLIN-3 trial that serves to address this severe unmet medical need. In the DUBLIN-3 study, it is especially gratifying to see the doubling of 24- and 36-month OS rate with a favorable safety profile in the plinabulin combination arm; this profile not only significantly advances NSCLC patients’ care, but also signals plinabulin’s profound immune anti-cancer benefit. The success of the DUBLIN-3 study is the gateway of plinabulin into multiple tumor indications within IO combinations.”

The registrational trial which assessed the efficacy of plinabulin—a first-in-class selective immunomodulating microtubule-binding agent that is a potent antigen-presenting cell inducer—in combination with docetaxel in the second- and third-line treatment of patients with EGFR wild-type disease enrolled 559 patients. The randomized, single-blinded, active-controlled global trial administered an infusion of docetaxel at a dose of 75 mg/m2 on the first day of a 21-day cycle at. Those who were assigned to the experimental arm also received a 30 mg/m2 dose of plinabulin on days 1 and 8.

In terms of safety, no unexpected adverse effects (AEs) were associated with the experimental regimen. A lower frequency of grade 4 AEs as well as a shift to lower-grade AEs was noted by investigators.

Plinabulin has previously demonstrated a promising protective benefit against chemotherapy-induced neutropenia in patients with NSCLC, with a phase 2 clinical trial indicating that a single dose-per-cycle of the agent demonstrated a similar benefit to pegfilgrastim (Neulasta).² As investigators escalated the dose of plinabulin, the overall incidence of neutropenia decreased. There were no notable differences in mean days of severe neutropenia noted among those who received pegfilgrastim on day 2 vs day 1 (20 mg/m2) with plinabulin

“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 [immunotherapy] combinations in multiple tumor indications. These programs are already in phase 1/2 stage and preliminary positive results were reported at [the 2021 American Society of Clinical Oncology Annual Meeting],” Ramon Mohanlal, chief medical officer and executive vice president of research and development at BeyondSpring, concluded.3

References

1. BeyondSpring Announces Positive Topline Results from its DUBLIN-3 Registrational Trial of Plinabulin in bomcination with Docetaxel for the treatment of 2nd/3rd line non-small cell lung cancer (NSCLC) with EGFR wild type. News release. BeyondSpring. August 4, 2021. Accessed August 4, 2021. https://bit.ly/3inGCfV
2. Blayney DW, Zhang, Q, Feng J, et al. Efficacy of plinabulin vs pegfilgrastim for prevention of chemotherapy-induced neutropenia in adults with non-small cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol. 2020;6(11):e204429. doi:10.1001/jamaoncol.2020.4429
3. Malhotra J, Hanna NH, Chiappori A, et al. A phase I trial of plinabulin in combination with nivolumab and ipilimumab in patients with relapsed small cell lung cancer (SCLC): Big Ten Cancer Research Consortium (BTCRC-LUN17-127) study. J Clin Oncol. 2021; 39(suppl 15):8570. doi:10.1200/JCO.2021.39.15_suppl.8570