Talk:Plinabulin

Plinabulin (BPI-2358, NPI-2358) is an analogue of a marine microbial product developed by San Diego-based Nereus Pharmaceuticals. Global rights to plinabulin were acquired in 2013 by BeyondSpring Pharmaceuticals, a company based in New York, NY. BeyondSpring utilizes a novel scalable business model that integrates world-wide resources to accelerate the drug development of plinabulin through Phase 3 clinical trials. A major emphasis is placed on trials in China in addition to USA and EU. Plinabulin is being developed through clinical trials as an anticancer agent in patients with non-small cell lung cancer (NSCLC) and for the prevention of chemotherapy-induced-neutropenia (CIN). Active anti-cancer trials aim to demonstrate that plinabulin extends survival in advanced NSCLC patients, when combined with docetaxel. Ongoing CIN focused trials are designed to demonstrate prevention of neutropenia induced by docetaxel in NSCLC, prostate cancer and breast cancer patients, and by the combination of taxotere/adriamycin/cyclophosphamide in breast cancer patients. BeyondSpring has indicated regulatory filings for marketing approval of Plinabulin will be made in multiple countries in the coming years, including filings in China, USA and the European Union.

Mechanism of ActionPlinabulin binds to  tubulin at very low concentrations (low nanomolar) in a site near, but distinct from the colchicine binding site. This binding is thought to underlie the biological effects of plinabulin, including collapse of the mitotic spindle in dividing cells passing through the M phase of mitosis, elimination of immature tumor blood vessels in rodent cancer models, and increased maturation of antigen presenting dendritic cells. The finding of increased maturation of dendritic cells provides strong justification for ongoing and reportedly planned clinical trials examining the ability of plinabulin to increase tumor antigen presentation, and in this way to boost the immune mediated killing of cancer cells when combined with immune checkpoint blockers (e.g. anti-PD1 and anti-CTLA4), with or without chemotherapy. The concordant increase in survival with reduction in a serious side effect of chemotherapy (i.e. neutropenia) when given in combination with plinabulin, is a rare achievement in cancer drug development; the mechanism underlying this combined benefit with plinabulin therapy is undergoing active scientific investigation.

Completed Clinical TrialsResults have been disclosed for the following clinical trials in which plinabulin was administered to human subjects:NCT00322608: Phase 1 trial testing Plinabulin monotherapy in advanced solid tumor malignancies or lymphoma, with safety evaluation as the primary objective.NCT00630110: Phase 1/2 trial testing Docetaxel versus Docetaxel+Plinabulin in advanced NSCLC, with demonstration of an overall survival benefit as the primary objective.

Ongoing Clinical TrialsThe following plinabulin clinical trials on https://clinicaltrials.gov/ are indicated to be ongoing: NCT02504489 (Dublin-3; Study 103): Phase 3 trial testing Docetaxel versus Docetaxel+Plinabulin in advanced NSCLC patients with measurable disease, utilizing demonstration of an overall survival benefit with plinabulin as the primary objective. NCT03102606 (Protective-1, Study 105): Phase 2/3 trial testing Docetaxel+Plinabulin versus Docetaxel+Pegfilgrastim in advanced NSCLC, with demonstration of a reduced duration of severe chemotherapy induced neutropenia (DSN) with plinabulin as the primary objective. NCT03294577 (Study 106): Phase 2/3 trial testing TAC+Plinabulin versus TAC+Pegfilgrastim in Her-2 negative breast cancer, with demonstration of a reduced duration of severe chemotherapy induced neutropenia (DSN) with plinabulin as the primary objective. NCT02812667: Phase 1 trial testing Nivolumab (Opdivo; anti-PD1) +Plinabulin in recurrent metastatic NSCLC, with safety evaluation as the primary objective. NCT02846792: Phase 1/2 trial testing Nivolumab (Opdivo; anti-PD1) +Plinabulin in recurrent or metastatic NSCLC, with the evaluation of safety and overall survival as the primary objectives.

Jamestonra34 (talk) 02:52, 4 July 2018 (UTC)

Plinabulin (chemical structure BPI-2358, formerly NPI-2358) is …

As I misunderstand it, a name like NPI-2358 is a provisional designation for Nereus Pharma's 2358th investigational drug candidate, saying nothing about its chemistry. —Tamfang (talk) 15:37, 18 September 2019 (UTC)

• What I think should be changed:

Current: "Plinabulin...is a small molecule under development by BeyondSpring Pharmaceuticals, and is in a world-wide Phase 3 clinical trial for non-small cell lung cancer."Request: "Plinabulin...is a small molecule under development by BeyondSpring Pharmaceuticals, having recently concluded a world-wide Phase 3 clinical trial for non-small cell lung cancer."

• Why it should be changed:

Plinabulin's Phase 3 clinical trial for non-small cell lung cancer has concluded, as seen in Reference 1.I request the body be updated to reflect this.

• References supporting the possible change (format using the "cite" button):

^[1]This is the same as the existing reference [1]. Please note the current link in Reference 1 is actually broken due to the inclusion of an extra period.

• What I think should be changed:

Nothing in the body, but citations for Reference 6 should be updated. I request changing the citation from the poster to these three papers.

• Why it should be changed:

Reference 6 cites a poster delivered at a conference, but there is no way to actually check this citation.Instead, the information of the poster is taken from three paper publications which are publicly available.

• References supporting the possible change (format using the "cite" button):

^[2]

^[3]

^[4]Wanchun28 (talk) 17:12, 15 May 2024 (UTC)