plinabulin (BPI 2358)

P1/2, N=39, Completed, Salma Sabbour | Active, not recruiting --> Completed

P1/2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=12 --> 19

Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population.

Plinabulin in combination with nivolumab and ipilimumab was tolerable at the dose of 30 mg/m2. While the clinical responses in PD-1 resistant SCLC were limited, some patients had a long duration of response. The number of ≥grade 3 irAE with the combination were lower than expected.

P1, N=18, Active, not recruiting, Lyudmila Bazhenova, M.D. | Trial completion date: Dec 2022 --> Jun 2025

P1/2, N=39, Active, not recruiting, Salma Sabbour | Trial completion date: Jan 2024 --> Jul 2024

P1/2, N=12, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1b/2 --> P1/2

P1/2, N=39, Active, not recruiting, Salma Sabbour | Recruiting --> Active, not recruiting | Trial completion date: Sep 2023 --> Jan 2024

Introduction: High dose melphalan with autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma is effective for disease control, but has a period of obligate neutropenia. The addition of plinabulin to pegfilgrastim did not add major toxicities after AHCT. Patients had elevated WBC on Day +2, low rates of NENF, and potentially less need for transfusion support. Plinabulin PK, quality of life data, and PROs will be presented.

P2, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=17, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024

Compound 11c also significantly induced G2/M cell cycle arrest and apoptosis in dose dependent manner. These results suggest that compound 11c might be a potential candidate for cancer treatment as antimicrotubule agent.

Multiple emerging agents show promise in decreasing the burden of CIN. Use of these therapies will reduce access disparities and will improve outcomes for patients with cancer receiving cytotoxic chemotherapy. Many ongoing trials are underway to evaluate the roles of these agents for more widespread use.

P1/2, N=35, Recruiting, Salma Sabbour | Trial primary completion date: Mar 2023 --> Sep 2023

Bone marrow suppression remains a common serious risk of classical/non-classical cancer drugs. Under these conditions, the addition of Plin offers rapid protection of GMP lineage cells which can be captured by simple blood cell counts. Incorporation of blood-based biomarkers may help enrich NSCLC pts with better sensitivity to Plin/Doc combination than Doc alone.

P2, N=47, Recruiting, Peking Union Medical College Hospital | Not yet recruiting --> Recruiting | Initiation date: Nov 2022 --> Feb 2023

This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first-line PD-1/PD-L1 inhibitor either as monotherapy or in combination with chemotherapy.

P2, N=47, Not yet recruiting, Peking Union Medical College Hospital

P3, N=559, Completed, BeyondSpring Pharmaceuticals Inc. | Active, not recruiting --> Completed

He was started on a treatment regimen of pembrolizumab and plinabulin (a phase I microtubule inhibitor) with radiation to the liver 2 months ago...After an initial period of observation, the patient was started on oral budesonide 9 mg/d and ursodiol 1000 mg/d for empiric treatment of IMH without subsequent improvement in liver enzymes...At the end of treatment, transaminases reached >5 times ULN. No improvement was seen in liver enzymes after initiating empiric steroid therapy for suspected IMH.

In this pilot trial (NCT05130827, a single dose of 40mg of intravenous plinabulin was given on day of stem cell infusion (Day 0) in conjunction with pegfilgrastim on Day +1 after high dose melphalan and AHCT with the primary objective to reduce the period of absolute neutropenia in patients with MM. To date, plinabulin appears well tolerated, and patients have not had non-engraftment related neutropenic fevers. Enrollment is ongoing, and full trial results will be presented.

We previously reported an OS, Safety, and QTWiST benefit with Plin/Doc vs Doc alone (ESMO 2021) in EGFR wild type 2nd/3rd line NSCLC pts from DUBLIN-3. Here, we report statistically significant QoL benefits with Plin/Doc vs Doc alone, as assessed with EORTC QLQ C30 and LC13, which may be relevant to guide treatment decisions in this generally sick patient population.

The addition of Plin to Doc was superior to SoC Doc alone for efficacy and safety in the clinically relevant subgroup of non-squamous EGFR-wild type, 2nd/3rd line NSCLC pts.

P2, N=15, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting

P2, N=15, Not yet recruiting, Memorial Sloan Kettering Cancer Center

The addition of Plin to Doc resulted in superior overall survival, safety and QoL vs Doc alone, offering 2nd/3rd line NSCLC pts the prospect of living longer and well.

Importantly, plinabulin induced a functional M1-like polarization of tumor infiltrating macrophages in murine tumors as well as in tumor samples from ovarian cancer patients, by preferentially triggering M1 proliferation. Our study uncovers a novel immunomodulatory effect of plinabulin in directly triggering M1 polarization and proliferation as well as promoting TAM anti-tumoral effector functions.

P3, N=559, Active, not recruiting, BeyondSpring Pharmaceuticals Inc. | Recruiting --> Active, not recruiting | Trial completion date: Nov 2020 --> Dec 2021

Results support the clinical testing of plinabulin as a non-G-CSF-based treatment for CIN associated with chemotherapies of different mechanisms. Results also support HSPC as a focal point for future mechanism-of-action work aimed at understanding the ability of plinabulin to reduce this serious side effect of cytotoxic therapy in cancer patients.

Following an Interim Analysis, the trial will continue without modifications. Research Funding: BeyondSpring Pharmaceuticals Inc

P3, N=554, Recruiting, BeyondSpring Pharmaceuticals Inc. | Trial completion date: Mar 2020 --> Jun 2020 | Trial primary completion date: Feb 2020 --> May 2020

P3, N=554, Recruiting, BeyondSpring Pharmaceuticals Inc. | Trial completion date: Nov 2019 --> Mar 2020 | Trial primary completion date: Oct 2019 --> Feb 2020

The confirmatory phase 3 portion of study 106 will test addition of Plin to Peg6, which may offer superior protection against TAC CIN vs Peg alone without bone pain. The Plin/Peg combination is a novel CIN approach with the potential to optimize chemotherapy, by minimizing chemotherapy dose modifications due to CIN or bone pain.*p<0.05; **p<0.001; ***P<0.01 Peg+Plin vs Peg 6mg