Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as BPI-2358, NPI-2358
Plinabulin · 5 trials · 5 indications
OS is defined as the time from randomization to death from any cause
Duration of severe neutropenia (ANC \< 0.5 × 109/L)
Duration of Grade 4 neutropenia (ANC \< 0.5 × 109/L)
Establish MTD of plinabulin in combination with nivolumab and ipilimumab for patients with recurrent SCLC. MTD reflects the highest dose of plinabulin that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined in accordance to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease(PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Progression Free Survival (PFS) is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.
| Arm | Type | Description |
|---|---|---|
| Docetaxel + Plinabulin | EXPERIMENTAL | Participants will receive docetaxel IV infusion on Day 1 of each 21-day cycle plus plinabulin IV infusion on Days 1 and 8. Treatment continues until disease progression, unacceptable toxicity, death, withdrawal, or sponsor/investigator decision. |
| Docetaxel + Placebo | PLACEBO_COMPARATOR | Participants will receive docetaxel IV infusion on Day 1 of each 21-day cycle plus matching placebo IV infusion on Days 1 and 8. Treatment continues until disease progression, unacceptable toxicity, death, withdrawal, or sponsor/investigator decision. |
| Docetaxel (75 mg/m2) + pegfilgrastim (6 mg) + placebo matching plinabulin | ACTIVE_COMPARATOR | Arm 1 |
| Docetaxel (75 mg/m2) + plinabulin (40 mg) + placebo matching pegfilgrastim | EXPERIMENTAL | Arm 2 |
| TAC + Pegfilgrastim (6 mg) | ACTIVE_COMPARATOR | - |
| TAC + Plinabulin 10 mg/m^2 | EXPERIMENTAL | - |
| TAC + Plinabulin 20 mg/m^2 | EXPERIMENTAL | - |
| TAC + Plinabulin 30 mg/m^2 | EXPERIMENTAL | - |
| TAC + Pegfilgrastim (1.5 mg) + Plinabulin (20 mg/m^2) | EXPERIMENTAL | - |
| TAC + Pegfilgrastim (3 mg) + Plinabulin (20 mg/m^2) | EXPERIMENTAL | - |
| TAC + Pegfilgrastim (6 mg) + Plinabulin (20 mg/m^2) | EXPERIMENTAL | - |
| 20 mg/m^2 Plinabulin | EXPERIMENTAL | 75 mg/m\^2 Docetaxel + 20 mg/m\^2 Plinabulin |
| 10 mg/m^2 Plinabulin | EXPERIMENTAL | 75 mg/m\^2 Docetaxel + 10 mg/m\^2 Plinabulin |
| 5 mg/m^2 Plinabulin | EXPERIMENTAL | 75 mg/m\^2 Docetaxel + 5 mg/m\^2 Plinabulin |
| 6 mg Pegfilgrastim | ACTIVE_COMPARATOR | 75 mg/m\^2 Docetaxel + 6 mg Pegfilgrastim |
| Phase I (Dose Escalation): nivolumab, ipilimumab and plinabulin | EXPERIMENTAL | On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 |
| Phase II: nivolumab, ipilimumab, and plinabulin | EXPERIMENTAL | On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (MTD from Phase I). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur . |
| Name | Type | Description |
|---|---|---|
| Plinabulin | DRUG | Plinabulin will be administered by IV infusion at 30 mg/m² over approximately 1 hour on Days 1 and 8 of each 21-day treatment cycle. On Day 1, plinabulin will be administered approximately 1 hour after completion of the docetaxel infusion. |
| Docetaxel | DRUG | Docetaxel will be administered by intravenous (IV) infusion at 75 mg/m² over approximately 1 hour on Day 1 of each 21-day treatment cycle. |
| Placebo (matching plinabulin placebo) | DRUG | Matching placebo will be administered by IV infusion over approximately 1 hour on Days 1 and 8 of each 21-day treatment cycle. On Day 1, placebo will be administered approximately 1 hour after completion of the docetaxel infusion. |
| Pegfilgrastim | DRUG | PEGFILGRASTIM is a long-acting granulocyte colony-stimulating factor that stimulates the growth of neutrophils, to reduce the incidence of fever and infection in patients with certain types of cancer who are receiving chemotherapy that affects the bone marrow. |
| Saline Placebo | OTHER | Placebo Syringe 0.6 ml Saline to match the 0.6 ml pegfilgrastim administration |
| D5W Placebo | OTHER | Placebo 250 ml D5W to match the administration of plinabulin diluted in 250 ml D5W |
| Docetaxel, doxorubicin, and cyclophosphamide (TAC) | DRUG | Docetaxel is a type of chemotherapy medicine called an taxane. Doxorubicin is a type of chemotherapy medicine called an anthracycline. Cyclophosphamide is a type of chemotherapy medicine called an alkylating agent. |
| Nivolumab | DRUG | A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. |
| Ipilimumab | DRUG | Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. |
Inclusion Criteria: 1. Males and females 18 years of age or older at the time of signing the ICF 2. Willing and able to sign an ICF; 3. Non-squamous NSCLC with EGFR, ALK, ROS and RET wild type who have been diagnosed by histopathological and/or cytological examination as being ineligible for surgic...
Plinabulin is an investigational small molecule developed by BeyondSpring, Inc. (ticker BYSI). It is being studied in chemotherapy-induced neutropenia and in lung cancer, including non-small cell lung cancer. It has received Breakthrough Therapy designation from the FDA and remains in clinical development.
Plinabulin is being developed to prevent chemotherapy-induced neutropenia in patients receiving myelosuppressive chemotherapy. Phase 2 trials have studied it in patients with solid tumors receiving docetaxel and in patients receiving TAC chemotherapy. It is investigational and has not been approved for this use.
Plinabulin is an inhibitor that targets tubulin proteins, including TUBB4B, TUBB1, TUBA3C, TUBA4A, TUBB3 and TUBA1A. By binding these tubulin targets, it interferes with microtubule dynamics in cells. This target class places Plinabulin among tubulin-binding small molecule agents.
Plinabulin is being developed by BeyondSpring, Inc., which trades under the ticker BYSI. The company sponsors the clinical program, including the Phase 3 DUBLIN-4 trial in non-small cell lung cancer and earlier Phase 2 studies in chemotherapy-induced neutropenia.
Plinabulin is in Phase 3 development. The Phase 3 DUBLIN-4 trial is registered but not yet recruiting, while three earlier Phase 1 and Phase 2 trials have been completed. Plinabulin is investigational and has not been approved by the FDA.
Plinabulin has been studied in several registered trials. These include NCT07361484, the Phase 3 DUBLIN-4 trial in advanced non-squamous NSCLC, NCT04345900 and NCT04227990 in chemotherapy-induced neutropenia, and NCT03575793 in recurrent small cell lung cancer. Total enrollment across these trials is 442 patients.