Docetaxel Plus Plinabulin vs Docetaxel Plus Placebo in Advanced/Metastatic Non-Squamous NSCLC After PD-1/PD-L1 Therapy and Platinum Chemotherapy (DUBLIN-4)

NCT07361484 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: BPI 2358 112
• Study Type: interventional
• Target: 442
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating docetaxel plus plinabulin versus docetaxel plus placebo in participants with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without EGFR, ALK, ROS1, or RET alterations who have experienced disease progression after prior anti-PD-1/PD-L1 immunotherapy and platinum-based chemotherapy. Approximately 442 participants will be randomized 1:1 to receive docetaxel (75 mg/m² IV on Day 1 of each 21-day cycle) in combination with plinabulin (30 mg/m² IV on Days 1 and 8) or matching placebo. Treatment will continue until disease progression, unacceptable toxicity, death, withdrawal of consent, or sponsor/investigator decision. Tumor assessments will be performed regularly per RECIST v1.1, and participants will be followed for survival after treatment discontinuation. The primary objective is to compare overall survival between treatment arms; secondary objectives include evaluation of progression-free survival, objective response rate, duration of response, disease control, incidence of Grade 4 neutropenia, quality of life, and safety/tolerability.

Conditions

Non-squamous Non-Small Cell Lung Cance; Non-Small Cell Lung Cancer

Keywords

Advanced NSCLC; Metastatic NSCLC; Non-squamous NSCLC; EGFR wild type; ALK wild type; ROS1 wild type; RET wild type; Docetaxel; Plinabulin; BPI-2358; DUBLIN-4

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS is defined as the time from randomization to death from any cause

  Approximately 2 years after study initiation.

Secondary Outcomes (10)

• Progression-Free Survival (PFS)

  Approximately 2 years after study initiation.

• Objective Response Rate (ORR)

  Approximately 2 years after study initiation.

• Incidence of Grade 4 Neutropenia (Cycle 1 Day 8 ANC)

  At Day 8 of Cycle 1 (approximately 1 week after the first dose; each treatment cycle is 21 days).

• Overall Survival (OS) Rate at Month 24

  24 months after randomization.

• Overall Survival (OS) Rate at Month 36

  36 months after randomization.

Other Outcomes (1)

• Metastasis-Free Survival (MFS)

  Approximately 2 years after study initiation.

Study Arms (2)

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.

Drug: Plinabulin; Drug: Docetaxel

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.

Drug: Docetaxel; Drug: Placebo (matching plinabulin placebo)

Interventions

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 + Plinabulin

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.

Docetaxel + Placebo; Docetaxel + Plinabulin

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.

Docetaxel + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females 18 years of age or older at the time of signing the ICF
• Willing and able to sign an ICF;
• 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 surgical treatment and have locally advanced (stage IIIb) or metastatic (stage IV) diseases, or have recurrent and progressive disease after local treatment (if there are multiple tumor components, classify the main cell type):
• Developed disease progression after treatment with PD-1/L1 inhibitors and platinum-based chemotherapy in advanced non-squamous NSCLC with EGFR, ALK, ROS and RET wild type
• Treatment progression with anti-PD-1/L1 inhibitors and platinum-based chemotherapy administered either concurrently or sequentially as part of the same first-line treatment plan, or as two separate prior lines of systemic therapy, (does not count preoperative and adjuvant therapy) is defined to meet all of the following criteria:
• Demonstrated disease progression after anti-PD-1/L1 and platinum-based chemotherapy concurrently or sequentially as defined by RECIST v1.1
• Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression. The disease progression to the first administration of the IMP should not exceed 60 days
• Achieved PFS of anti- PD-1/L1 treatment for at least 3 months
• ECOG performance status of 0 to 1
• All AEs from any previous systemic therapy, surgery or radiotherapy must have been resolved to CTCAE v5.0 Grade ≤1 or baseline
• Adequate organ function, within 7 days prior to administration of the IMP by the local laboratory:
• Hemoglobin ≥9 g/dL independent of transfusions or growth factor support
• ANC ≥1.5×109/L independent of growth factor support
• Platelet count ≥100×109/L independent of blood transfusion
• Serum total bilirubin ≤ the ULN, unless the participant has a diagnosis of Gilbert's disease in which case serum total bilirubin ≤3.0×ULN

You may not qualify if:

• Receipt of more than two prior lines of systemic anticancer therapy for locally advanced or metastatic non-small cell lung cancer. Neoadjuvant and adjuvant systemic therapies are not counted as prior lines of therapy
• Any of the following cardiac criteria experienced currently or within the last 6 months:
• Congestive heart failure (New York Heart Association ≥Class 2)
• Any clinically significant abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting ECGs, eg, complete left bundle branch block or third-degree heart block
• Acute coronary syndrome
• Clinically significant uncontrolled cardiac arrhythmia
• Any of the following cardiac criteria experienced currently:
• Mean QTC interval corrected (Friderica) \>470 ms
• Left ventricular ejection fraction \<50% or the lower limit of normal (per institutional standard)
• Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension (\>160 mmHg systolic and 100 mmHg diastolic in spite of anti hypertension medication), uncontrolled diabetes mellitus, active bleeding diatheses, as determined by the investigator
• Participants who have received prior treatment with docetaxel
• Prior transient ischemic attack or cerebrovascular accident within the past year
• History of hemorrhagic diarrhea, inflammatory bowel disease or active uncontrolled peptic ulcer disease (concomitant therapy with ranitidine or its equivalent and/or omeprazole or its equivalent is acceptable). History of ileus or other significant gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility
• Active bacterial, viral, or fungal infection requiring systemic therapy
• A current or a known history of acquired immunodeficiency syndrome-defining illness, or HIV infection with a CD4+ T-cell count \<350 cells/µL and an HIV viral load more than 400 copies/µL

Sponsors & Collaborators

• BeyondSpring Pharmaceuticals Inc.: lead

Related Links

• BEYONDSPRING PHARMACEUTICALS, INC. WEBSITE

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

NPI 2358; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Helen Li, MD

CONTACT

646-305-6387; helenli@beyondspringpharma.com

Hao Zhang

CONTACT

(646) 305-6387; Hzhang@beyondspringpharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2026
• First Posted: January 23, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 23, 2026

Record last verified: 2026-01