Non-small Cell Lung Cancer MetastaticPhase 1NCT02812667
Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)
A Phase 1 study testing Nivolumab + Plinabulin in people with Non-small Cell Lung Cancer Metastatic, run by Lyudmila Bazhenova, M.D. at 1 site in United States.
Trial summary
The purpose of the study is to determine whether plinabulin (also known as BPI-2358) has an effect on cancer and body in combination with nivolumab, a standard treatment for metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Metastatic
- What is being tested?
- Nivolumab + Plinabulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Aug 2016to 24 Oct 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with histologically or cytologically-confirmed metastatic NSCLC whose disease progressed during/after treatment with at least one platinum-containing chemotherapy regimen.
- At least 1 prior systemic therapy for metastatic disease. Adjuvant chemotherapy or concurrent chemoradiation for early stage disease does not count as prior therapy unless patients progressed within 6 months of completion of chemotherapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
- Life expectancy ≥ 12 weeks
- Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST).
- Adequate hematopoietic, electrolyte, hepatic, and renal laboratory findings.
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- Prior chemotherapy must have been completed at least 4 weeks or at least 5 half-lives (whichever is longer) before study drug administration, and all adverse events have either returned to baseline or stabilized
- Prior treated brain metastases are allowed. However, prior treated brain metastases must be without MRI evidence of progression for at least 4 weeks and off systemic steroids for at least 2 weeks before study drug administration
- Prior definitive radiation therapy must have been completed at least 4 weeks before study drug administration. Prior palliative radiotherapy should be completed at least 2 weeks before study drug administration. Whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and focal radiation to the sites of pain or bronchial obstruction will be considered palliative. No radiopharmaceuticals (strontium, samarium) within 8 weeks before study drug administration
- Prior major surgery must be completed at least 4 weeks before study drug administration. Prior minor surgery must be completed at least 1 week before study drug administration and subjects should be recovered. Percutaneous biopsies should be completed at least 10 days prior to study drug administration;
- A negative serum pregnancy test at screening for women of childbearing potential.
Who cannot join
- History of grade 3 or above hypersensitivity reactions to other monoclonal antibodies
- Subjects with a history of a cardiovascular illness.
- Uncontrolled hypertension, SBP> 160 or DBP>100
- Symptomatic or untreated brain metastases
- Presence of leptomeningeal disease
- Pulmonary conditions, which in the PI's opinion would increase the risk of immunotherapy-related pulmonary toxicity.
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- Has active, non-infectious pneumonitis
- Presence of a second malignancy, excluding non-melanomatous skin cancer unless in remission for 3 years
- Subjects with any active, known, or suspected autoimmune disease.
- History of ileus or other significant gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility.
- Prior therapy with microtubule destabilizing agents for NSCLC (ie. Vinorelbine)
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-stimulation pathways);
- Known history of Human Immunodeficiency Virus;
- Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
- Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events
- Concurrent medical condition requiring the use of immunosuppressive medications, or systemic steroids.
- Use of other investigational drugs within 28 days or at least 5 half-lives before study drug administration
- Pregnant or nursing
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Moores Cancer Center
La Jolla, California, 92093
About this study
Official title: A Phase I Study of Nivolumab in Combination With Escalating Doses of Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)
The purpose of the study is to determine whether plinabulin (also known as BPI-2358) has an effect on cancer and body in combination with nivolumab, a standard treatment for metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy.
Plinabulin inhibits tumor growth by targeting both new and existing blood vessels going to the tumor as well as killing tumor cells. Plinabulin is an investigational drug, a drug that is not approved for use outside of research studies by regulatory agencies. Up to 38 patients will be enrolled.
Read the detailed description
Plinabulin is a microtubule destabilizing agent (MDA) that inhibits the polymerization of tubulin monomers with resultant vascular disrupting properties. Plinabulin inhibits tumor growth by targeting both angiogenesis and tumor vasculature as well as directly by inducing apoptosis via the Ras-JNK pathway. It also may activate anti-tumor immunity via inducing maturation of dendritic cells (DC) and triggering release of pro-inflammatory cytokines. Plinabulin could therefore have a synergic anti-tumor effect when combined with immune-checkpoint inhibitors. This hypothesis has been confirmed in a murine model bearing subcutaneous MC38 colon cancers using other MDAs, including ansamitocin P3, which induces DC maturation similar to that of plinabulin. Plinabulin has been tested in a randomized phase 2 trial in combination of docetaxel and showed similar response rate to that of docetaxel alone, but with a significantly longer duration of response.
Nivolumab is an inhibitor of the programmed cell death receptor-1 checkpoint pathway (PD-1) that has superior activity in NSCLC, regardless of tumor histology, comparing to standard of care. In this study, we plan to combine nivolumab with escalating doses of plinabulin to determine the maximum tolerated dose (MTD) and /or recommended Phase 2 dose (RP2D) of the combination. An expansion cohort will be enrolled at RP2D to further assess toxicities and to evaluate preliminary anti-tumor activity.
This is a single-center, phase 1 dose finding trial of plinabulin, combining with FDA approved dose of nivolumab, using a 3+3 design in patients with metastatic NSCLC who progressed after chemotherapy, including a platinum-containing regimen. Patients will receive plinabulin at escalating doses in combination with nivolumab. Doses of plinabulin and nivolumab will be administered as intravenous infusions in 4-week cycles. Patients will receive both medications on Days 1 and 15 and additional dose of plinabulin on Day 8. Plinabulin will be administered 60 minutes after the completion of nivolumab.
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Being tested
- Nivolumab + Plinabulin
- Keywords
- Metastatic, NSCLC, nivolumab, plinabulin, BPI-2358, opdivo, Non-Small Cell Lung Cancer, cancer
- Medical subject headings
- Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab + PlinabulinDrug
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab + Plinabulin | Experimental | Nivolumab 240mg IV, day 1 and 15 until disease progression Plinabulin 3.5mg/m2, 20mg/m2, 30 mg/m2 or 40mg/m2 IV, day 1,8 and 15 until disease progression Receives: Drug: Nivolumab + Plinabulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
Measured: 2 years
Frequency and severity of treatment-related adverse events as assessed by CTCAE v4.
Measured: 2 years
Secondary outcomes (4)
Objective response rate (ORR)
Measured: 2 years
Disease control rate (DCR)
Measured: 2 years
Progression free survival (PFS)
Measured: 2 years
Overall survival (OS)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2016 (estimated)
- Study start29 Aug 2016
- Primary completion24 Nov 2024
- Study completion24 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lyudmila Bazhenova, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- BeyondSpring Pharmaceuticals Inc.
- Responsible party
- Sponsor-investigator, Lyudmila Bazhenova, M.D., University of California, San Diego
- Investigators
- Lyudmilla Bazhenova, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02812667
- Sponsor's protocol ID
- 160186
- Status last verified
- Nov 2025
- First submitted
- 22 Jun 2016
- Last updated
- 12 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Nivolumab in Combination With Escalating Doses of Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT02812667
- Acronym / sponsor ID
- 160186
- Conditions
- Non-small Cell Lung Cancer Metastatic
- Keywords
- Metastatic, NSCLC, nivolumab, plinabulin, BPI-2358, opdivo, Non-Small Cell Lung Cancer, cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Lyudmila Bazhenova, M.D.University, hospital or other
- Collaborators
- BeyondSpring Pharmaceuticals Inc.
- Study start
- 29 Aug 2016 (actual)
- Primary completion
- 24 Nov 2024 (actual)
- Study completion
- 24 Oct 2025 (actual)
- First posted
- 24 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to determine whether plinabulin (also known as BPI-2358) has an effect on cancer and body in combination with nivolumab, a standard treatment for metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy.
Plinabulin inhibits tumor growth by targeting both new and existing blood vessels going to the tumor as well as killing tumor cells. Plinabulin is an investigational drug, a drug that is not approved for use outside of research studies by regulatory agencies. Up to 38 patients will be enrolled.
Detailed description
Plinabulin is a microtubule destabilizing agent (MDA) that inhibits the polymerization of tubulin monomers with resultant vascular disrupting properties. Plinabulin inhibits tumor growth by targeting both angiogenesis and tumor vasculature as well as directly by inducing apoptosis via the Ras-JNK pathway. It also may activate anti-tumor immunity via inducing maturation of dendritic cells (DC) and triggering release of pro-inflammatory cytokines. Plinabulin could therefore have a synergic anti-tumor effect when combined with immune-checkpoint inhibitors. This hypothesis has been confirmed in a murine model bearing subcutaneous MC38 colon cancers using other MDAs, including ansamitocin P3, which induces DC maturation similar to that of plinabulin. Plinabulin has been tested in a randomized phase 2 trial in combination of docetaxel and showed similar response rate to that of docetaxel alone, but with a significantly longer duration of response.
Nivolumab is an inhibitor of the programmed cell death receptor-1 checkpoint pathway (PD-1) that has superior activity in NSCLC, regardless of tumor histology, comparing to standard of care. In this study, we plan to combine nivolumab with escalating doses of plinabulin to determine the maximum tolerated dose (MTD) and /or recommended Phase 2 dose (RP2D) of the combination. An expansion cohort will be enrolled at RP2D to further assess toxicities and to evaluate preliminary anti-tumor activity.
This is a single-center, phase 1 dose finding trial of plinabulin, combining with FDA approved dose of nivolumab, using a 3+3 design in patients with metastatic NSCLC who progressed after chemotherapy, including a platinum-containing regimen. Patients will receive plinabulin at escalating doses in combination with nivolumab. Doses of plinabulin and nivolumab will be administered as intravenous infusions in 4-week cycles. Patients will receive both medications on Days 1 and 15 and additional dose of plinabulin on Day 8. Plinabulin will be administered 60 minutes after the completion of nivolumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab + Plinabulin | Experimental | Drug: Nivolumab + PlinabulinNivolumab 240mg IV, day 1 and 15 until disease progression Plinabulin 3.5mg/m2, 20mg/m2, 30 mg/m2 or 40mg/m2 IV, day 1,8 and 15 until disease progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects with histologically or cytologically-confirmed metastatic NSCLC whose disease progressed during/after treatment with at least one platinum-containing chemotherapy regimen.
- At least 1 prior systemic therapy for metastatic disease. Adjuvant chemotherapy or concurrent chemoradiation for early stage disease does not count as prior therapy unless patients progressed within 6 months of completion of chemotherapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
- Life expectancy ≥ 12 weeks
- Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST).
Key exclusion criteria (18 listed)
- History of grade 3 or above hypersensitivity reactions to other monoclonal antibodies
- Subjects with a history of a cardiovascular illness.
- Uncontrolled hypertension, SBP> 160 or DBP>100
- Symptomatic or untreated brain metastases
- Presence of leptomeningeal disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab + Plinabulin | Drug | Nivolumab + Plinabulin |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: 2 years
Frequency and severity of treatment-related adverse events as assessed by CTCAE v4.
Time frame: 2 years
4 secondary outcomes
Objective response rate (ORR)
Time frame: 2 years
Disease control rate (DCR)
Time frame: 2 years
Progression free survival (PFS)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lyudmilla Bazhenova, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab + Plinabulin in people with Non-small Cell Lung Cancer Metastatic, run by Lyudmila Bazhenova, M.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2025.