Advanced Bladder CarcinomaPhase 1/2NCT04902040
Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies
A Phase 1/2 study testing Atezolizumab, Avelumab and Durvalumab in people with Advanced Bladder Carcinoma and Advanced Lung Non-Small Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase Ib/II trial studies the side effects and best dose of plinabulin in combination with radiation therapy and immunotherapy in patients with select cancers that have spread to other places in the body (advanced) after progression on PD-1 or PD-L1 targeted antibodies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Bladder Carcinoma, Advanced Lung Non-Small Cell Carcinoma, Advanced Malignant Solid Neoplasm
- What is being tested?
- Atezolizumab, Avelumab and Durvalumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Apr 2021to 27 Feb 2025
- Phase
- Phase 1/2
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 must have one of seven histologically or cytologically confirmed malignant neoplasms (non-small cell lung cancer, small cell lung cancer, renal cell cancer, bladder cancer, Merkle cell cancer, microsatellite instability high (MSI-H) cancer (any histology), and melanoma) progressed on previous anti-PD-1/PD-L1 mAb treatment +/- chemotherapy or anti-CTLA4 requiring further treatment
- At least one lesion is amenable to radiation
- At least one additional non-contiguous lesion that has not been irradiated amenable to radiographic evaluation
- Have measurable disease based on immune-related response criteria (immune-related Response Evaluation Criteria In Solid Tumors [RECIST])
- Tissue must be newly obtained as a core needle biopsy (not fine-needle aspiration [FNA]) of the lesion being evaluated
- Age >= 18 years
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Subjects must be recovered from any prior major surgery. The major surgery must be performed at least 4 weeks prior to consent date
- Platelets >= 100 x 10^9/L
- Transfusions and growth factors are allowed
- Hemoglobin >= 9 g/dL
- Transfusions and growth factors are allowed
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Transfusions and growth factors are allowed
- White blood cell (WBC) >= 3 x 10^9/L
- Transfusions and growth factors are allowed
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (=< 1.5 x ULN if alkaline phosphatase is > 2.5 x ULN) (In the expansion cohort, subjects with known liver involvement may have ALT =< 5 x ULN)
- Alkaline phosphatase < 4 x ULN
- Total bilirubin =< 1 x ULN (In the expansion cohort, subjects with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of =< 3 x ULN)
- Albumin >= 3 g/dL
- Renal function defined as a calculated or measured glomerular filtration rate (GFR) >= 30 mL/min and Cockcroft-Gault equation
- The patient has recovered to grade =< 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of =< grade 2 specified elsewhere in these inclusion criteria
- Subjects must give informed consent according to the rules and regulations of the individual participating sites
- Negative urine pregnancy test in women of child bearing potential within 7 days of first dose of treatment and subjects of child-bearing potential must agree to use effective contraception during and for 5 months following the last dose of atezolizumab or nivolumab, and for 4 months after the last dose of pembrolizumab, and for 3 months after last dose of durvalumab and avelumab, and for 3 months after your last dose of plinabulin. A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices
Who cannot join
- Evidence of complete or partial bowel obstruction
- Subjects with primary central nervous system (CNS) tumor or CNS tumor involvement. However, subjects with metastatic CNS tumors may participate in this study if the patient is:
- > 4 weeks from prior therapy completion
- Clinically stable with respect to the CNS tumor at the time of study entry
- Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement
- Not receiving anti-convulsive medications (that were started for brain metastases)
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- Need of total parenteral nutrition
- Allergic to any of anti-PD-1/PD-L1 monoclonal antibody (mAb) intended to receive
- Prior exposure to plinabulin
- Pregnancy or lactation
- Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) =< 3 weeks prior to study drug administration date
- Chemotherapy, or immunotherapy or any other systemic anticancer therapy =< 3 weeks prior to study drug administration date except anti-PD-1/PD-L1 mAb mono or combination therapy
- Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated)
- Major surgery within four weeks before consent date
- Unstable cardiovascular function or active cardiac disease:
- Symptomatic ischemia (chest pain of cardiac origin),or
- Uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded; 1st degree AV block or asymptomatic Left anterior fascicular block (LAFB)/ right bundle branch block (RBBB) will not be excluded),or
- Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or
- Myocardial infarction (MI) within 3 months of consent date
- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose. Active infection with concurrent treatment is acceptable only if the patient is clinically stable
- Subject is known to be positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C
- Significantly diseased (as determined by the PI or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea. Presence of ileus or other significant gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility
- Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date
- Concurrent therapy with approved or investigational anticancer therapeutics
- Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 5 months following the last dose of atezolizumab or nivolumab, for 4 months after the last dose of pembrolizumab, and for 3 months after last dose of durvalumab and avelumab, and for 3 months after your last dose of plinabulin. Women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Single-Center, Phase 1b/2 Study to Evaluate the Safety of Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Malignancies After Progression on PD-1 or PD-L1 Targeted Antibodies
This phase Ib/II trial studies the side effects and best dose of plinabulin in combination with radiation therapy and immunotherapy in patients with select cancers that have spread to other places in the body (advanced) after progression on PD-1 or PD-L1 targeted antibodies. Plinabulin blocks tumor growth by targeting both new and existing blood vessels going to the tumor as well as killing tumor cells. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving plinabulin in combination with radiation therapy and immunotherapy may work better in treating advanced cancers.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability of plinabulin when administered in combination with radiation/immunotherapy regimen in subjects with select advanced solid malignancies after progression on anti-PD-1/PD-L1 monoclonal antibody (mAb).
II. To assess the objective tumor response rate (complete response + partial response).
SECONDARY OBJECTIVES:
- To assess disease control rate (complete response, partial response + stable disease).
II. To determine progression-free survival (PFS). III. To assess overall survival.
EXPLORATORY OBJECTIVES:
- To analyze the gene mutation density within each sample. II. To assess T-cell receptor (TCR) sequencing in tumor tissue and peripheral blood, pre- and post- treatment.
III. To perform imaging mass flow cytometry (CyTOF) and/or single cell ribonucleic acid sequencing (RNAseq) analysis on tumor tissue: Immune phenotyping, including dendritic cell (DC), T cells, tumor-associated macrophage (TAM)s, pre and post treatment.
IV. To conduct phenotyping analysis of immune cells from peripheral blood using multicolor flow cytometry.
- To evaluate dendritic cell activation from whole blood upon the treatment. VI. To explore general predictive and response biomarker measurements from the collected biomarkers.
OUTLINE: This is a phase Ib, dose-escalation study of plinabulin followed by a phase II study. Patients are randomized to 1 of 2 arms.
ARM A: Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients receive plinabulin intravenously (IV) over 30-60 minutes on days 1 and 4 of cycle 1, days 1 and 4 of cycle 2 (if receiving radiation therapy in cycle 2), and day 1 and or 15 (any day receiving immunotherapy) of subsequent cycles. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 months.
- Conditions
- Advanced Bladder Carcinoma, Advanced Lung Non-Small Cell Carcinoma, Advanced Malignant Solid Neoplasm, Advanced Melanoma, Advanced Merkel Cell Carcinoma, Advanced Renal Cell Carcinoma
- Being tested
- Atezolizumab, Avelumab, Durvalumab, Nivolumab, Pembrolizumab
- Medical subject headings
- Urinary Bladder Neoplasms, Lung Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabBiological
Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A
Given IV
AvelumabDrug
Also called Bavencio, MSB-0010718C, MSB0010718C
Given IV
DurvalumabBiological
Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736
Given IV
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
PlinabulinDrug
Also called NPI-2358
Given IV
Radiation TherapyRadiation
Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated
Undergo radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Arm A (radiation therapy, plinabulin, immunotherapy) | Experimental | Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients receive plinabulin IV over 30-60 minutes on days 1 and 4 of cycle 1, days 1 and 4 of cycle 2 (if receiving radiation therapy in cycle 2), and day 1 and or 15 (any day receiving immunotherapy) of subsequent cycles. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Atezolizumab; Drug: Avelumab; Biological: Durvalumab; Biological: Nivolumab; Biological: Pembrolizumab; Drug: Plinabulin; Radiation: Radiation Therapy |
| Arm B (radiation therapy, immunotherapy) | Active comparator | Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Atezolizumab; Drug: Avelumab; Biological: Durvalumab; Biological: Nivolumab; Biological: Pembrolizumab; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Tumor Response Rate (ORR) (Complete Response + Partial Response).
The number of patients who received treatment and have a partial or complete response to the treatment through study completion.
Measured: From the baseline tumor assessment through the last on-study tumor assessment for each participant, assessed up to 3 years
Secondary outcomes (1)
To Assess Disease Control Rate (Complete Response [CR] + Partial Response [PR] + Stable Disease [SD]).
The number of patients who received treatment and have a partial or complete response, or stabe disease to the treatment assessed according to irRECIST criteria through study completion.
Measured: From the baseline tumor assessment through the last on-study tumor assessment for each participant, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2021
- Study start14 Apr 2021
- Primary completion27 Feb 2025
- Study completion27 Feb 2025
Why it stopped: PI requested.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Bladder CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Siqing Fu, MD, PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04902040
- Sponsor's protocol ID
- 2020-0296
- Other IDs
- NCI-2021-03489, 2020-0296
- Status last verified
- Apr 2026
- First submitted
- 5 May 2021
- Last updated
- 30 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Lin SH, Subbiah V, Neri S, Cohen EN, Li Z, Lu YJ, Son YL, Lyu Y, Braun C, Gao H, Jayachandran G, Sharma A, Ye R, Fang P, Li N, Karp D, Hong D, Rodon J, Yu H, Peng J, Lloyd GK, Tonra JR, Reuben JM, Huang L, Fu S. Plinabulin following radiation enhances dendritic cell maturation and checkpoint inhibitor retreatment of relapsed/refractory cancers. Med. 2025 Oct 10;6(10):100752. doi: 10.1016/j.medj.2025.100752. Epub 2025 Jun 27.
PubMed 40580957