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.
PRIMARY OBJECTIVES:
I. 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:
I. 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:
I. 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.
V. 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.
Condition | Advanced Bladder Carcinoma, Advanced Lung Non-Small Cell Carcinoma, Advanced Malignant Solid Neoplasm, Advanced Melanoma, Advanced Merkel Cell Carcinoma, Advanced Renal Cell Carcinoma, Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Clinical Stage IV Merkel Cell Carcinoma AJCC v8, Pathologic Stage III Cutaneous Melanoma AJCC v8, Pathologic Stage III Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIA Cutaneous Melanoma AJCC v8, Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIB Cutaneous Melanoma AJCC v8, Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIC Cutaneous Melanoma AJCC v8, Pathologic Stage IIID Cutaneous Melanoma AJCC v8, Pathologic Stage IV Cutaneous Melanoma AJCC v8, Pathologic Stage IV Merkel Cell Carcinoma AJCC v8, Stage III Bladder Cancer AJCC v8, Stage III Lung Cancer AJCC v8, Stage III Renal Cell Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Bladder Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Bladder Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8 |
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Treatment | radiation therapy, Pembrolizumab, Nivolumab, Avelumab, durvalumab, Atezolizumab, Plinabulin |
Clinical Study Identifier | NCT04902040 |
Sponsor | M.D. Anderson Cancer Center |
Last Modified on | 4 October 2022 |
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