Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies

NCT04902040 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2020-0296NCI-2021-03489
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Clinical Stage IV Merkel Cell Carcinoma 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 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 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; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; 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; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• 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.

  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]).

  From the baseline tumor assessment through the last on-study tumor assessment for each participant, assessed up to 3 years

Study Arms (2)

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.

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.

Biological: Atezolizumab; Drug: Avelumab; Biological: Durvalumab; Biological: Nivolumab; Biological: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Arm A (radiation therapy, plinabulin, immunotherapy); Arm B (radiation therapy, immunotherapy)

Avelumab DRUG

Given IV

Also known as: Bavencio, MSB-0010718C, MSB0010718C

Arm A (radiation therapy, plinabulin, immunotherapy); Arm B (radiation therapy, immunotherapy)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Arm A (radiation therapy, plinabulin, immunotherapy); Arm B (radiation therapy, immunotherapy)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm A (radiation therapy, plinabulin, immunotherapy); Arm B (radiation therapy, immunotherapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm A (radiation therapy, plinabulin, immunotherapy); Arm B (radiation therapy, immunotherapy)

Plinabulin DRUG

Given IV

Also known as: NPI-2358

Arm A (radiation therapy, plinabulin, immunotherapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm A (radiation therapy, plinabulin, immunotherapy); Arm B (radiation therapy, immunotherapy)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Lung Neoplasms; Carcinoma, Renal Cell

Interventions

atezolizumab; avelumab; durvalumab; Immunoglobulin G; Disulfides; Nivolumab; pembrolizumab; NPI 2358; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Kidney Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Siqing Fu, MD,PHD
• Organization: The University of Texas MD Anderson Cancer Center

siqingfu@mdanderson.org

(713) 792-4318

Study Officials

• Siqing Fu, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 26, 2021
• Study Start: April 14, 2021
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2025
• Last Updated: April 30, 2026
• Results First Posted: March 18, 2026

Record last verified: 2026-04

Locations

US (1)