PNV21-001: A Phase I Study of a Personalized Multi-Peptide Neo-Antigen Vaccine in Breast Cancer, PD1/PD-L1 Inhibitor-Refractory Melanoma, and Pretreated Non-Small Cell Lung Cancer
概览
- 阶段
- 1 期
- 干预措施
- Neoantigen Peptide Vaccine
- 疾病 / 适应症
- 未指定
- 发起方
- Fred Hutchinson Cancer Center
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
This phase I trial studies the safety of personalized neo-antigen peptide vaccine in treating patients with stage IIIC-IV melanoma, hormone receptor positive HER2 negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or does not respond to treatment (refractory) or stage III-IV non-small cell lung cancer. Personalized neo-antigen peptide vaccine is a product that combines multiple patient specific neo-antigens. Given personalized neo-antigen peptide vaccine together with Th1 polarizing adjuvant poly ICLC may induce a polyclonal, poly-epitope, cytolytic T cell immunity against the patient's tumor.
详细描述
OUTLINE: Patients receive poly ICLC intramuscularly (IM) once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab intravenously (IV) every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo tumor biopsy, blood sample collection, and computed tomography (CT) and/or positron emission tomography (PET) throughout the study. After completion of study treatment, patients are followed up at 24, 36, and 48 weeks. Patients who do not have disease progression and continue nivolumab monotherapy or off treatment will continue post-treatment follow up for an additional 12 months.
研究者
入排标准
入选标准
- •Female and/or male patients age \>= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- •Patients must have at least 1 lesion (or aggregate lesions) to obtain tumor tissue for resection of \>= 1 cm or \>= 4 core biopsies acceptable. Amenable to image (CT, ultrasound \[U/S\], or magnetic resonance imaging \[MRI\]) guided biopsy for tissue collection necessary for neoantigen identification. Either primary or metastatic sites are options for tissue collection
- •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm, unless lymph node in which case short axis must be \>= 15 mm. Baseline imaging (for example diagnostic CT chest/abdomen/pelvis, PET CT scan and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) must be obtained within 45 days of prior to start of first planned vaccine dose infusion. MRI can be substituted for CT in patients unable to have CT contrast
- •Serum creatine \< 1.5 mg/dL or estimated glomerular filtration rate (eGFR) \> 60 mL/min
- •Total bilirubin (tBili) \< 1.5 x upper limit of normal (ULN) and an aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 2.5 x ULN and \< 5 x ULN for subjects with documented liver metastasis. Patients with suspected Gilbert syndrome may be included if tBili \> 3 but no other evidence of hepatic dysfunction
- •=\< grade 1 dyspnea and arterial oxygen saturation (SaO2) \>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, patients with forced expiratory volume in 1 second (FEVI) \>= 70% of predicted and carbon monoxide diffusing capability (DLCO) (corrected) of \>= 60% of predicted will be eligible
- •Patients with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids will be excluded
- •Patients 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \>= 50%. Cardiac evaluation for other patients is at the discretion of the treating physician
- •Subjects with a history of myocarditis or congestive heart failure (as defined by New York Heart Association functional classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry will be excluded
排除标准
- •Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 5 months after the last dose of investigational product
- •Any history of an immune-related grade 4 adverse event attributed to prior cancer immunotherapy CIT (other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase)
- •Any history of an immune-related grade 3 adverse event attributed to prior CIT that required permanent discontinuation of PD-1 inhibitor therapy
- •Immune-related adverse events related to prior CIT (other than endocrinopathy managed with replacement therapy or stable vitiligo) that have not resolved to baseline. Patients treated with corticosteroids for immune-related adverse events must demonstrate absence of related symptoms or signs for \>= 4 weeks following discontinuation of corticosteroids
- •Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated \> 4 weeks prior to enrollment. Patients should be recovered from the effects of radiation
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed
- •Patients with known symptomatic brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable for \>= 1 months (confirmed by magnetic resonance imaging \[MRI\])
- •Patients with rapidly progressing disease, symptomatic visceral disease, or patients who are expected to have rapidly progressive disease over the course of several months despite bridging therapy approved by the protocol
- •Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency \[SCID\]) or combined T- and B-cell immunodeficiencies (e.g., T- and B-negative SCID, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency)
- •Prior allogeneic bone marrow transplantation or prior solid organ transplantation
研究组 & 干预措施
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Neoantigen Peptide Vaccine
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Nivolumab
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Poly ICLC
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Echocardiography
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Multigated Acquisition Scan
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Biopsy
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Biospecimen Collection
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Computed Tomography
Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)
Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.
干预措施: Positron Emission Tomography
结局指标
主要结局
Incidence of adverse events
时间窗: 1 year post first vaccination
Will be assessed by Common Terminology Criteria for Adverse Events version 5.0.
次要结局
- Number of formulated and administered personalized neo-antigen vaccines(Week 48)
- Number of formulated personalized neo-antigen vaccines with at least five (5) vaccine peptides(Week 48)
- Number of formulated personalized neo-antigen vaccines in less than 16 weeks since screening visit biopsy(16 weeks)
- Evaluation of target lesion(At 1 year post first vaccination)
- Best overall response(1 year post first vaccination)
- Progression-free survival(1 year post first vaccination)