NCT05018273已完成1 期
A Phase 1B, Open-Label, Dose-Escalation Study of the Safety of and Antigen-specific Immune Responses Elicited by VB10.NEO in Combination With Atezolizumab in Patients With Locally Advanced and Metastatic Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 12
- 主要终点
- Incidence and severity of adverse events (AEs)
研究概览
简要总结
A phase 1b, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, antigen-specific immune response and preliminary antitumor activity associated with VB10.NEO administered in combination with atezolizumab, and to identify a RP2D for VB10.NEO in combination with atezolizumab, in patients with locally advanced and metastatic tumors that have progressed after at least 1 available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable, or is considered inappropriate; or for whom a clinical trial of an investigational agent is a recognized standard of care (SOC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Tumor types: melanoma, NSCLC, RCC, UC, HNSCC, TNBC, gastric/GEJ cancer, cervical, anal, or MSI-high tumors. Additionally up to 15 subjects with other locally advanced or metastatic solid tumor types not listed above.
- •Signed Informed Consent Form
- •Age ≥18 years at time of signing the Informed Consent Form
- •Ability to comply with the trial protocol
- •ECOG Performance Status of ≤ 1: Note: If ECOG Performance Status at Screen 2B assessment was performed > 7 days prior to VB10.NEO start date, it needs to be re-assessed on C1D1 prior to administration of VB10.NEO and remain ≤ 1
- •GRIm score ≤ 1 at Screen 1, this only applies for subjects initially screened under protocol version 5
- •Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior to initiation of trial treatment:
- •ANC ≥1.5 × 109/L (1500/µL) Must be met without administration of growth factors within 2 weeks prior to treatment start date.
- •Lymphocyte count ≥0.5 × 109/L (500/µL)
- •Platelet count 100-450 × 109/L (100,000 - 450,000/µL) Must be met without administration of platelet transfusion within 2 weeks prior to treatment start date.
- •Hemoglobin ≥90 g/L (9 g/dL) Must be met without erythropoietin dependency and without red blood cell transfusion within 2 weeks prior to treatment start date.
- •AST and ALT ≤3 × ULN
- •Alkaline phosphatase (ALP) ≤2.5 × ULN, with the following exceptions:
- •Subjects with documented liver or bone metastases: ALP ≤5 × ULN
- •Total bilirubin ≤1.5 × ULN with the following exception:
- •Subjects with known Gilbert disease: total bilirubin ≤3 × ULN
- •Measured or calculated creatinine clearance ≥50 mL/min (according to the Cockcroft-Gault formula)
- •Albumin ≥25 g/L (2.5 g/dL)
- •For subjects not receiving therapeutic anticoagulation: International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN
- •For subjects receiving therapeutic anticoagulation: stable anticoagulant regimen
- •Female subjects of childbearing potential must have a negative serum pregnancy test result within 72 hours prior to initiation of trial treatment.
- •Female subjects of childbearing potential must agree to use a highly effective form of contraception during treatment and for at least 90 days after the final dose of VB10.NEO, and for 5 months after the final dose of atezolizumab, whichever occurs later. Highly effective forms of contraception include:
- •combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
- •progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
- •intrauterine device
- •intrauterine hormone-releasing system
- •bilateral tubal occlusion
- •vasectomized partner
- •sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the trial treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence [calendar, symptothermal, post-ovulation methods], withdrawal [coitus interruptus], spermicides only, and the lactational amenorrhea method are not acceptable methods of contraception).
- •For men with a female partner of childbearing potential or pregnant female partner: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom during the treatment period and for at least 28 days after the final dose of trial treatment to avoid exposing the embryo, and agreement to refrain from donating sperm.
排除标准
- •Pregnant or breastfeeding, or intending to become pregnant during the trial or within 90 days after the last dose of VB10.NEO or 5 months after the last dose of atezolizumab, whichever occurs later
- •Significant cardiovascular disease such as, but not limited to, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
- •QT interval corrected through use of Fridericia's formula (QTcF) >470ms demonstrated by at least 2 electrocardiograms (ECGs) >30 minutes apart
- •Clinically significant liver disease including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse
- •Positive hepatitis B surface antigen (HBsAg) test at screening
- •Subjects with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive IgG antibody to hepatitis B core antigen) are eligible.
- •Positive hepatitis C virus (HCV) antibody test at screening
- •Subjects positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
- •Positive human immunodeficiency virus (HIV)-1 test at screening
- •Active tuberculosis
- •Any other diseases, metabolic dysfunction, physical examination finding, and/or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or may render the subject at high risk from treatment complications
- •Known primary immunodeficiencies
- •Active, or history of, autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
- •Subjects with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the trial.
- •Subjects with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the trial.
- •Subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., subjects with psoriatic arthritis are excluded) are eligible for the trial provided all of the following conditions are met:
- •Rash must cover <10% of body surface area
- •Disease is well controlled at baseline and requires only low potency topical corticosteroids
- •No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
- •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
- •Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.
- •Known allergy or hypersensitivity to any component of the VB10.NEO formulation.
- •History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on imaging conducted for tumor assessment at screening
- •History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- •History of drug-induced pneumonitis that was asymptomatic (defined by radiographic findings only) and reversible (without any anti-inflammatory therapies) is permitted.
- •Severe infection within 28 days prior to Cycle 1, Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- •Subjects receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease [COPD] exacerbation) are eligible for the trial.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •Subjects with indwelling catheters (e.g., PleurX) are allowed.
- •Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12 mg/dL, or corrected calcium >ULN)
- •Major surgical procedure within 28 days prior to Cycle 1, Day 1, or anticipation of need for a major surgical procedure during the course of the trial
- •Prior allogeneic stem cell or solid organ transplantation
- •Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 28 days or 5 drug-elimination half-lives (whichever is longer) prior to Cycle 1, Day 1
- •Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone >7.5 mg/day, cyclophosphamide, azathioprine, methotrexate, thalidomide, and tumor necrosis factor-alpha [TNF-α] antagonists) within 2 weeks prior to Cycle 1, Day 1 with the following exceptions:
- •Subjects who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the trial after medical monitor confirmation has been obtained
- •Subjects who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for COPD or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the trial.
- •Treatment with investigational therapy within 28 days prior to Cycle 1, Day 1
- •Live, attenuated vaccines are prohibited within 28 days prior to Cycle 1, Day 1, during atezolizumab treatment, and for 5 months after the final dose of atezolizumab
- •Vaccination with an approved COVID-19 vaccine that does not contain live, attenuated virus is permitted
研究组 & 干预措施
VB10.NEO 3 mg in combination with Atezolizumab 1200 mg
Experimental
VB10.NEO 3 mg will be administered by IM injection for an induction course Q3W (4 doses) followed by maintenance doses Q6W (6 doses) and Q12W (5 doses).
Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of 21 day cycles.
干预措施: VB10.NEO (Biological)
VB10.NEO 6 mg in combination with Atezolizumab 1200 mg
Experimental
VB10.NEO 6 mg will be administered by IM injection for an induction course Q3W (4 doses) followed by maintenance doses Q6W (6 doses) and Q12W (5 doses).
Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of 21 day cycles.
干预措施: VB10.NEO (Biological)
VB10.NEO 9 mg in combination with Atezolizumab 1200 mg
Experimental
VB10.NEO 9 mg will be administered by IM injection for an induction course Q3W (4 doses) followed by maintenance doses Q6W (6 doses) and Q12W (5 doses).
Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of 21 day cycles.
干预措施: VB10.NEO (Biological)
结局指标
主要结局
Incidence and severity of adverse events (AEs)
时间窗: From baseline and up to 27 months
The number and percentage of participants that experience an adverse event (AE)
Changes from baseline in vital signs
时间窗: From baseline and up to 27 months
Changes for measurements done prior and after the first VB10.NEO injection of each cycle for the following vital signs: Systolic blood pressure (mmHg); diastolic blood pressure (mmHg); pulse rate (bpm); respiration rate (breaths/min); body temperature (°C)
Changes from baseline in clinical laboratory parameters
时间窗: From baseline and up to 27 months
Changes for clinical laboratory parameters analysed locally prior and after the first VB10.NEO injection of each cycle, including hematology, chemistry panel, coagulation, thyroid function testing, C-reactive protein, urinalysis and serology
次要结局
- Duration of response (DOR)(From baseline and up to 27 months)
- Progression free survival (PFS)(From baseline and up to 27 months)
- Overall survival (OS)(From baseline and up to 27 months)
- Assessment of the antigen-specific immune response elicited by VB10.NEO administered in combination with atezolizumab(From baseline and up to 25 months)
- Characterize the pharmacokinetic of atezolizumab when administered in combination with VB10.NEO.(From baseline and up to 25 months)
- Objective response rate (ORR)(From baseline and up to 27 months)
- Evaluate the immune response to atezolizumab when administered in combination with VB10.NEO(From baseline and up to 25 months)
研究者
研究点 (12)
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