A Randomized Phase 2 Study Assessing the Efficacy and Safety of Olvimulogene Nanivacirepvec Followed by Platinum-doublet Chemotherapy + Physician's Choice of Immune Checkpoint Inhibitor Compared With Docetaxel in Patients With NSCL Cancer After First Progression While on Front-line Immune Checkpoint Inhibitor-based Maintenance
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 142
- 试验地点
- 30
- 主要终点
- Progression-free Survival per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Blinded Independent Central Review (BICR)
研究概览
简要总结
This Phase 2, open-label, randomized study in non-small-cell lung cancer (NSCLC) is designed to evaluate the efficacy and safety of an intravenously delivered oncolytic vaccinia virus, Olvi-Vec, followed by platinum-doublet chemotherapy + Physician's Choice of Immune Checkpoint Inhibitor (ICI) vs. docetaxel for patients with advanced or metastatic NSCLC who have shown first disease progression (i.e., progressive disease not yet confirmed by further scan after initial scan showing progression) while on front-line treatment or maintenance ICI therapy after front-line treatment with platinum-doublet chemotherapy + ICI as standard of care.
详细描述
Olvi-Vec (olvimulogene nanivacirepvec, aka GL-ONC1; laboratory name: GLV-1h68) is an oncolytic vaccinia virus-based immunotherapy that has been shown to have broad infectivity in a wide range of tumor types including non-small-cell lung cancer (NSCLC). In preclinical studies, Olvi-Vec was shown to infect and kill NSCLC cells and tumors in vitro and in vivo, respectively, and resolved and prevented formation of malignant effusion. This study is to test the hypothesis that the combination of Olvi-Vec followed by further platinum-based chemotherapy plus an ICI is particularly effective against established tumors by virus-mediated immune activation and re-sensitization of tumor cells to chemotherapy. Participants will have advanced or metastatic NSCLC (Stage III or Stage IV) squamous or nonsquamous disease without known targetable alterations in Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) or Repressor of Silencing 1 (ROS1). Eligible patients will have first disease progression by radiological assessment (i) while on front-line platinum-doublet chemotherapy and ICI, or (ii) while receiving front-line maintenance ICI-based therapy after completion of front-line therapy, with at least 2 cycles and maximum of 6 cycles of platinum-doublet chemotherapy and ICI, regardless of Programmed death-ligand 1 (PD-L1) expression as the first treatment after being diagnosed. ICI includes anti-programmed death-1 (anti-PD-1) or anti-PD-L1 agents. Other classes of ICI [e.g., anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), etc.] are excluded. Patients will be stratified based on length of time on ICI-based therapy from start date of the first dose, if ICI during front-line therapy, until date of first progression by radiological assessment is either less than or equal to 4 months or greater than 4 months. Patients enrolled in one of the initial 3 cohorts will receive either 3 or 4 days of Olvi-Vec followed by platinum-doublet chemotherapy + Physician's Choice of ICI. The randomization part of the study will start afterwards with the Olvi-Vec dose and schedule selected from one of the 3 cohorts for the Experimental Arm. The Active Comparator Arm (ACA) treatment includes docetaxel. Participants treated in the ACA who subsequently have documented disease progression may cross-over for treatment as per the Experimental Arm following determination of eligibility.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Male or female 18 years or older.
- •ECOG (Eastern Cooperative Oncology Group) performance status of 0 or
- •Have histologically or cytologically confirmed advanced or metastatic NSCLC.
- •Histologically confirmed Stage III or IV squamous or nonsquamous [American Joint Committee on Cancer (AJCC) 8th edition].
- •Received at least 2 cycles and maximum of 6 cycles of front-line platinum-based chemotherapy with ICI-based therapy, regardless of PD-L1 expression.
- •Reached first disease progression by radiological assessment while receiving front-line or maintenance ICI.
- •At least one measurable target tumor lesion anywhere except the brain per RECIST 1.1 by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan.
- •Have adequate renal, hepatic, bone marrow function as well as adequate coagulation tests [International Normalized Ratio (INR)] and adequate immune function by lymphocyte count.
- •Women of child-bearing potential must have a negative serum pregnancy test prior to initiating study dosing.
- •Be willing and able to comply with scheduled visits, the treatment plan, imaging and laboratory tests.
排除标准
- •Active and untreated urinary tract infection, pneumonia, or other systemic infections.
- •Current symptomatic central nervous system (CNS) metastasis.
- •Any uncontrolled systemic disease, condition or comorbidity that, in the opinion of the Investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
- •Persistent toxicities [Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3] caused by previous anticancer therapy; alopecia and vitiligo are excluded toxicities.
- •Required the use of additional immunosuppression other than corticosteroids for the management of an adverse event or have experienced recurrence of an adverse event if re-challenged, or currently require maintenance doses of >10 mg prednisone or equivalent per day.
- •Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, tecovirimat, or other agents with known anti-vaccinia activities).
- •Underwent major surgery within 4 weeks, or have insufficient recovery from surgical-related trauma or wound healing, prior to the planned first dose of treatment in either Arm.
- •Have received prior virus-based gene therapy or therapy with cytolytic virus of any type.
- •Vaccination against smallpox or monkeypox within 1 year of study therapy.
- •Any non-oncology vaccine therapy used for prevention of infectious diseases, such as seasonal (influenza) vaccinations, corona virus disease (COVID) vaccination or other vaccines, within 2 weeks of the planned first dose of study drug.
- •Clinically significant skin disease as assessed by the Investigator (e.g., severe eczema, psoriasis, or any unresolved skin injury or ulcer).
- •Known hypersensitivity to carboplatin, cisplatin, paclitaxel or nab-paclitaxel, docetaxel, or any of the constituents of Olvi-Vec (i.e., gentamicin).
- •Had severe hypersensitivity (CTCAE Grade ≥ 3) to ICI and/or any of its excipients previously.
- •Dementia or altered mental status that would prohibit informed consent, and/or psychiatric illness/social situations that might interfere or limit compliance with study requirements.
研究组 & 干预措施
Experimental Arm
Olvi-Vec will be administered at the dose and schedule selected from the single-arm run-in Olvi-Vec dose escalation cohorts followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.
干预措施: Olvimulogene nanivacirepvec (Biological)
Active Comparator Arm
Docetaxel starts in Week 0 and continues until disease progression is assessed by the BICR.
干预措施: Docetaxel (Drug)
Single-arm run-in Olvi-Vec dose escalation Cohorts
Cohort 1: Olvi-Vec administered over 3 consecutive days at 0.5,0.5,0.5 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.
Cohort 2: Olvi-Vec administered over 3 consecutive days at 1,1,1 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.
Cohort 3: Olvi-Vec administered over 4 consecutive days at 1,2,3 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.
干预措施: Olvimulogene nanivacirepvec (Biological)
Active Comparator Arm Cross-over
Patients randomized into the Active Comparator can cross-over to receive the same treatment as given in the Experimental Arm following determination of (1) disease progression by BICR after receiving docetaxel treatment and (2) confirming eligibility.
干预措施: Olvimulogene nanivacirepvec (Biological)
Active Comparator Arm Cross-over
Patients randomized into the Active Comparator can cross-over to receive the same treatment as given in the Experimental Arm following determination of (1) disease progression by BICR after receiving docetaxel treatment and (2) confirming eligibility.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Progression-free Survival per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Blinded Independent Central Review (BICR)
时间窗: From date of randomization up to 12 months.
To assess progression-free survival from time of randomization until first documented disease progression based on radiological assessment or death from any cause.
次要结局
- Six-month Progression-free Survival Rate(From date of randomization up to 6 months.)
- Incidence of Treatment-emergent Adverse Events(Assessed up to 36 months.)
- Disease Control Rate (DCR)(From date of randomization up to 12 months.)
- Median Overall Survival(From date of randomization up to 36 months.)
- Objective Response Rate (ORR) by RECIST 1.1(From date of randomization up to 12 months.)
- Duration of Response by RECIST 1.1(From date of randomization up to 12 months.)