CTRI/2024/10/075387尚未招募3 期
A Phase III, Two-Arm, Parallel, Randomized, Multi-Center, Open-Label, Global Study to Determine the Efficacy of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer (mNSCLC) (eVOLVE-Lung02)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 900
- 试验地点
- 10
- 主要终点
- Dual Primary
研究概览
简要总结
This is a Phase III, randomized, multicenter study of volrustomig plus chemotherapy versus active comparator pembrolizumab plus chemotherapy as a 1L treatment for participants with mNSCLC and PD-L1 expression on less than 50 percentage of tumor cells (PD-L1 TC< 50 percentage). This study will be conducted in approximately 230 sites across 30 countries. Participants must have tumors that lack EGFR mutations and ALK and ROS1 rearrangements; in addition, tumors must not have any documented actionable genomic alterations identified by local standard practice for which there are locally approved 1L targeted therapies. During the 28-day screening period, mandatory tumor samples will be collected for prospective assessment of PD-L1 as measured using the VENTANA PD-L1 (SP263) Assay via a central reference laboratory. Only participants in the PD-L1 TC< 50 percentage population will be eligible to continue in the study. Following screening, eligible participants will be randomized 1:1 to either volrustomig plus chemotherapy or pembrolizumab plus chemotherapy; randomization will be stratified by histology, PD-L1 status, smoking history, and region of enrollment. At least 600 of the 900 randomized participants must be PD-L1 TC< 1 percentage; the remainder will be PD-L1 TC 1 percentage to 49 percentage. After the last dose of study intervention, all participants will undergo an end-of-treatment visit (within 21 [+ 7 days] of discontinuation) and will be followed up for safety assessments 90 days (± 7 days) after their last dose of study intervention (ie, the safety follow-up visit). In addition, all participants will be followed up for survival status after discontinuation of study intervention every 56 days (8 weeks) ± 14 days up to 3 years and then every 84 days (12 weeks) ± 14 days thereafter from the date of discontinuation until death, withdrawal of consent, or the end of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion Criteria Participant must be 18 years at the time of screening.
- •All races, genders, and ethnic groups are eligible for this study.
- •Stage IV NSCLC not amenable to curative surgery or radiation.
- •Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements.
- •Absence of documented tumor genomic alteration results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted first-line therapies.
- •Provision of tumor sample during screening to assess the PD L1 status, confirmed by a central reference laboratory using the VENTANA PD-L1 (SP263) Assay.
- •All participants must be able to undergo a fresh tumor biopsy during screening or to provide an available tumor sample taken 3 months prior to screening for analysis.
- •Tumor PD L1 TC expression 50 percentage as determined using the VENTANA PD-L1 (SP263) Assay by a central reference laboratory.
- •PD-L1 status must be known prior to randomization.
- •Participants with PD-L1 TC 50 percentage or indeterminate/unevaluable result are not eligible for the study.
- •At least one measurable lesion not previously irradiated, that can be accurately assessed at baseline ECOG performance status 0 or 1 Life expectancy 12 weeks.
- •Adequate organ and bone marrow function Body weight 35 kg at screening and randomization.
- •Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Capable of giving signed informed consent.
- •Provision of signed and dated written Optional Genetic Research Information informed consent.
排除标准
- •Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1 Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant. Rare subtypes (eg, NUT carcinoma, thoracic SMARCA4-deficient undifferentiated tumor, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma) are excluded. 2 Spinal cord compression. 3 Brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment. 4 History of another primary malignancy except for: (a) Malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. (b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. (c) Adequately treated carcinoma in situ without evidence of disease. 5 As judged by the investigator, any condition that would interfere with evaluation of the study intervention or interpretation of participant safety or study results. 6 Evidence of the following infections: (a) Active infection including tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination, and radiographic findings and TB testing in line with local practice), (b) Known human immunodeficiency virus (HIV) infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load for 6 months, CD4 Plus count of 500 cells/μL, stable for at least 6 months on the same anti-HIV medications, and no history of AIDS (either CD4 Plus T cell count 200 cells/μL and/or AIDS-defining opportunistic infection), (c) or active or uncontrolled hepatitis B (HBV) or hepatitis C (HCV); Participants are eligible if they: Have controlled hepatitis C viral load defined as undetectable hepatitis C RNA by PCR either spontaneously or in response to a successful prior course of anti-hepatitis C therapy.
- •Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis.
- •Are HBsAg- and anti-HBc Plus (ie, those who have cleared HBV after infection) and meet conditions i-iii below: Are HBsAg with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below: (i) HBV DNA viral load 100 IU/mL (ii) Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of AST/ALT 3 ULN, which are not attributable to HBV infection (iii) Start or maintain antiviral treatment if clinically indicated as per the investigator (d) or active hepatitis A 7 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including, but not limited to, ongoing or active infection, cardiomyopathy of any etiology, symptomatic congestive heart failure [as defined by New York Heart Association class 2], uncontrolled hypertension, unstable angina pectoris, history of myocardial infarction within the past 12 months, ILD, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations, and active bleeding diseases) and/or history of organ transplant or allogenic stem cell transplant, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol. 8 History of primary active immunodeficiency. 9 Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease eg colitis or Crohns disease diverticulitis with the exception of diverticulosis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves disease, rheumatoid arthritis, hypophysitis, uveitis, pneumonitis past medical history of ILD, drug-induced ILD, or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD, etc. The following are exceptions to this criterion: (a) Participants with vitiligo or alopecia. (b) Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. (c) Any chronic skin condition that does not require systemic therapy. (d) Participants without active disease in the last 5 years prior to enrolment may be included. (e) Participants with celiac disease controlled by diet alone. 10 Participant meets one or more of the following: (a) History of QT prolongation associated with other medications that required discontinuation of that medication. (b) Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives. (c) History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on the investigator judgement with cardiologist consultation recommended. 11 Medical contraindication to platinum-based doublet chemotherapy. Prior/Concomitant Therapy 12 Prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines. 13 Prior chemotherapy or any other systemic therapy for Stage IV NSCLC. Participants who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred 12 months from end of last therapy. 14 Persistent toxicities (CTCAE Grade 2) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included (eg, hearing loss). 15 Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, insulin for diabetes, HRT, gonadotropin-releasing hormone analogs, and bisphosphonates) is acceptable. 16 Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30 of the bone marrow within 4 weeks, prior to the first dose of study intervention. Note: Local treatment of isolated lesions for palliative intent is acceptable. 17 Any concomitant medication known to be associated with Torsades de pointes. 18 Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention is excluded. The following are exceptions to this criterion : (a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection). (b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication), as premedication for chemotherapy, or a single dose for palliative purpose (eg, pain control). 19 Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention are excluded 20 Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks prior to the first dose of study intervention or still recovering from prior surgery. Note: Local surgery of isolated lesions for palliative intent is acceptable. 21 Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.
结局指标
主要结局
Dual Primary
时间窗: PFS Measured by HR | Time Frame: upto approx. 57 months | OS Measured by HR | Time Frame: upto approx. 57 months
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS in participants where PD-L1 TC 1%.
时间窗: PFS Measured by HR | Time Frame: upto approx. 57 months | OS Measured by HR | Time Frame: upto approx. 57 months
To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS in participants where PD-L1 TC 1%.
时间窗: PFS Measured by HR | Time Frame: upto approx. 57 months | OS Measured by HR | Time Frame: upto approx. 57 months
次要结局
- To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS in all randomized participants.(The measure of interest is the HR of PFS.)
- To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS in all randomized participants.(The measure of interest is the HR of OS.)
- To demonstrate and characterize the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS landmarks.(The measures of interest are the landmarks of PFS6, PFS12, PFS18, and PFS24.)
- To demonstrate and characterize the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS landmarks.(The measures of interest are the landmarks of OS12, OS18, OS24, and OS36.)
- To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by investigator assessment of PFS.(PFS by investigator assessment, in participants with PD-L1 TC 1 percentage and in all randomized participants.)
- To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of ORR in participants(ORR in participants with PD-L1 TC 1 and in all randomized participants.)
- To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of DoR in participants.(DoR in participants with PD-L1 TC 1 percentage and in all randomized participants.)
- To demonstrate the efficacy of volrustomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS2 in participants.(PFS2 in participants with PD-L1 TC 1 percentage and in all randomized participants.)
- To assess the PK of volrustomig.(Concentration of volrustomig in serum and PK parameters (such as peak concentration and trough, as data allow; sparse sampling).)
- To investigate the immunogenicity of volrustomig(Presence of ADAs against volrustomig in serum (confirmatory results: positive or negative, titers).)
- To assess participant-reported functioning and HRQoL in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy(Change from baseline and TTD of functioning and overall global health status/QoL scores)
- To assess participant-reported physical functioning in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy.(To assess participant-reported physical functioning in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy.)
- To assess participant-reported pulmonary symptoms of mNSCLC in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy.(TTD in pulmonary symptoms as measured by the NSCLC SAQ.)
- To assess the safety and tolerability of volrustomig plus chemotherapy compared with pembrolizumab plus chemotherapy in participants with mNSCLC.(Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE version 5.0), vital signs, clinical laboratory assessments, physical examinations, and electrocardiograms.)
研究者
Mr Sandeep AV
AstraZeneca Pharma India Ltd
研究点 (10)
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