A Phase Ib/II Open-Label, Multicentre Platform Study Evaluating Novel Combinations in Participants with Advanced or Metastatic Non-Small Cell Lung Cancer (ALTAIR)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 55
- 试验地点
- 34
- 主要终点
- Part A: Safety run-in. Safety and tolerability will be evaluated in terms of DLT (to determine the recommended dose), AEs/SAEs, imAEs, AEs leading to discontinuation, laboratory findings, ECGs, vital signs, and physical examinations.The estimates of interest are:-Incidence of AEs/SAEs, imAEs, and AEs leading to discontinuation -Incidence of DLTs-Mean changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination.
研究概览
简要总结
Part A: Safety run- in To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents. Part B: Dose expansion To assess the safety and tolerability of the combination of novel anti-cancer agents To estimate the anti-tumour activity of the combination of novel anti-cancer agents
研究设计
- 分配方式
- Na
- 主要目的
- This is a Phase Ib/II, multicentre, open-label platform study evaluating novel combination
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥ 18 years of age at the time of signing the informed consent.
- •Capable of giving signed informed consent
- •Provision of signed and dated informed consent prior to any mandatory study-specific procedures, sampling and analysis
- •Participant is willing and able to comply with the study protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- •Participants with histologically or cytologically documented squamous or non-squamous NSCLC.
- •With a current Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
- •WHO/ECOG performance status of 0 or 1 at screening
- •Measurable disease per RECIST
- •Minimum life expectancy of 12 weeks in the opinion of the investigator
- •Adequate organ and marrow function
- •Contraceptive use by male or female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- •Female participants of child-bearing potential: (i) Must have negative pregnancy test at screening and within 3 days prior to each administration of study intervention. (ii) If sexually active with a non-sterilised male partner, must agree to use one highly effective method of birth control from enrolment throughout the study and after last dose of study intervention as specified in each sub-study. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, spermicides only, and lactational amenorrhea method are not acceptable. Female condom and male condom should not be used together. (iii) Must not breastfeed and must not donate, or retrieve for their own use, ova from screening to after the last dose of study intervention
排除标准
- •Participants with any of the following are excluded: (a) Sensitising EGFR mutations or ALK fusions (documented test result is mandatory for participants with non-squamous histology). For participants with squamous histology mutation/fusion, testing is mandatory only if participant is a never smoker or in the presence of a mixed histology. (b) Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (eg, ROS1, NTRK fusions, BRAF V600E mutation, etc).(c) Presence of small cell and neuroendocrine histology components.(d) Has locally advanced unresectable Stage III disease (see specific sub-study for the number of allowed prior lines of therapy).
- •Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
- •As judged by the investigator, any severe or uncontrolled systemic diseases, including, but not limited to, uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; interstitial lung disease/pneumonitis (of any grade); unstable and/or symptomatic venous thromboembolism, serious chronic gastrointestinal conditions associated with diarrhoea active non-infectious skin disease, psychiatric illness/social situations, substance abuse, or significant conditions which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol
- •Previous enrolment in the present study.
- •For females only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding or planning to become pregnant.
- •Has had a prior stem cell, bone marrow, allogenic tissue, or solid organ transplant.
- •History of another primary malignancy except for 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. Exceptions include adequately resected non-melanoma skin cancer, localised non-invasive primary disease under surveillance and curatively treated in situ disease.
- •History of clinically significant arrhythmia, cardiomyopathy of any aetiology; symptomatic congestive heart failure (as defined by New York Heart Association class ≥ 3), history of myocardial infarction within the past 6 months.
- •Has an active autoimmune disease that has required systemic treatment in the past 5 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
- •Spinal cord compression.
- •Persistent toxicities (CTCAE ≥ Grade 2 caused by previous anti-cancer therapy excluding alopecia. (a) Participants who have the following chronic, stable Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to study intervention and managed with standard of care treatment) which the investigator deems related to previous anti-cancer therapy can be included: (i)Chemotherapy-induced neuropathy (ii)Fatigue (iii)Vitiligo (iv) Endocrine disorders that are controlled with replacement hormone therapy). (v) Irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator (eg, hearing loss)
- •Symptomatic brain metastases. Note: participants potentially are eligible with known asymptomatic CNS lesions that do not require local treatment according to principal investigator, or asymptomatic, adequately treated with stereotactic radiation therapy, craniotomy, gamma knife therapy, or whole brain radiotherapy, with no subsequent evidence of CNS progression. Participants must not require steroids or anticonvulsants for at least 4 weeks prior to start of study . A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and enrolment. Participants must have recovered from the acute toxic effect of radiotherapy
- •Treatment with any of the following agents and interventions: (a) Any other anti-cancer agents within the following time periods prior to the first dose of study intervention (see specific sub-study for prior agents that are excluded): (i)Cytotoxic treatment: 21 days. (ii)Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter). (iii)Biological products including immuno-oncology agents: 28 days. (b)Any investigational agents or study interventions from a previous clinical study: 28 days or 5 half-lives (whichever is shorter). (c)Immunosuppressive medication: except (i)Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection). (ii)Systemic corticosteroids at physiological doses not to exceed 10 mg/day of prednisone or equivalent. (iii)Steroids as premedication for hypersensitivity reactions
- •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. Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A minimum of one week is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
- •Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study. Note: Local surgery of isolated lesions for palliative intent is acceptable.
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Participants should not receive live vaccine while receiving study intervention and up to 30 days after the last dose of study intervention. COVID-19 vaccination should not be given for 72 hours prior to administration of the first dose of study intervention.
- •Participation in another clinical study with a study intervention administered in the last 12 months or the combination/comparator agent (unless the safety profile is known prior to enrolment).
- •Judgement by the investigator that the individual should not participate in the study.
- •Concurrent enrolment into another interventional clinical trial, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
研究组 & 干预措施
Rilvegostomig
干预措施: Rilvegostomig (Drug)
Cyramza 10 mg/ml concentrate for solution for infusion, Cyramza 10 mg/ml concentrate for solution for infusion, Cyramza 10 mg/ml concentrate for solution for infusion
干预措施: Cyramza 10 mg/ml concentrate for solution for infusion (Drug)
结局指标
主要结局
Part A: Safety run-in. Safety and tolerability will be evaluated in terms of DLT (to determine the recommended dose), AEs/SAEs, imAEs, AEs leading to discontinuation, laboratory findings, ECGs, vital signs, and physical examinations.The estimates of interest are:-Incidence of AEs/SAEs, imAEs, and AEs leading to discontinuation -Incidence of DLTs-Mean changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination.
Part A: Safety run-in. Safety and tolerability will be evaluated in terms of DLT (to determine the recommended dose), AEs/SAEs, imAEs, AEs leading to discontinuation, laboratory findings, ECGs, vital signs, and physical examinations.The estimates of interest are:-Incidence of AEs/SAEs, imAEs, and AEs leading to discontinuation -Incidence of DLTs-Mean changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination.
Part B: Dose expansion Safety and tolerability will be evaluated in terms of AEs/SAEs, imAEs, AEs leading to discontinuation, laboratory findings, ECGs, vital signs, and physical examinations.The estimates of interest are:Incidence of AEs/SAEs, imAEs, and AEs leading to discontinuation.Mean changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination.
Part B: Dose expansion Safety and tolerability will be evaluated in terms of AEs/SAEs, imAEs, AEs leading to discontinuation, laboratory findings, ECGs, vital signs, and physical examinations.The estimates of interest are:Incidence of AEs/SAEs, imAEs, and AEs leading to discontinuation.Mean changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination.
Part B: Dose expansion :Objective response is defined as BOR of confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST1.1. The estimate of interest is • OR The analysis will include participants in the Response Evaluable Analysis Set. Participants will be analyzed according to their planned treatment and indication
Part B: Dose expansion :Objective response is defined as BOR of confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST1.1. The estimate of interest is • OR The analysis will include participants in the Response Evaluable Analysis Set. Participants will be analyzed according to their planned treatment and indication
次要结局
- Part A: Safety run-in • OR • DOR, TTR, DC • PFS and OS
- Part B: Dose expansion :•DOR, TTR, DC (similar to Part A efficacy) •PFS (similar to Part A efficacy) •OS (similar to Part A efficacy)
- All parts of the study :Serum concentrations and derived PK parameters of novel agents
- All parts of the study:Incidence of ADAs against novel agents in serum
研究者
AstraZeneca Clinical Study Information Centre
Scientific
AstraZeneca AB