CTRI/2024/10/075886招募中3 期
A Phase III, Randomised, Open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig (AZD2936) or Rilvegostomig Monotherapy Versus Pembrolizumab Monotherapy for the First-line Treatment of Participants With Locally-advanced or Metastatic Non-squamous NSCLC With High PD-L1 Expression (TC greeter than or equal to 50 percentage) and Without Actionable Genomic Alterations (TROPION-Lung10)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 675
- 试验地点
- 11
- 主要终点
- Progression Free Survival (PFS) assessed by BICR (Blinded Independent Central Review) for Arm 1 Vs Arm 2
研究概览
简要总结
A Phase III, Open-label, Randomised Study of assessing the efficacy and safety of Dato-DXd in combination with rilvegostomig compared with pembrolizumab for first-line treatment of participants with locally-advanced or metastatic non’squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations(Tropion Lung 10). The target population of interest in this study is participants ≥ 18 years with PD’L1 positive locally-advanced or metastatic non’squamous NSCLC.Participants must not have received prior treatment of NSCLC, no prior immunotherapy or immunosuppressive medicines. Approximately 2300 participants with Non-squamous NSCLC will be screened/enrolled to achieve approximately 675 participants randomised to study intervention. Participants will be randomised either in the ratio of 2:1:2 in Arm 1 (DtatoDXD + Rilvegostomig), Arm 2(Rilvegostomig monotherapy and Arm 3(Pembrolizumab monotherapy) All participants in Arm 1 and Arm 2 , will receive study intervention until investigator-assessed progression of disease (PD) according to RECIST 1.1, or until unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met. Participants on Arm 3 will receive Inj Pembrolizumab until disease progression, unacceptable toxicity, the participant requests to stop the study treatment, or other specific discontinuation criteria are met, with a maximum of 35 cycles/24 months. Cross over between the arms in not allowed.
Follow-up of participants post discontinuation of study intervention:
After study treatment discontinuation, all participants will undergo an end-of-treatment visit and safety follow up visits at protocol defined period
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 Age 1 Participant must be ≥ 18 years, at the time of signing the ICF.
- •Type of Participant and Disease Characteristics 2 All races, gender and ethnic groups are eligible for this study.
- •3 Histologically or cytologically documented non squamous NSCLC.
- •4 Stage IIIB or IIIC or Stage IV metastatic NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.
- •5 Absence of sensitising EGFR mutations (including, but not limited to, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), and ALK and ROS1 rearrangements.
- •6 Absence of documented tumour 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.
- •7 ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to the first dose of study intervention.
- •8 Minimum life expectancy of 12 weeks.
- •9 Provision of acceptable FFPE tumour sample from a lesion not previously irradiated.
- •10 Known tumour PD-L1 expression status defined as TC ≥ 50%, determined prospectively using the VENTANA PD-L1 (SP263) Assay by a Sponsor-designated central laboratory 11 Prior to the availability of the TROP2 assay, participants must provide tumour material for retrospective testing to be eligible for the study.
- •12 At least one lesion not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline and can be accurately measured at baseline.
- •13 Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention defined as: Weight 14 Body weight ≥ 30 kg at screening and randomisation.
- •Sex and Contraceptive/Barrier Requirements 15 Male and female.
- •Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •16 All females of child-bearing potential must have a negative serum pregnancy test result during the study screening period Informed Consent 17 Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this CSP.
- •18 Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative.
排除标准
- •Exclusion Criteria Participants are excluded from the study if any of the following criteria apply Medical Conditions 1 As judged by the investigator, any evidence of diseases or history of allogenic organ transplant, 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.
- •2 History of another primary malignancy.
- •3 Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small cell lung cancer; NSCLC histology, sarcomatoid variant.
- •4 Persistent toxicities caused by previous anti-cancer therapy with some exceptions 5 Active or prior documented autoimmune or inflammatory disorders, with few exceptions.
- •6 Known spinal cord compression.
- •7 Brain metastases unless participant treated and no longer symptomatic, radiologically stable, and who require no treatment with corticosteroids or anticonvulsants.
- •8 Thromboembolic event within 3 months of the first dose of study intervention.
- •9 Known leptomeningeal carcinomatosis.
- •10 Has clinically significant third-space fluid retention and is not amenable for repeated drainage 11 Known clinically significant corneal disease.
- •12 Has active or uncontrolled hepatitis B or C virus infection.
- •Note: Participants with active Hepatitis A are not eligible for this study 13 History of active primary immunodeficiency 14 Known HIV infection that is not well controlled.
- •15 Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).
- •16 Known to have active tuberculosis infection 17 Resting ECG with clinically abnormal findings or participant meets one or more of the following (a) Mean resting corrected QT interval 470 ms, regardless of gender obtained from triplicate 12-lead ECGs performed at screening.
- •(b) History of QT prolongation associated with other medications that required discontinuation of that medication.
- •(c) Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
- •18 Uncontrolled or significant cardiac disease 19 History of non-infectious ILD/pneumonitis.
- •20 Has severe pulmonary function compromise resulting 21 Is currently pregnant, breastfeeding, planning to become pregnant or father children within the projected duration of the study Prior Concomitant Therapy 22 Participants who have received prior systemic therapy for advanced/metastatic NSCLC.
- •23 Prior exposure to chloroquine hydroxychloroquine without an adequate treatment washout period of 14 days before randomisation 24 Prior exposure to: (a) An anti-TIGIT therapy, anti-PD-1, anti-PD-L1 therapy or an antibody targeting any other immuno-regulatory receptors or mechanisms, including combinations and combined agents.
- •(b) Therapeutic anti-cancer vaccines.
- •(d) TROP2-targeted therapy 25 Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention, with exceptions 26 Any concurrent anti-cancer treatment.
- •27 Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention.
- •28 Palliative radiation 29 Major surgical procedure or significant traumatic injury within 3 weeks of randomisation or an anticipated need for major surgery during the study.
- •Prior/Concurrent Clinical Study Experience 30 Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 12 months prior to first dose of study intervention 31 Participants with a known history of severe hypersensitivity reactions to either Dato-DXd, rilvegostomig or pembrolizumab or any excipients of Dato-DXd, rilvegostomig or pembrolizumab including but not limited to polysorbate
- •32 Participants with a known history of severe hypersensitivity reactions to other monoclonal antibodies.
- •Other Exclusions 33 Involvement in the planning and/or conduct of the study 34 Judgment 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.
- •Previous randomisation in the present study.
结局指标
主要结局
Progression Free Survival (PFS) assessed by BICR (Blinded Independent Central Review) for Arm 1 Vs Arm 2
时间窗: Progression Free Survival (PFS) assessed by BICR (Blinded Independent Central Review) for Arm 1 Vs Arm 2 | Imaging assessments : Every 6 weeks (± 7 days) up to Week 12, then every 9 weeks (± 7 days) up to Week 57 and then every 12 weeks (± 7 days) thereafter, relative to the date of randomisation and until RECIST 1.1-defined radiological PD plus an additional follow-up scan at least 4 weeks later and no later than the next scheduled imaging visit
次要结局
- Progression Free Survival (PFS) by Blinded Independent Clinical Review (BICR) in TROP2 biomarker positive participants for Arm 1 and Arm 3(PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR, or death due to any cause)
- Progression Free Survival (PFS) by Blinded Independent Clinical Review (BICR) in the (Intent to treat ) ITT population(PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR, or death due to any cause)
- To demonstrate the superiority of Dato-DXd in combination with rilvegostomig relative to pembrolizumab by assessment of OS in the ITT population..(OS is defined as the time from randomisation until the date of death due to any cause.)
- To demonstrate the superiority of Dato DXd in combination with rilvegostomig relative to pembrolizumab by assessment of ORR.(ORR is defined as the proportion of participants who have a CR or PR, as determined by BICR per RECIST 1.1.)
- To estimate the effectiveness of Dato DXd in combination with rilvegostomig relative to pembrolizumab by assessment of DoR.(DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR and investigator assessment or death due to any cause.)
- To estimate the effectiveness of rilvegostomig versus pembrolizumab.(All the above endpoints will be repeated for rilvegostomig versus pembrolizuma)
- To estimate the effectiveness of Dato-DXd in combination with rilvegostomig versus rilvegostomig.(All the above endpoints will be repeated for Dato-DXd in combination with rilvegostomig versus rilvegostomig.)
- To assess participant-reported lung cancer symptoms of NSCLC in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab.(Time to deterioration in pulmonary symptoms (dyspnoea, cough, and chest pain) as measured by the NSCLC-SAQ.)
- To assess participant-reported physical functioning in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab.(Time to deterioration in physical functioning as measured by PROMIS Physical Function short form 8c.)
- To assess participant-reported GHS/QoL of life in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab(Time to deterioration in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172)
- To assess the PK of Dato-DXd when combined with rilvegostomig, as well as the PK of rilvegostomig.(Concentration of rilvegostomig, Dato-DXd, total anti TROP2 antibody, and MAAA 1181a (payload deruxtecan) in plasma or serum and PK parameters (peak and trough concentrations).)
- To investigate the immunogenicity of Dato DXd and rilvegostomig in combination therapy and rilvegostomig monotherapy.(Presence of ADA for Dato-DXd and rilvegostomig (confirmatory results, titres and neutralising antibodies for confirmed positive samples))
- To demonstrate the superiority of Dato DXd in combination with rilvegostomig relative to pembrolizumab by assessment of PFS2.(PFS2 is defined as the time from randomisation to the earliest of the progression events (following the initial progression), subsequent to first subsequent therapy, or death.)
- To assess the safety and tolerability of Dato DXd in combination with rilvegostomig and rilvegostomig monotherapy as compared with pembrolizumab.(Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE Version 5.0), rates of AE-related dose discontinuations and modifications, and also in terms of:)
研究者
Mr Sandeep AV
AstraZeneca Pharma India Ltd
研究点 (11)
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