A Phase II, Randomized, Multicenter, Double-Blind, Controlled Study of Tobemstomig Plus Platinum-Based Chemotherapy Versus Pembrolizumab Plus Platinum-Based Chemotherapy in Patients With Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 182
- 试验地点
- 100
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tobemstomig (RO7247669) in combination with platinum-based chemotherapy compared with pembrolizumab plus platinum-based chemotherapy in participants with previously untreated, locally advanced, unresectable (Stage IIIB/IIIC) or metastatic (Stage IV) non-small-cell lung cancer (NSCLC) who are not eligible to receive curative surgery and/or definitive chemoradiotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Histologically or cytologically documented locally advanced, unresectable (Stage IIIB/IIIC) or metastatic (Stage IV) NSCLC who are not eligible for curative surgery and/or definitive chemoradiotherapy
- •No prior systemic treatment for metastatic NSCLC
- •Known tumor PD-L1 status
- •Confirmed availability of representative tumor specimens
- •Measurable disease
- •Life expectancy of at least 12 weeks
- •Adequate hematologic and end-organ function
- •Negative for HIV, hepatitis B (HBV), and hepatitis C (HCV)
- •Adequate cardiovascular function
排除标准
- •NSCLC known to have a mutation in the EGFR gene or an ALK fusion oncogene
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Untreated or clinically unstable spinal cord confession
- •History of leptomeningeal disease
- •Uncontrolled tumor-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)
- •Uncontrolled or symptomatic hypercalcemia
- •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, granulomatosis with polyangiitis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with exceptions defined by the protocol
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography (CT) scan
- •Active tuberculosis (TB) or untreated latent TB
- •Current treatment with anti-viral therapy for HBV or HCV
- •Significant cardiovascular disease within 3 months prior to randomization
- •Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- •History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death e.g., 5-year OS] rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
- •Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could affect patient safety
- •Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- •Prior allogeneic stem cell or solid organ transplantation
- •Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- •Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
- •Treatment with investigational therapy within 28 days prior to initiation of study treatment
- •Any anti-cancer therapy, including hormonal therapy, within 21 days prior to initiation of study treatment
- •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including, but not limited to, anti-cytotoxic T lymphocyte-associated protein 4, anti-T cell immunoreceptor with Ig and tyrosine-based inhibition motif domains, anti-PD-1 and anti-PD-L1 therapeutic antibodies, and anti-LAG3) agents
- •Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks or 5 drug-elimination half lives (whichever is longer) prior to initiation of study treatment
- •Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
- •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies, fusion proteins, or platinum-containing compounds
- •Known hypersensitivity to Chinese hamster ovary cell products or to any component of the tobemstomig or pembrolizumab formulation
- •Known allergy or hypersensitivity or other contraindication to any component of the chemotherapy regimen the patient may receive during the study
- •Pregnancy or breastfeeding
研究组 & 干预措施
Arm B: Pembrolizumab + Platinum-Based Chemotherapy
Participants with NSQ NSCLC will receive induction treatment with blinded pembrolizumab in combination with pemetrexed and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by a maintenance therapy with blinded pembrolizumab together with pemetrexed Q3W until disease progression or treatment discontinuation.
Participants with SQ NSCLC will receive blinded pembrolizumab in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by blinded pembrolizumab (on Day 1) Q3W until disease progression or treatment discontinuation.
干预措施: Carboplatin (Drug)
Arm A: Tobemstomig + Platinum-Based Chemotherapy
Participants with non-squamous (NSQ) NSCLC will receive induction treatment with blinded tobemstomig in combination with pemetrexed and carboplatin, all on Day 1 every 3 weeks (Q3W) for four 21-day cycles, followed by Q3W maintenance therapy with blinded tobemstomig together with pemetrexed until disease progression or treatment discontinuation.
Participants with squamous (SQ) NSCLC will receive blinded tobemstomig in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21 day cycles, followed by blinded tobemstomig (on Day 1) Q3W until disease progression or treatment discontinuation.
干预措施: Tobemstomig (Drug)
Arm B: Pembrolizumab + Platinum-Based Chemotherapy
Participants with NSQ NSCLC will receive induction treatment with blinded pembrolizumab in combination with pemetrexed and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by a maintenance therapy with blinded pembrolizumab together with pemetrexed Q3W until disease progression or treatment discontinuation.
Participants with SQ NSCLC will receive blinded pembrolizumab in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by blinded pembrolizumab (on Day 1) Q3W until disease progression or treatment discontinuation.
干预措施: Pemetrexed (Drug)
Arm A: Tobemstomig + Platinum-Based Chemotherapy
Participants with non-squamous (NSQ) NSCLC will receive induction treatment with blinded tobemstomig in combination with pemetrexed and carboplatin, all on Day 1 every 3 weeks (Q3W) for four 21-day cycles, followed by Q3W maintenance therapy with blinded tobemstomig together with pemetrexed until disease progression or treatment discontinuation.
Participants with squamous (SQ) NSCLC will receive blinded tobemstomig in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21 day cycles, followed by blinded tobemstomig (on Day 1) Q3W until disease progression or treatment discontinuation.
干预措施: Paclitaxel (Drug)
Arm A: Tobemstomig + Platinum-Based Chemotherapy
Participants with non-squamous (NSQ) NSCLC will receive induction treatment with blinded tobemstomig in combination with pemetrexed and carboplatin, all on Day 1 every 3 weeks (Q3W) for four 21-day cycles, followed by Q3W maintenance therapy with blinded tobemstomig together with pemetrexed until disease progression or treatment discontinuation.
Participants with squamous (SQ) NSCLC will receive blinded tobemstomig in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21 day cycles, followed by blinded tobemstomig (on Day 1) Q3W until disease progression or treatment discontinuation.
干预措施: Carboplatin (Drug)
Arm A: Tobemstomig + Platinum-Based Chemotherapy
Participants with non-squamous (NSQ) NSCLC will receive induction treatment with blinded tobemstomig in combination with pemetrexed and carboplatin, all on Day 1 every 3 weeks (Q3W) for four 21-day cycles, followed by Q3W maintenance therapy with blinded tobemstomig together with pemetrexed until disease progression or treatment discontinuation.
Participants with squamous (SQ) NSCLC will receive blinded tobemstomig in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21 day cycles, followed by blinded tobemstomig (on Day 1) Q3W until disease progression or treatment discontinuation.
干预措施: Pemetrexed (Drug)
Arm B: Pembrolizumab + Platinum-Based Chemotherapy
Participants with NSQ NSCLC will receive induction treatment with blinded pembrolizumab in combination with pemetrexed and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by a maintenance therapy with blinded pembrolizumab together with pemetrexed Q3W until disease progression or treatment discontinuation.
Participants with SQ NSCLC will receive blinded pembrolizumab in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by blinded pembrolizumab (on Day 1) Q3W until disease progression or treatment discontinuation.
干预措施: Pembrolizumab (Drug)
Arm B: Pembrolizumab + Platinum-Based Chemotherapy
Participants with NSQ NSCLC will receive induction treatment with blinded pembrolizumab in combination with pemetrexed and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by a maintenance therapy with blinded pembrolizumab together with pemetrexed Q3W until disease progression or treatment discontinuation.
Participants with SQ NSCLC will receive blinded pembrolizumab in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by blinded pembrolizumab (on Day 1) Q3W until disease progression or treatment discontinuation.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Randomization to date of first documented disease progression or death (up to approximately 15 months)
PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Progression-Free Survival (PFS)
时间窗: Randomization to date of first documented disease progression or death (up to approximately 15 months)
PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Objective Response Rate (ORR)
时间窗: Up to approximately 15 months
ORR is defined as the percentage of participants who experience a complete reponse or partial response on two consecutive occasions at least 4 weeks apart as determined by the investigator according to RECIST v1.1.
次要结局
- Duration of Response (DOR)(From the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first) (up to approximately 15 months))
- PFS in Participants With PD-L1 Expression(Up to 28 months)
- OS for Participants With PD-L1 Expression(Up to 28 months)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Tired(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Aches/Pain in Bones(Baseline to week 12)
- Number of Participants With Adverse Events (AEs)(From the start of treatment to 90 days after the final dose of treatment (up to 28 months))
- Maximum Serum Concentration (Cmax) of Tobemstomig(Up to approximately 15 months)
- Time of Maximum Concentration (Tmax) of Tobemstomig(Up to approximately 15 months)
- Volume of Distribution at Steady State (Vss) of Tobemstomig(Up to approximately 15 months)
- Half-life (T1/2) of Tobemstomig(Up to approximately 15 months)
- Percentage of Participants With Anti-drug Antibodies (ADAs)(Baseline up to approximately 15 months)
- Overall Survival (OS)(From randomization to death from any cause (up to approximately 15 months))
- Change in Participant-reported Outcomes as Assessed by the European Organisation for Research and Treatment (EORTC): Physical Functioning(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Global Health Status/Quality of Life (GHS/QoL)(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Role Functioning(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Lung Cancer Symptoms/How Much Did You Cough(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath When Rested(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath When Walked(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath Climbed Stairs(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Pain in Chest(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Need to Rest(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Felt Weak(Baseline to week 12)
- Percentage of Participants With Anti-drug Antibodies (ADAs)(Baseline up to approximately 15 months)
- Overall Survival (OS)(From randomization to death from any cause (up to approximately 15 months))
- Duration of Response (DOR)(From the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first) (up to approximately 15 months))
- PFS in Participants With PD-L1 Expression(Up to 28 months)
- OS for Participants With PD-L1 Expression(Up to 28 months)
- Change in Participant-reported Outcomes as Assessed by the European Organisation for Research and Treatment (EORTC): Physical Functioning(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Global Health Status/Quality of Life (GHS/QoL)(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Role Functioning(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Lung Cancer Symptoms/How Much Did You Cough(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath When Rested(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath When Walked(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Short of Breath Climbed Stairs(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Pain in Chest(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Need to Rest(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Felt Weak(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Tired(Baseline to week 12)
- Change in Participant-reported Outcomes as Assessed by the EORTC: Aches/Pain in Bones(Baseline to week 12)
- Number of Participants With Adverse Events (AEs)(From the start of treatment to 90 days after the final dose of treatment (up to 28 months))
- Maximum Serum Concentration (Cmax) of Tobemstomig(Up to approximately 15 months)
- Time of Maximum Concentration (Tmax) of Tobemstomig(Up to approximately 15 months)
- Clearance (CL) of Tobemstomig(Up to approximately 15 months)
- Volume of Distribution at Steady State (Vss) of Tobemstomig(Up to approximately 15 months)
- Area Under the Concentration-time Curve (AUC) of Tobemstomig(Up to approximately 15 months)
- Half-life (T1/2) of Tobemstomig(Up to approximately 15 months)