A Phase III, Randomized, Open-Label Study of Pralsetinib Versus Standard of Care for First-Line Treatment of RET Fusion-Positive, Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 223
- 试验地点
- 74
- 主要终点
- Arm A vs Arm B: Treatment Period: Progression-free Survival (PFS)
研究概览
简要总结
This is an international, randomized, open-label, Phase 3 study designed to evaluate whether the potent and selective RET inhibitor, pralsetinib, improves outcomes when compared to a platinum chemotherapy-based regimen chosen by the Investigator from a list of standard of care treatments, as measured primarily by progression free survival (PFS), for participants with RET fusion-positive metastatic NSCLC who have not previously received systemic anticancer therapy for metastatic disease.
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
- 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
- •Participant has pathologically confirmed, definitively diagnosed, locally advanced (not able to be treated with surgery or radiotherapy) or metastatic NSCLC and has not been treated with systemic anticancer therapy for metastatic disease.
- •Participant must have a documented RET-fusion
- •Participant has measurable disease based on RECIST 1.1 as determined by the local site Investigator/radiology assessment.
- •Participant has an ECOG Performance Status of 0 or
- •Participant should not have received any prior anticancer therapy for metastatic disease.
- •Participants can have received previous anticancer therapy (except a selective RET inhibitor) in the neoadjuvant or adjuvant setting but must have experienced an interval of at least ≥ 6 months from completion of therapy to recurrence.
- •Participants that received previous immune checkpoint inhibitors in the adjuvant or consolidation following chemoradiation are not allowed to receive pembrolizumab if randomized in Arm B
- •Participant is an appropriate candidate for and agrees to receive 1 of the Investigator choice platinum-based chemotherapy regimens if randomized to Arm B.
- •For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception.
- •For men: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use a condom and agree to refrain from donating sperm.
排除标准
- •Participant's tumor has any additional known primary driver alterations other than RET, such as targetable mutations of EGFR, ALK, ROS1, MET, and BRAF. Investigators should discuss enrollment with Sponsor designee regarding co-mutations.
- •Participant previously received treatment with a selective RET inhibitor.
- •Participant received radiotherapy or radiosurgery to any site within 14 days before randomization or more than 30 Gy of radiotherapy to the lung in the 6 months before randomization.
- •Participant with a history of pneumonitis within the last 12 months.
- •Participant has CNS metastases or a primary CNS tumor that is associated with progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease. If a participant requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks before Cycle 1 Day
- •Participant has had a history of another primary malignancy that has been diagnosed or required therapy within the past 3 years prior to randomization.
研究组 & 干预措施
Pralsetinib
Participants randomized to the Experimental Arm will receive Pralsetinib
干预措施: Pralsetinib (Drug)
Platinum-based chemotherapy with or without pembrolizumab
Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)
Nonsquamous histology
- Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
- Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
Squamous histology
- Carboplatin or cisplatin / gemcitabine
- Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab
干预措施: Carboplatin (Drug)
Platinum-based chemotherapy with or without pembrolizumab
Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)
Nonsquamous histology
- Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
- Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
Squamous histology
- Carboplatin or cisplatin / gemcitabine
- Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab
干预措施: Cisplatin (Drug)
Platinum-based chemotherapy with or without pembrolizumab
Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)
Nonsquamous histology
- Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
- Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
Squamous histology
- Carboplatin or cisplatin / gemcitabine
- Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab
干预措施: Pemetrexed (Drug)
Platinum-based chemotherapy with or without pembrolizumab
Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)
Nonsquamous histology
- Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
- Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
Squamous histology
- Carboplatin or cisplatin / gemcitabine
- Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab
干预措施: Pembrolizumab (Drug)
Platinum-based chemotherapy with or without pembrolizumab
Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)
Nonsquamous histology
- Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
- Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
Squamous histology
- Carboplatin or cisplatin / gemcitabine
- Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab
干预措施: Gemcitabine (Drug)
Platinum-based chemotherapy with or without pembrolizumab
Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)
Nonsquamous histology
- Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
- Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
Squamous histology
- Carboplatin or cisplatin / gemcitabine
- Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab
干预措施: Paclitaxel (Drug)
Platinum-based chemotherapy with or without pembrolizumab
Participants randomized to the Active Comparator Arm will receive 1 of 6 platinum-based chemotherapy treatment regimens (with or without pembrolizumab) at the study center as chosen by the treating Investigator (based on histology)
Nonsquamous histology
- Carboplatin or cisplatin / pemetrexed (with vitamin supplementation); with optional pemetrexed (with vitamin supplementation) maintenance.
- Pembrolizumab / carboplatin or cisplatin / pemetrexed (with vitamin supplementation); followed by pembrolizumab and optional pemetrexed (with vitamin supplementation) maintenance.
Squamous histology
- Carboplatin or cisplatin / gemcitabine
- Carboplatin with paclitaxel/nab-paclitaxel and pembrolizumab
干预措施: Nab-Paclitaxel (Drug)
结局指标
主要结局
Arm A vs Arm B: Treatment Period: Progression-free Survival (PFS)
时间窗: Up to approximately 50 months
PFS was defined as the time from randomization to the date of first documented PD as determined by the investigator with the use of Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm). Kaplan-Meier (K-M) method was used to estimate median PFS. 95% CI for median was computed using the method of Brookmeyer and Crowley.
次要结局
- Arm A vs Arm B: Objective Response Rate (ORR)(Up to approximately 50 months)
- Arm A vs Arm B: Overall Survival (OS)(From randomization to death (up to approximately 50 months))
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 50 months)
- Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score(Baseline up to 50 months)
- Arm A vs Arm B: Duration of Response (DOR)(Up to approximately 50 months)
- Arm A vs Arm B: Clinical Benefit Rate (CBR)(Up to approximately 50 months)
- Arm A vs Arm B: Disease Control Rate (DCR)(Up to approximately 50 months)